Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, moderate, severe, subcutaneous, Olokizumab, open-label
Brief summary
The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3 (core studies). The long-term efficacy, immunogenicity, the physical function and quality of life of subjects received long-term treatment with OKZ were assessed as well.
Detailed description
This OLE study (CL04041024) included an 82-week open-label Treatment Period that followed completion of one of the core studies (Study CREDO 1, 2 or 3). The OLE open-label Treatment Period lasted from Visit 1 (OLE Baseline/Week 24) to Visit 10 (End of Treatment (EoT)/Week 106), followed by a 20-week Safety Follow-Up Period from Week 106 to Week 126. The first visit of the OLE study was the same visit as the Week 24 visit in the core studies. Subjects were randomized to 1 of the 2 OKZ treatment groups in the OLE study based on the treatment received in the core studies. Subjects who had received OKZ (q2w or q4w) in the core study in which they had participated (including subjects who received placebo in Study CREDO 3 and were re-randomized to OKZ at Week 16) received the same OKZ treatment regimen in the OLE study. Subjects who had received placebo (Study CREDO 1 and CREDO 2) or adalimumab (Study CREDO 2) in the core study in which they had participated were randomized in a 1:1 ratio to OKZ 64 mg q2w or OKZ 64 mg q4w regimens in the OLE study. For the first 12 weeks of the OLE, all subjects were required to remain on a stable dose of background methotrexate (MTX) at 15 to 25 mg/week (or≥10 mg/week if there was documented intolerance to higher doses) with a stable route of administration (oral, SC, or intramuscular (IM)). After 12 weeks (Visit 4 \[Week 36\] of the OLE study), the Investigator might adjust the MTX dosage and route, per local guidelines. Methotrexate might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study. Subjects who had been on rescue disease-modifying anti-rheumatic drugs (DMARDs) during the core studies were asked to continue these medications for the first 12 weeks of the OLE study. The Investigator could adjust these background medications if deemed appropriate after Visit 4 (Week 36) of the OLE study. Background rescue therapy might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study. Throughout the study, concomitant treatment with folic acid ≥ 5 mg per week or equivalent was required for all subjects. Subjects returned to the study site periodically for safety and response assessments as per the Schedule of Events. The last dose of open-label study treatment in the OLE study was administered at Week 104 for all subjects. After completion of the 82-week open-label Treatment Period, subjects entered the 20-week Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for 3 visits at +4, +8, and +22 weeks after the last dose of study treatment. Subjects who discontinued the open-label treatment prematurely required to come for the EoT Visit 2 weeks after the last study treatment administration and then return for the 3 Safety Follow-Up Visits +4, +8, and +22 weeks after the last study treatment administration. Adverse events were assessed throughout the study period and evaluated using the Common Technology Criteria version 4.0 (CTCAE v 4.0). There were ongoing monitoring of safety events, including laboratory findings by the Sponsor or its designee. In addition, safety parameters were assessed throughout the study by an independent Data Safety Monitoring Board (DSMB).
Interventions
DRUGOlokizumab 64 mg SC q4w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS).PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.
DRUGOlokizumab 64 mg SC q2w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.
DRUGConcomitant treatment
Methotrexate 15 to 25 mg/week (or ≥ 10 mg/week if there was documented intolerance to higher doses). (Subject maintained their stable dose and route (oral, SC, or IM) during the core study and for ≥ 12 additional weeks of OLE.) Folic acid ≥ 5 mg per week or equivalent
Sponsors
IQVIA Pvt. Ltd
OCT Clinical Trials
R-Pharm International, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects may be enrolled in the study only if they meet all of the following criteria: 1. Subject must be willing and able to sign informed consent 2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025). 3. Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for ≥ 12 additional weeks 4. Subjects must be willing to take folic acid or equivalent throughout the study.
Exclusion criteria
1. Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent Adverse events (AEs) or serious adverse events (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement. 2. Subject has evidence of active tuberculosis (TB) 3. Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study \- Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment: 1. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice); 2. The subject starts prophylaxis for latent TB infection (LTBI) according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and 3. The subject is willing to complete the entire course of recommended LTBI therapy. 4. Subject has planned surgery during the first 12 weeks of the OLE study 5. Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug 6. Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status \[e.g., correlative age\] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels \>40 mIU/mL and estradiol \<20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment OR Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment. Highly effective contraception is defined as: * Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first dose of study treatment in the core study * In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by documented follow-up hormone level assessment * Total abstinence if it is the preferred and constant lifestyle of the subject. Thus, periodic abstinence such as ovulation, symptothermal, postovulation, calendar methods, and withdrawal are not acceptable methods of contraception. * Male sterilization surgery: at least 6 months prior to the first dose of study treatment in the core study (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female subjects, the vasectomized male should be the only partner. * Placement of established intrauterine device (IUD): IUD copper or IUD with progesterone * Barrier method (condom and intravaginal spermicide, cervical caps with spermicide, or diaphragm with spermicide) in combination with the following: established oral, injected, or implanted hormone methods of contraception or contraceptive patch. 7. Subject is unwilling or unable to follow the procedures outlined in the protocol. 8. Other medical or psychiatric conditions, or laboratory abnormalities that may increase the potential risk associated with study participation and administration of the study treatment, or that may affect study results interpretation and, as per Investigator's judgement, make the subject ineligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | up to Week 126 | Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term |
| Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | up to Week 126 | Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term. Deaths are included. |
| Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | up to Week 126 | — |
| Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment | up to Week 126 | — |
| Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure | up to Week 126 | Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments. |
| Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure | up to Week 126 | Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments. |
| Incidence Rate of Treatment Emergent AESIs (Safety Population) | up to Week 126 | Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Core baseline, Week 28 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Core baseline, Week 40 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Core baseline, Week 52 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | up to Week 82 | Number and Proportion of subjects achieving an ACR20 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥20% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP) |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Core baseline, Week 82 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | up to week 82 | The number and proportion of subjects with HAQ-DI improvement ≥ 0.22 Against OLE Baseline. HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | up to week 82 | CDAI Range: 0 (the best outcome) - 76 (the worst outcome), with a decrease from baseline indicating improvement. The CDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: CDAI = SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS) |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Core baseline, Week 64 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | up to Week 82 | Number and Proportion of subjects achieving an ACR50 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82 American College of Rheumatology 50 % response is a composite defined as a ≥ 50% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 50% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP) |
| American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | up to Week 82 | Number and Proportion of subjects achieving an ACR70 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82 American College of Rheumatology 70 % response is a composite defined as a ≥ 70% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 70% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP) |
| Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | up to week 82 | The number and proportion of subjects with SDAI score ≤ 3.3 (considered to be in remission). The SDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), CRP (mg/dL), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS) + CRP (mg/dL) |
| Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | up to Week 82 | Number and Proportion of subjects with DAS28 low disease activity (based on DAS28 C-reactive protein (CRP) \< 3.2), who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82. The DAS28 (CRP) was calculated in the statistical database for analysis purposes using the Swollen joint count (SJC) (28 joints), Tender joint count (TJC) (28 joints), CRP level, and the Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) (100 mm VAS, where 0 is no disease activity and 100 was maximal disease activity) according to the following formula: \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.36 × natural log (CRP+1)\] + \[0.014 × VAS\] + 0.96. |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Core baseline, Week 12 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
| Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Core baseline, Week 20 | HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. |
Countries
Argentina, Belarus, Brazil, Bulgaria, Colombia, Czechia, Estonia, Germany, Hungary, Latvia, Lithuania, Mexico, Poland, Russia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Enrollment was conducted at 241 sites in 18 countries (Argentina, Belarus, Bulgaria, Brazil, Colombia, Czech Republic, Germany, Estonia, United Kingdom, Hungary, South Korea, Lithuania, Latvia, Mexico, Poland, Russia, Taiwan, United States). A total of 2105 subjects who had previously completed 24 weeks of double-blind treatment in a core study were randomized. All except one randomized subject received OKZ treatment. A total of 2104 subjects were analyzed for efficacy in the mITT Population.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Olokizumab 64 mg SC q4w: 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL. | 1,057 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Olokizumab 64 mg SC q2w: 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL. | 1,047 |
| Total | 2,104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Compliance With Medication | 0 | 1 |
| Overall Study | Covid-19 | 43 | 34 |
| Overall Study | Death | 13 | 13 |
| Overall Study | Due To The Death Of His Wife, He Refused To Participate In Follow Up 3 | 0 | 1 |
| Overall Study | Follow Up Visit Not Performed (Patient Outside Residence) | 0 | 2 |
| Overall Study | Lack Of Discipline In Adhering To The Schedule Of Visits, Difficult Cooperation With The Patient | 1 | 0 |
| Overall Study | Lack Of Efficacy (PI Perspective) End Of Study Visit | 0 | 1 |
| Overall Study | Lost to Follow-up | 23 | 13 |
| Overall Study | Other: Adverse Event | 0 | 1 |
| Overall Study | Other: Protocol Violation (Refused From SFU Visits) | 0 | 1 |
| Overall Study | Patient Completed The Treatment, But Could Not Come For Follow-Up Visits Due To Another City Moving | 1 | 0 |
| Overall Study | Patient Moved Out Of Residence And was Not Able To Come To The Site | 1 | 3 |
| Overall Study | Patient Was Hospitalized Due To The SAE And Couldn't Visit The Site For Sfu-3 | 1 | 0 |
| Overall Study | Personal Reasons | 0 | 1 |
| Overall Study | PI Did Not Feel It Was Best For Subject To Be Without Treatment For 12 Weeks. | 0 | 1 |
| Overall Study | PI Terminated Subject From IP (Ae's Abnormal Wbc, Abnormal Absolute Neutrophils Lab) | 1 | 0 |
| Overall Study | Principal Investigator (PI) Decision, The PI Starting Subject On Another Biologic Medication | 0 | 1 |
| Overall Study | randomized in error | 1 | 0 |
| Overall Study | Safety Follow-Up Visit (SFU)-3 Was Performed By Phone Due To Family Reasons | 1 | 0 |
| Overall Study | Site was closed | 2 | 3 |
| Overall Study | Study Coordinator Error, Patient Started A Biologic And Study Coordinator Forgot To Complete SFU | 1 | 0 |
| Overall Study | Study Terminated By Principal Investigator | 0 | 1 |
| Overall Study | Subject Has A Severe Or Life Threatening Infection That Requires Hospitalization Per Medical Monitor | 0 | 1 |
| Overall Study | Subject Refusal To Attend Visit | 0 | 1 |
| Overall Study | Withdrawal by Subject | 139 | 124 |
Baseline characteristics
| Characteristic | Treatment Arm 2: OKZ 64 mg q2w + MTX | Treatment Arm 1: OKZ 64 mg q4w + MTX | Total |
|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 11.78 | 53.7 years STANDARD_DEVIATION 12.05 | 53.7 years STANDARD_DEVIATION 11.91 |
| Body Mass Index (BMI) | 28.229 kg/m^2 | 28.201 kg/m^2 | 28.215 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 332 Participants | 357 Participants | 689 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 715 Participants | 700 Participants | 1415 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 15 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 46 Participants | 31 Participants | 77 Participants |
| Race/Ethnicity, Customized Other/Mixed | 88 Participants | 97 Participants | 185 Participants |
| Race/Ethnicity, Customized White | 896 Participants | 914 Participants | 1810 Participants |
| Region of Enrollment Argentina | 73 Participants | 81 Participants | 154 Participants |
| Region of Enrollment Belarus | 9 Participants | 9 Participants | 18 Participants |
| Region of Enrollment Brazil | 61 Participants | 55 Participants | 116 Participants |
| Region of Enrollment Bulgaria | 41 Participants | 36 Participants | 77 Participants |
| Region of Enrollment Colombia | 32 Participants | 32 Participants | 64 Participants |
| Region of Enrollment Czechia | 94 Participants | 105 Participants | 199 Participants |
| Region of Enrollment Estonia | 2 Participants | 7 Participants | 9 Participants |
| Region of Enrollment Germany | 20 Participants | 16 Participants | 36 Participants |
| Region of Enrollment Hungary | 36 Participants | 31 Participants | 67 Participants |
| Region of Enrollment Latvia | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Lithuania | 38 Participants | 29 Participants | 67 Participants |
| Region of Enrollment Mexico | 127 Participants | 137 Participants | 264 Participants |
| Region of Enrollment Poland | 133 Participants | 138 Participants | 271 Participants |
| Region of Enrollment Russia | 208 Participants | 217 Participants | 425 Participants |
| Region of Enrollment South Korea | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment Taiwan | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 155 Participants | 150 Participants | 305 Participants |
| Sex: Female, Male Female | 840 Participants | 851 Participants | 1691 Participants |
| Sex: Female, Male Male | 207 Participants | 206 Participants | 413 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 1,043 | 13 / 1,061 |
| other Total, other adverse events | 356 / 1,043 | 386 / 1,061 |
| serious Total, serious adverse events | 129 / 1,043 | 120 / 1,061 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population)
Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term
Time frame: up to Week 126
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Alanine aminotransferase increased | 97 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Neutropenia | 42 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bronchitis | 59 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Metabolism and nutrition disorders | 113 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Aspartate aminotransferase increased | 52 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders | 100 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Upper respiratory tract infection | 59 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications | 101 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders | 149 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders | 88 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations | 284 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders | 60 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders | 125 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders | 60 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Nasopharyngitis | 71 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders | 60 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Leukopenia | 46 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions | 54 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations | 401 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions | 65 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations | 408 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Nasopharyngitis | 87 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Upper respiratory tract infection | 67 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bronchitis | 45 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations | 290 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Alanine aminotransferase increased | 118 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Aspartate aminotransferase increased | 63 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders | 152 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders | 147 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Leukopenia | 60 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Neutropenia | 57 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Metabolism and nutrition disorders | 135 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders | 118 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications | 95 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders | 94 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders | 81 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders | 68 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders | 68 Participants |
Primary
Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)
Time frame: up to Week 126
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Elevation of Blood Lipids | 120 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Infections: Opportunistic Infections | 19 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Malignancies | 9 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Systemic Injection Reactions and Hypersensitivity Reactions | 99 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Systemic Injection Reactions and Hypersensitivity Reactions: Anaphylactic Reactions | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Gastrointestinal Perforations | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Neutropenia, Thrombocytopenia, Leukocytopenia and Pancytopenia | 146 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Potential Hepatotoxicity | 68 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Injection Site Reactions | 34 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Demyelination in Peripheral or Central Nervous System | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Autoimmune Disorders | 48 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Basal cell carcinoma | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Infections | 389 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Autoimmune Disorders | 41 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Infections | 398 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Neutropenia, Thrombocytopenia, Leukocytopenia and Pancytopenia | 168 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Infections: Opportunistic Infections | 22 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Demyelination in Peripheral or Central Nervous System | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Malignancies | 6 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Elevation of Blood Lipids | 138 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Potential Hepatotoxicity | 63 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Systemic Injection Reactions and Hypersensitivity Reactions | 100 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Basal cell carcinoma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Systemic Injection Reactions and Hypersensitivity Reactions: Anaphylactic Reactions | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Injection Site Reactions | 34 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI) | Gastrointestinal Perforations | 2 Participants |
Primary
Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment
Time frame: up to Week 126
Population: Safety Population (3 Subjects discontinued treatment due to an AE but they did not have an AE that led to treatment discontinuation.)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment | 87 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment | 90 Participants |
Primary
Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population)
Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term. Deaths are included.
Time frame: up to Week 126
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Arrhythmia | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Psychiatric disorders | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrial fibrillation | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Invasive ductal breast carcinoma | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Acute coronary syndrome | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Gangrene | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Angina unstable | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Osteomyelitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrioventricular block complete | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Lung adenocarcinoma stage III | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrioventricular block second degree | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Rheumatoid arthritis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Bradycardia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Gastroenteritis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac arrest | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Arthritis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac failure chronic | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: COVID-19 | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac failure congestive | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Influenza | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Coronary artery occlusion | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Bursitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Coronary artery stenosis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Malignant melanoma | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Myocardial infarction | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abdominal wall abscess | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Right ventricular dysfunction | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Intervertebral discitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Sinus tachycardia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Marginal zone lymphoma | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Cervical spinal stenosis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders | 7 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations | 40 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pulmonary embolism | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Meningioma benign | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chronic obstructive pulmonary disease | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Joint abscess | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pulmonary fibrosis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abscess soft tissue | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Respiratory failure | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Stress cardiomyopathy | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Metastatic neoplasm | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Supraventricular tachyarrhythmia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Foot deformity | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Ventricular fibrillation | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Latent tuberculosis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders | 8 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Pancreatic carcinoma metastatic | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Diverticular perforation | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pyelonephritis acute | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Abdominal pain | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Localised infection | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Colitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Salivary gland cancer | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Intervertebral disc protrusion | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Asthmatic crisis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Acute sinusitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastritis erosive | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Joint ankylosis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Abdominal hernia obstructive | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Bronchitis chronic | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Lower respiratory tract infection | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chronic respiratory failure | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Muscle contracture | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chylothorax | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pneumonia | 7 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: effusion | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Ludwig angina | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pleurisy | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Uterine leiomyoma | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pneumothorax | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Musculoskeletal chest pain | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations | 9 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Atypical pneumonia | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Alanine aminotransferase increased | 7 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders | 13 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Hepatic enzyme increased | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Medical device site abscess | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: COVID-19 pneumonia | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Liver function test increased | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Cerebrovascular accident | 4 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders | 6 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Spinal osteoarthritis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Cholelithiasis | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Necrotising fasciitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Cholecystitis chronic | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Dizziness | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Biliary colic | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bartholinitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Hepatotoxicity | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Necrotising soft tissue infection | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Hyperplastic cholecystopathy | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Ischaemic stroke | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Liver injury | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications | 8 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions | 4 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Psychiatric disorders: Completed suicide | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Death | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Syncope | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Sudden death | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Post procedural infection | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Lithiasis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bronchitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Pyrexia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Carotid artery aneurysm | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Sudden cardiac death | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Clavicle fracture | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Vascular stent occlusion | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pulmonary tuberculosis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders | 3 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Encephalopathy | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Uterine polyp | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pyelonephritis | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Endometrial hyperplasia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Renal abscess | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Female genital tract fistula | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Migraine | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Dyspepsia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bullous erysipelas | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastric polyps | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Myelopathy | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastric ulcer | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Salpingo-oophoritis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastrointestinal disorder | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Paraesthesia | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Intestinal obstruction | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Cellulitis | 7 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Obstructive pancreatitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Pineal gland cyst | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Pancreatitis acute | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Scrotal abscess | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Pancreatitis chronic | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Seizure | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Peptic ulcer | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bursitis infective | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Salivary gland calculus | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Subarachnoid haemorrhage | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 11 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Septic shock | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Meningioma | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Transient ischaemic attack | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Benign neoplasm of thyroid gland | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Genital haemorrhage | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Femoral neck fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Intermenstrual bleeding | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Sepsis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Ovarian cyst | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Head injury | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders | 4 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Streptococcal sepsis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Dermatitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Hip fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Skin ulcer | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Cat scratch disease | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Dermatitis contact | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Acetabulum fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Erythema | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Tonsillitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders | 4 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Arthropod bite | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Number of Subjects with at Least One SAE | 129 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Deep vein thrombosis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Comminuted fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Central nervous system neoplasm | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Urinary tract infection | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Cervix carcinoma stage II | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Hypertensive crisis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Concussion | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Peripheral artery occlusion | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Clear cell renal cell carcinoma | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Dengue fever | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Extradural haematoma | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Shock haemorrhagic | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Viral infection | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Colon cancer | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Thrombophlebitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Femur fracture | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abscess limb | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Varicose vein | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Foot fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Endometrial adenocarcinoma | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders | 3 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Viral upper respiratory tract infection | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Humerus fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Calculus urinary | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Device related infection | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Endometrial cancer | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Nephritis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Lower limb fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Wound infection pseudomonas | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Nephrolithiasis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Multiple injuries | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Renal colic | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Erysipelas | 5 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Ureterolithiasis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Muscle rupture | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders | 14 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Febrile neutropenia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Overdose | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Lymphadenopathy | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Device related sepsis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Splenic cyst | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Post procedural complication | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions | 2 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Osteoarthritis | 6 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Abortion spontaneous | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Thoracic vertebral fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Abortion threatened | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Extranodal marginal zone B-cell lymphoma (MALT type) | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Ectopic pregnancy | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Traumatic intracranial haematoma | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Diverticulitis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders: Deafness neurosensory | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Wrist fracture | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders: Vestibular disorder | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Encephalomyelitis | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders | 11 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders: Cataract | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Gastric cancer | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders: Ocular myasthenia | 0 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Acute myocardial infarction | 3 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Immune system disorders | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Osteonecrosis | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Immune system disorders: Hypersensitivity | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Peripheral artery occlusion | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Psychiatric disorders | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Psychiatric disorders: Completed suicide | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Hypertensive crisis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Number of Subjects with at Least One SAE | 120 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations | 47 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pneumonia | 7 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Cellulitis | 4 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Erysipelas | 4 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: COVID-19 | 3 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pyelonephritis acute | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: COVID-19 pneumonia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pyelonephritis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Sepsis | 3 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abscess limb | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Diverticulitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Osteomyelitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abdominal wall abscess | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Abscess soft tissue | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Acute sinusitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Atypical pneumonia | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bartholinitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bronchitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bullous erysipelas | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Bursitis infective | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Cat scratch disease | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Dengue fever | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Device related infection | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Device related sepsis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Encephalomyelitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Gangrene | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Gastroenteritis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Influenza | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Intervertebral discitis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Joint abscess | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Latent tuberculosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Localised infection | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Lower respiratory tract infection | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Ludwig angina | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Medical device site abscess | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Necrotising fasciitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Necrotising soft tissue infection | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Post procedural infection | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Pulmonary tuberculosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Renal abscess | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Salpingo-oophoritis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Scrotal abscess | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Septic shock | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Streptococcal sepsis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Tonsillitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Urinary tract infection | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Viral infection | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Viral upper respiratory tract infection | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Infections and infestations: Wound infection pseudomonas | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders | 11 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Extranodal marginal zone B-cell lymphoma (MALT type) | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Osteoarthritis | 6 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Gastric cancer | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Osteonecrosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Invasive ductal breast carcinoma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Rheumatoid arthritis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Arthritis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Lung adenocarcinoma stage III | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Bursitis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Malignant melanoma | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Marginal zone lymphoma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Cervical spinal stenosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Meningioma benign | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Metastatic neoplasm | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Foot deformity | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Pancreatic carcinoma metastatic | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Intervertebral disc protrusion | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Joint ankylosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Muscle contracture | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Salivary gland cancer | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Uterine leiomyoma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Musculoskeletal chest pain | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders | 6 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Cerebrovascular accident | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Musculoskeletal and connective tissue disorders: Spinal osteoarthritis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Dizziness | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Ischaemic stroke | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications | 14 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Syncope | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Carotid artery aneurysm | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Clavicle fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Encephalopathy | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Migraine | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Myelopathy | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Paraesthesia | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Pineal gland cyst | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Seizure | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Subarachnoid haemorrhage | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Femoral neck fracture | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Head injury | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Hip fracture | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Acetabulum fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Arthropod bite | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Comminuted fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Concussion | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Extradural haematoma | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Femur fracture | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Foot fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Humerus fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Lower limb fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Multiple injuries | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Muscle rupture | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Overdose | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Post procedural complication | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Thoracic vertebral fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Traumatic intracranial haematoma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Injury, poisoning and procedural complications: Wrist fracture | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders | 10 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Acute myocardial infarction | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Arrhythmia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrial fibrillation | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Acute coronary syndrome | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Angina unstable | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrioventricular block complete | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Atrioventricular block second degree | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Bradycardia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac arrest | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac failure chronic | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Cardiac failure congestive | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Coronary artery occlusion | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Coronary artery stenosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Myocardial infarction | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Right ventricular dysfunction | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Sinus tachycardia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Nervous system disorders: Transient ischaemic attack | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders | 12 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pulmonary embolism | 4 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chronic obstructive pulmonary disease | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pulmonary fibrosis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Stress cardiomyopathy | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Supraventricular tachyarrhythmia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Cardiac disorders: Ventricular fibrillation | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders | 12 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Diverticular perforation | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Abdominal pain | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Colitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Respiratory failure | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Asthmatic crisis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastritis erosive | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Bronchitis chronic | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chronic respiratory failure | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Chylothorax | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: effusion | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pleurisy | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Respiratory, thoracic and mediastinal disorders: Pneumothorax | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations | 6 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Alanine aminotransferase increased | 5 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Abdominal hernia obstructive | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Hepatic enzyme increased | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Investigations: Liver function test increased | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders | 3 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Cholelithiasis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Cholecystitis chronic | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Biliary colic | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Hepatotoxicity | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Hyperplastic cholecystopathy | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Hepatobiliary disorders: Liver injury | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions | 4 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Death | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Sudden death | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Lithiasis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Pyrexia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Sudden cardiac death | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | General disorders and administration site conditions: Vascular stent occlusion | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders | 3 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Uterine polyp | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Endometrial hyperplasia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Female genital tract fistula | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Dyspepsia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastric polyps | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastric ulcer | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Gastrointestinal disorder | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Intestinal obstruction | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Obstructive pancreatitis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Pancreatitis acute | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Pancreatitis chronic | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Peptic ulcer | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Gastrointestinal disorders: Salivary gland calculus | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 8 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Meningioma | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Genital haemorrhage | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Intermenstrual bleeding | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Reproductive system and breast disorders: Ovarian cyst | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Dermatitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Skin ulcer | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Dermatitis contact | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Skin and subcutaneous tissue disorders: Erythema | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Benign neoplasm of thyroid gland | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Deep vein thrombosis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Central nervous system neoplasm | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Cervix carcinoma stage II | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Immune system disorders: Hypersensitivity | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Clear cell renal cell carcinoma | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Shock haemorrhagic | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Thrombophlebitis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Colon cancer | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Vascular disorders: Varicose vein | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Endometrial adenocarcinoma | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Calculus urinary | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Neoplasms benign, malignant and unspecified: Endometrial cancer | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Nephritis | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Nephrolithiasis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Renal colic | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Renal and urinary disorders: Ureterolithiasis | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Febrile neutropenia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Lymphadenopathy | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Blood and lymphatic system disorders: Splenic cyst | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Abortion spontaneous | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Abortion threatened | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Pregnancy, puerperium and perinatal conditions: Ectopic pregnancy | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders: Deafness neurosensory | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Ear and labyrinth disorders: Vestibular disorder | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders | 2 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders: Cataract | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Eye disorders: Ocular myasthenia | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population) | Immune system disorders | 0 Participants |
Primary
Incidence Rate of Treatment Emergent AESIs (Safety Population)
Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Time frame: up to Week 126
Population: An AE is defined as treatment-emergent under a given study treatment, if AE's onset date is on or after the date of first dose the corresponding treatment and prior to initiation of the next study treatment, if any.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence Rate of Treatment Emergent AESIs (Safety Population) | 40.49 subjects per 100 subject-years |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence Rate of Treatment Emergent AESIs (Safety Population) | 42.13 subjects per 100 subject-years |
Primary
Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure
Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Time frame: up to Week 126
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure | 48.75 subjects per 100 subject-years |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure | 49.84 subjects per 100 subject-years |
Primary
Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure
Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Time frame: up to Week 126
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure | 7.74 subjects per 100 subject-years |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure | 7.37 subjects per 100 subject-years |
Secondary
American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR20 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥20% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)
Time frame: up to Week 82
Population: mITT Population Intermediate missing data are imputed using surrounding visits. Response is calculated relative to the core baseline, the last available assessment prior to the first dose of the study treatment in the core study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 839 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 780 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 850 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 777 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 795 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 811 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 861 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 830 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 863 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 851 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 829 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 795 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 783 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 774 Participants |
Secondary
American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR50 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82 American College of Rheumatology 50 % response is a composite defined as a ≥ 50% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 50% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)
Time frame: up to Week 82
Population: mITT Population Intermediate missing data are imputed using surrounding visits. Response is calculated relative to the core baseline, the last available assessment prior to the first dose of the study treatment in the core study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 597 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 563 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 607 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 584 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 600 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 608 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 598 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 619 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 601 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 607 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 610 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 594 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 606 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 583 Participants |
Secondary
American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR70 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82 American College of Rheumatology 70 % response is a composite defined as a ≥ 70% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 70% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)
Time frame: up to Week 82
Population: mITT Population Intermediate missing data are imputed using surrounding visits. Response is calculated relative to the core baseline, the last available assessment prior to the first dose of the study treatment in the core study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 367 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 370 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 358 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 373 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 375 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 382 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 330 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 82 OLE | 393 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 12 OLE | 362 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 20 OLE | 353 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 28 OLE | 357 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 40 OLE | 369 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 52 OLE | 387 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82 | Week 64 OLE | 387 Participants |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 12
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Week 12 OLE | 1.03 score on a scale | Standard Deviation 0.632 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Change from Core Baseline | -0.67 score on a scale | Standard Deviation 0.628 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Week 12 OLE | 1.00 score on a scale | Standard Deviation 0.628 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12 | Change from Core Baseline | -0.74 score on a scale | Standard Deviation 0.648 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 20
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Week 20 OLE | 1.00 score on a scale | Standard Deviation 0.647 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Change from Core Baseline | -0.70 score on a scale | Standard Deviation 0.631 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Week 20 OLE | 0.99 score on a scale | Standard Deviation 0.621 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20 | Change from Core Baseline | -0.74 score on a scale | Standard Deviation 0.64 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 28
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Week 28 OLE | 0.99 score on a scale | Standard Deviation 0.632 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Change from Core Baseline | -0.71 score on a scale | Standard Deviation 0.645 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Week 28 OLE | 0.99 score on a scale | Standard Deviation 0.627 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28 | Change from Core Baseline | -0.75 score on a scale | Standard Deviation 0.652 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 40
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Change from Core Baseline | -0.72 score on a scale | Standard Deviation 0.663 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Week 40 OLE | 0.97 score on a scale | Standard Deviation 0.651 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Week 40 OLE | 0.99 score on a scale | Standard Deviation 0.635 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Change from Core Baseline | -0.75 score on a scale | Standard Deviation 0.672 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 52
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Week 52 OLE | 0.97 score on a scale | Standard Deviation 0.653 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Change from Core Baseline | -0.72 score on a scale | Standard Deviation 0.67 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Week 52 OLE | 0.96 score on a scale | Standard Deviation 0.623 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52 | Change from Core Baseline | -0.77 score on a scale | Standard Deviation 0.671 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 64
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Week 64 OLE | 0.95 score on a scale | Standard Deviation 0.641 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Change from Core Baseline | -0.74 score on a scale | Standard Deviation 0.643 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Week 64 OLE | 0.97 score on a scale | Standard Deviation 0.635 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64 | Change from Core Baseline | -0.77 score on a scale | Standard Deviation 0.671 |
Secondary
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: Core baseline, Week 82
Population: mITT Population Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Core Baseline | 1.70 score on a scale | Standard Deviation 0.581 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Change from Core Baseline | -0.72 score on a scale | Standard Deviation 0.68 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Week 82 OLE | 0.97 score on a scale | Standard Deviation 0.667 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Core Baseline | 1.74 score on a scale | Standard Deviation 0.561 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Week 82 OLE | 0.98 score on a scale | Standard Deviation 0.667 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82 | Change from Core Baseline | -0.74 score on a scale | Standard Deviation 0.695 |
Secondary
Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI)
CDAI Range: 0 (the best outcome) - 76 (the worst outcome), with a decrease from baseline indicating improvement. The CDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: CDAI = SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS)
Time frame: up to week 82
Population: Subjects with a missing baseline are not included. Intermediate missing data are imputed using surrounding visits. Baseline is defined as the last available assessment prior to the first dose of the study treatment in the core study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 20 | -29.87 index units | Standard Deviation 12.553 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 40 | -30.88 index units | Standard Deviation 11.992 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 12 OLE Actual Values | 10.92 index units | Standard Deviation 9.349 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 52 OLE Actual Values | 8.69 index units | Standard Deviation 7.954 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 28 OLE Actual Values | 9.77 index units | Standard Deviation 8.583 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 52 | -31.35 index units | Standard Deviation 11.855 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 20 OLE Actual Values | 10.30 index units | Standard Deviation 9.489 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 64 OLE Actual Values | 8.42 index units | Standard Deviation 7.997 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 28 | -30.35 index units | Standard Deviation 12.111 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 64 | -31.68 index units | Standard Deviation 11.896 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 12 | -29.35 index units | Standard Deviation 12.093 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 82 OLE Actual Values | 9.66 index units | Standard Deviation 10.513 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 40 OLE Actual Values | 9.19 index units | Standard Deviation 8.498 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 82 | -30.48 index units | Standard Deviation 12.878 |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Core Baseline Actual Values | 40.20 index units | Standard Deviation 11.252 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 82 | -30.58 index units | Standard Deviation 14.404 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Core Baseline Actual Values | 40.06 index units | Standard Deviation 11.605 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 12 OLE Actual Values | 10.54 index units | Standard Deviation 9.106 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 12 | -29.54 index units | Standard Deviation 12.946 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 20 OLE Actual Values | 9.90 index units | Standard Deviation 8.755 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 20 | -30.23 index units | Standard Deviation 12.821 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 28 OLE Actual Values | 9.85 index units | Standard Deviation 8.696 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 28 | -30.36 index units | Standard Deviation 12.849 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 40 OLE Actual Values | 9.34 index units | Standard Deviation 8.235 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 40 | -30.80 index units | Standard Deviation 13.025 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 52 OLE Actual Values | 8.61 index units | Standard Deviation 7.776 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 52 | -31.60 index units | Standard Deviation 12.639 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 64 OLE Actual Values | 8.36 index units | Standard Deviation 7.798 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Change from Core Baseline at week 64 | -31.85 index units | Standard Deviation 12.484 |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI) | Week 82 OLE Actual Values | 9.36 index units | Standard Deviation 10.236 |
Secondary
Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82
Number and Proportion of subjects with DAS28 low disease activity (based on DAS28 C-reactive protein (CRP) \< 3.2), who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82. The DAS28 (CRP) was calculated in the statistical database for analysis purposes using the Swollen joint count (SJC) (28 joints), Tender joint count (TJC) (28 joints), CRP level, and the Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) (100 mm VAS, where 0 is no disease activity and 100 was maximal disease activity) according to the following formula: \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.36 × natural log (CRP+1)\] + \[0.014 × VAS\] + 0.96.
Time frame: up to Week 82
Population: Intermediate missing data are imputed using surrounding visits. The Core Baseline value was defined as the baseline value from the core study for subjects that enrol into the OLE study.The OLE Baseline value was defined as the last available measurement prior to the first OLE dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 82 OLE | 706 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 12 OLE | 681 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Core Baseline | 1 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 20 OLE | 703 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 52 OLE | 679 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 28 OLE | 684 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | OLE Baseline | 573 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 40 OLE | 688 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 64 OLE | 681 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 82 OLE | 712 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 40 OLE | 691 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 52 OLE | 680 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 64 OLE | 678 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Core Baseline | 1 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | OLE Baseline | 537 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 12 OLE | 685 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 20 OLE | 714 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82 | Week 28 OLE | 694 Participants |
Secondary
Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82
The number and proportion of subjects with HAQ-DI improvement ≥ 0.22 Against OLE Baseline. HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3, where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Time frame: up to week 82
Population: Intermediate missing data are imputed using surrounding visits. The OLE Baseline value was defined as the last available measurement prior to the first OLE dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 28 OLE | 326 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 52 OLE | 322 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 20 OLE | 319 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 64 OLE | 317 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 40 OLE | 310 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 82 OLE | 326 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 12 OLE | 297 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 82 OLE | 373 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 12 OLE | 324 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 20 OLE | 341 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 28 OLE | 320 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 40 OLE | 333 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 52 OLE | 338 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82 | Week 64 OLE | 326 Participants |
Secondary
Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82
The number and proportion of subjects with SDAI score ≤ 3.3 (considered to be in remission). The SDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), CRP (mg/dL), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS) + CRP (mg/dL)
Time frame: up to week 82
Population: Intermediate missing data are imputed using surrounding visits. The Core Baseline value was defined as the baseline value from the core study for subjects that enrol into the OLE study.The OLE Baseline value was defined as the last available measurement prior to the first OLE dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | OLE Baseline | 137 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 40 OLE | 204 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 20 OLE | 192 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 52 OLE | 218 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 12 OLE | 161 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 64 OLE | 223 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 28 OLE | 196 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 82 OLE | 231 Participants |
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Core Baseline | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 82 OLE | 267 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Core Baseline | 0 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | OLE Baseline | 145 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 12 OLE | 190 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 20 OLE | 197 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 28 OLE | 196 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 40 OLE | 211 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 52 OLE | 225 Participants |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82 | Week 64 OLE | 257 Participants |