Rheumatoid Arthritis
Conditions
Keywords
an inadequate response to anti -TNF therapy
Brief summary
A randomised, double blind, parallel group, multicentre study yo compare the pharmacokinetics, pharmacokinetics, safety and efficacy of SAIT101 versus MabThera® versus Rituxan® in patients with rheumatoid arthritis.
Detailed description
This is a randomized, double-blind, parallel group, multicenter study to compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, efficacy, tolerability, and immunogenicity of SAIT101 (biosimilar rituximab) versus MabThera® versus Rituxan® in patients with rheumatoid arthritis (RA). This study will take place globally across approximately 75 study centers in order to randomize approximately 282 patients. The study consists of Part A from baseline for PK and efficacy analysis, followed by Part B from Week 24 to 52 for safety follow-up in which collects transition data.
Interventions
BIOLOGICALSAIT101
1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible patients.
BIOLOGICALMabThera
1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible patients.
BIOLOGICALRituxan
1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible patients.
Sponsors
Archigen Biotech Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
In Part A, patients are randomized in a 1:1:1 ratio to receive one course (baseline and Week 2) of SAIT101 (n=94) versus Rituxan® (n=94) versus MabThera® (n=94). At Week 24, patients are evaluated for the second course (Week 24 and 26) of the infusion. In Part B, eligible patients in the SAIT101 arm receive the second course of SAIT101 treatment. Eligible patients in the MabThera® arm receive the second course of MabThera® treatment. Eligible patients in the Rituxan® arm are randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment. Patients are followed up for safety until Week 52.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1\. Severe RA defined as: * Diagnosis of RA according to the revised (1987) American College of Rheumatology (ACR) criteria for the classification of RA for at least 3 months prior to screening visit (see Appendix 3). * And ≥6 swollen joints and ≥6 tender/painful joints (from the 66/68 joint count system). * And C-reactive protein (CRP) ≥1.0 mg/dL or an erythrocyte sedimentation rate (ESR) ≥28 mm/hour at Screening. * And positive rheumatoid factor (RF) (≥20 units/mL) or anti cyclic citrullinase peptide (CCP) antibodies (≥10 units/mL) at Screening. 2\. Patients with severe RA who have had an inadequate response to at least 3 months' treatment (according to the approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of intolerable AE or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe toxicity) to anti-tumour necrosis factor (TNF) therapy (experience of severe adverse event (AE) or toxicity). 3\. Current treatment for RA on an outpatient basis: * Receiving methotrexate (MTX) 7.5 - 25mg/week (oral or parenteral) for at least 12 weeks, including the last 4 weeks prior to Day 1 at a stable dose, via the same route of administration, dose, and formulation. Patients receiving a lower dose of MTX (\<10 mg/week), stable for 4 weeks prior to Day 1, should be doing so as a result of a documented evidence of intolerance to higher doses of MTX.
Exclusion criteria
1. Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug. 2. Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 1991 Revised Criteria) (see Appendix 4) or wheelchair/bed bound. 3. History of or current inflammatory joint disease other than RA (including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease). 4. History of or current systemic autoimmune disorder (including but not limited to systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, Felty syndrome, scleroderma, inflammatory myopathy, fibromyalgia, juvenile idiopathic arthritis, mixed connective tissue disease, vasculitis or other overlap syndrome), with the exception of the secondary Sjögren's syndrome. 5. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening. 6. History of opportunistic infection. 7. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) and infected prosthetic joint. 8. Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. anti infective agents within 4 weeks prior to Screening or oral anti-infective agents within 2 weeks prior to Screening or use of antibiotic therapy three or more times in the last six months prior to Screening 9. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology. * Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level \<20 IU/mL (or 112 copies/mL) by polymerase chain reaction (PCR). These HBV patients must be willing to undergo monthly PCR HBV DNA testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An HBV re-test will be performed monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36, 52, and unscheduled visit if required. * Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+ and anti HBc-). * Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV ribonucleic acid (RNA). 10. Confirmed current active tuberculosis (TB). • Patients with latent TB as determined by positive QuantiFERON-TB test may be enrolled if such patients have written confirmation from health care provider (e.g., Pulmonologist or Infection Specialist) of adequate prophylaxis before or within the screening period and no evidence of tuberculosis on a chest X-ray performed within 3 months from Day 1. • Screening period can be extended to 60 days for prophylaxis of latent TB. • QuantiFERON-TB test can be re-tested, if inconclusive. 11. Any significant cardiac disease (e.g., coronary artery disease with unstable angina, coronary heart failure New York Heart Association Class III and IV, familial long QT syndrome, uncontrolled cardiac disease). 12. History of moderate to severe chronic obstructive pulmonary disease (COPD) and/or history of severe COPD exacerbation(s) within the last 12 months of Screening. 13. Vaccination with live or attenuated vaccines within 6 weeks prior to first dose of study drug or planned administration during study participation or within 4 weeks following last dose of study drug. Treatment with IV Gamma Globulin or the Prosorba® Column within 6 months prior to Day 1. 14. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product. 15. Hypogammaglobulinemia at screening (Immunoglobulin G (IgG) \<600 mg/dL). 16. Patients with hemoglobin \<8.5 g/dL, absolute neutrophil count (ANC) \<1,500 cells/µL or platelet count \<75,000 cells/µL at Screening. If a patient has findings marginally below this limit, re testing is allowed, at the Investigator's discretion, within the 30 day period between Visit 1 and Visit 2. • Creatinine clearance \< 50 mL/min (Cockcroft-Gault formula) • Liver function: Total bilirubin \>2.0 mg/dL (\>34 µmol/L) except for patients with Gilbert's Syndrome or hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN). Patients with total bilirubin \>2.0 mg/dL possibly due to Gilbert's Syndrome should have a direct bilirubin checked. If the direct bilirubin is normal and medical history is suggestive/positive for Gilbert's Syndrome, the patient successfully meets the criteria. The AST and ALT may be repeated once within the Screening period if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion. 18\. History of cancer within the last 5 years prior to Screening, treated with anti-cancer chemotherapy, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured). 19\. Major surgical procedure within 4 weeks prior to or planned within 24 weeks of Day 1, with the exception of surgical procedures for dental prosthesis. 20\. Previous treatment with a B cell modulating or B cell depletion therapy, such as, but not limited to rituximab, belimumab, atacicept, tabalumab, ocrelizumab, ofatumumab, obinutuzumab, epratuzumab and other experimental treatments. 21\. Injectable corticosteroids within 6 weeks prior to Day 1. 22\. Participation in a previous clinical study within 4 weeks of Screening or having received treatment with a drug that has not received regulatory approval for any indication within a minimum of 5 half-lives prior to Day 1. 23\. Patients who, based on the Investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may also include cardiovascular, vascular, pulmonary, hepatic, renal, endocrine or neurological conditions as determined by medical history, physical examination, laboratory tests or electrocardiogram (ECG). 24\. Patients who, in the judgment of the Investigator, are likely to be non-compliant or uncooperative during the study. 25\. History of substance abuse (alcohol or drug). 26\. History of demyelinating disorders (such as multiple sclerosis or Guillain-Barré syndrome). 27\. Patients at risk of progressive multifocal leukoencephalopathy (PML): * Patients with immune deficiency such as transplant patients on immunosuppressive medications * Patients receiving certain kinds of chemotherapy * Patients receiving natalizumab (Tysabri®) for multiple sclerosis * Patients with psoriasis on longer term efalizumab (Raptiva®) or patients with acquired immunodeficiency syndrome (AIDS)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC0-∞) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Area Under the Plasma Concentration from time 0 to infinity (AUC0-∞ (infinity). Calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the elimination rate constant: AUC(0-last) + C(last)/λz. |
| Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t). Geometric means by treatment (Pharmacokinetic Analysis Set). |
| Change From Baseline in DAS28-CRP at Week 24 | Baseline and Week 24 | Disease Activity Score 28 C-reactive protein score (DAS28-CRP) at Week 24 (Full Analysis Set). CRP samples were collected at Baseline and Weeks 8, 16 and 24. DAS28-CRP was calculated using the following equation: \[0.56\*Square Root (SQRT) (tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.36\*ln(CRP+1)\]\*1.10+1.15. Total DAS28-CRP scores were calculates and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and \<2.6. Low disease activity corresponds to 2.6 to \<3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1. |
| Trough Concentration (Ctrough) Before the Second Infusion on Day 15 | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Trough concentration (Ctrough) before the second infusion on Day 15 (Dose 2). Trough (pre-dose) concentration prior to second infusion on Day 15 obtained directly from the observed concentration versus time data. |
| Peak Plasma Concentration (Cmax) After Day 15 Infusion | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Maximum Plasma Concentration (Cmax) after Day 15 infusion (Dose 2) |
| Area Under the Plasma Concentration Versus Time Curve (AUC0-D15) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Area Under the Concentration verses time from time 0 to Day 15 prior to infusion (AUC0-D15) calculated by linear up/log down trapezoidal summation. Actual time/concentration on Day 15 was used for the calculation of this parameter unless the parameter was derived by interpolation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Clearance (CL) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Systemic clearance (CL) over the first dosing period calculated as dose (first + second dose) divided by AUC(0-∞). |
| Volume of Distribution (VD) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Volume of distribution (VD) over the first dosing period calculated as dose (first + second dose) divided by \[λz AUC(0-∞)\] |
| Terminal Half-life (T1/2) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Terminal half-life determined as ln2/λz. |
| Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) samples taken at Baseline and Weeks 8, 16, 24, 36 and 52. DAS28-CRP was calculated using the following equation: \[0.56\*Square Root (SQRT) (tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.36\*ln(CRP+1)\]\*1.10+1.15. Total DAS28-CRP scores are presented and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and \<2.6. Low disease activity corresponds to 2.6 to \<3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1. |
| American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | American Collage of Rheumatology (ACR) 20% response criteria (ACR20) response rates were assessed at Baseline and Weeks 8, 16, 24, 36 and 52. An ACR20 response is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). |
| American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: American Collage of Rheumatology 50% response criteria (ACR50) response rates and American Collage of Rheumatology 70% response criteria (ACR70) at weeks 8, 16, 24, 36 and 52. An ACR50 response is defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). An ACR70 response is defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). |
| Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Area under the concentration time curve week 2 to week 24 (AUC(w2-24) calculated by linear up/log down trapezoidal summation. |
| Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12)) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8 and 12. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Area under the concentration time curve Day 0 to Week 12 calculated by linear up/log down trapezoidal summation. |
| Time to Maximum Plasma Concentration (Tmax) (Dose 1) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Maximum plasma concentration over the first dosing interval obtained directly from the observed concentration versus time data. |
| Time to Maximum Plasma Concentration (Tmax) (Dose 2) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Time of maximum concentration postinfusion over the second dosing interval, obtained directly from the observed concentration versus time data. |
| Apparent Terminal Rate Constant (λz) | Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacokinetic endpoint: Apparent terminal rate constant (λz) determined by linear regression of the terminal points of the log-linear concentration-time curve. Best fit method followed by visual assessment was used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points was used for determination. |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | the Health Assessment Questionnaire-Disability Index (HAQ-DI) contains 20 questions split into 8 categories (dressing & grooming, arising, eating, walking, hygiene, reach, grip & activities). Scores were: 0 = Without ANY Difficulty; 1 = With SOME Difficulty; 2 = With MUCH Difficulty; 3 = UNABLE to Do. Total scores were calculated as the summed category scores divided by the number of categories. Total HAQ-DI scores are presented which range from 0 to 3. Higher scores represent a worse outcome. Scores of 0 to 1 represent mild to moderate difficulty, 1 to 2 moderate disability, and 2 to 3 severe to very severe disability. |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | C-reactive protein (CRP) level (Mg/L). CRP is a marker for inflammation. a normal reading is \<3 Mg/L. Higher values indicate disease related inflammation and increased cardiovascular risk. CRP levels between 3 Mg/L and 10 Mg/L are mildly elevated. Levels between 10 Mg/L and 100 Mg/L are moderately elevated and CRP levels above 100 Mg/L are severely elevated. |
| Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Disease Activity Score 28- Erythrocyte Sedimentation Rate (DAS28-ESR) consisted of tender joint counts (TJC), swollen joint counts (SJC) & erythrocyte sedimentation rate (ESR). The formula is: \[0.56\*SQRT(tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.7\*ln(ESR)\]+0.014\*patient global health assessment. Total DAS28-ESR scores are presented. Total scores range from 2 (minimum) to 10 (maximum). A lower score represents a better patient outcome. A DAS28-ESR of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission. |
| Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: number of participants with a major clinical response defined as a continuous ACR70 from Baseline (Day 1) for at least 24 weeks. ACR70 is a measure based on American College of Rheumatology criteria of at least a 70% improvement in the number of tender and swollen joints, and a 70% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels. |
| Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Number if Participants with a Clinical Remission Response (CRR) defined by the Simplified Disease Activity Index (SDAI) \<3.3 at weeks 8, 16, 24, 36 and 52 (EOS). |
| Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: Proportion of participants with European League Against Rheumatism (EULAR) response (defined as good response, moderate response or no response) at weeks 8, 16, 24 36 and 52 (EOS). EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The DAS28-CRP was classified into 3 categories: low disease activity (\<= 3.2), moderate disease activity (\> 3.2 and \<= 5.1) and high disease activity (\> 5.1). Good response was defined as \>1.2 improvement in the DAS28-CRP from baseline with low disease activity. |
| Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | Baseline (Day 1) and Weeks 8, 16, 24, 36 and 52 (EOS) | Change from baseline (Day 1) in immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) levels (mg/dL) at Week 8, 16, 24 36 and 52 (End of study) |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: Individual components of the ACR improvement criteria on Day 1 and at weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and tender joint count (TJC) (the 66/68 joint count system). SJC and TJC assess the level of skeletal disease involvement. The 66/68 Joint Count evaluates 66 joints for swelling and 68 joints for tenderness. |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians global assessment of disease activity (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]). Where 0 = no disease activity and 100 = maximum disease activity. |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]). Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]) where 0 = no pain and 100 = severe pain. |
| Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Baseline and Weeks 8, 16, 24, 36 and 52 (EOS) | Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants global assessment of disease activity (assessed on 1 to 100 mm visual analogue scale \[VAS\]). Patients rate how their Rheumatoid Arthritis has affected them, where 0 = very well and 100 = very poor. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24 | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacodynamic endpoint: proportion of participants (n) with depletion of CD19+ B-cell count up to week 24 (Pharmacodynamic analysis set). |
| Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator. | Pharmacodynamic endpoint: Descriptive statistics (mean \[SD\]) of the change from baseline in CD19+ B-cell count during the study period (Day 15 \[AUEC(0-d15\] and Week 24 \[AUEC(0-w24\]) |
| Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator. | Area under the concentration time curve of CD19 B-cell count change at Day 15 (AUEC0-d15) and week 24 (AUEC0-w24) based on change from baseline and percent of baseline values |
| Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator. | Number of participants with CD19+ B-cell count recover versus baseline. Incidence of B-Cell recovery was defined as either CD19+ B-cell counts retuned to baseline or the lower limit or normal of 110 cells/µL at week 24). |
| Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator. | Duration of CD19+ B-cell depletion (only participants that returned to non-depletion at or before week 24 were included) |
| Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion | Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator. | Time needed to CD19+ B-cell depletion in Part A (calculated as the first time CD19+ B-cell count below 20/µL minus time of first dosing in days). |
| Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | Baseline (Day 1) and Weeks 8, 16, 24, 26 & 52 (EOS) | Pharmacodynamic endpoint: Change from baseline (Day 1) in C-reactive protein (CRP) levels (mg/dL) at weeks 8, 16, 24, 36 and 52 (EOS) |
Countries
Bosnia and Herzegovina, Bulgaria, Czechia, Germany, Hungary, India, Mexico, Poland, South Korea, Spain, United States
Participant flow
Recruitment details
This was a global study conducted in 66 study centres. The first participant entered the study on 11 October 2016 and the date of the last participants last study visit was 07 November 2018.
Participants by arm
| Arm | Count |
|---|---|
| SAIT101 SAIT101: 1,000 mg i.v. of SAIT101 on Day 1 and 15. 1,000 mg i.v. of SAIT101 on week 24 and 26 for eligible participants. | 98 |
| MabThera MabThera: 1,000 mg i.v. of MabThera® on Day 1 and 15. 1,000 mg i.v. of MabThera® on week 24 and 26 for eligible participants. | 98 |
| Rituxan Rituxan: 1,000 mg i.v. of Rituxan® on Day 1 and 15. 1,000 mg i.v. of Rituxan® on week 24 and 26 for eligible participants. | 98 |
| Total | 294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part A (All Participants) | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Part A (All Participants) | Protocol non-compliance | 3 | 4 | 5 | 0 |
| Part A (All Participants) | Withdrawal by Subject | 3 | 5 | 6 | 0 |
| Part B (All Participants) | Lost to Follow-up | 1 | 1 | 2 | 2 |
| Part B (All Participants) | Protocol non-compliance | 0 | 0 | 1 | 0 |
| Part B (All Participants) | Withdrawal by Subject | 2 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Rituxan | SAIT101 | MabThera |
|---|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 11.79 | 52.1 years STANDARD_DEVIATION 12.09 | 50.9 years STANDARD_DEVIATION 12.41 | 52.5 years STANDARD_DEVIATION 10.87 |
| Age, Customized 18-60 years | 222 Participants | 71 Participants | 76 Participants | 75 Participants |
| Age, Customized >60 years | 72 Participants | 27 Participants | 22 Participants | 23 Participants |
| Anti-drug Antibody (ADA) Status Positive | 7 Participants | 4 Participants | 2 Participants | 1 Participants |
| Body Mass Index (BMI) | 27.2 Kg/m^2 STANDARD_DEVIATION 5.63 | 26.7 Kg/m^2 STANDARD_DEVIATION 5.95 | 27.5 Kg/m^2 STANDARD_DEVIATION 5.48 | 27.5 Kg/m^2 STANDARD_DEVIATION 5.46 |
| C-reactive protein | 17.0 mg/L STANDARD_DEVIATION 2.99 | 16.2 mg/L STANDARD_DEVIATION 17.91 | 19.5 mg/L STANDARD_DEVIATION 28.99 | 15.3 mg/L STANDARD_DEVIATION 20.63 |
| Disease activity score based on a 28-joint count-C-Reactive Protein (DAS-28-CRP( | 5.25 units on a scale STANDARD_DEVIATION 0.843 | 5.17 units on a scale STANDARD_DEVIATION 833 | 5.28 units on a scale STANDARD_DEVIATION 0.89 | 5.29 units on a scale STANDARD_DEVIATION 0.807 |
| Disease activity score based on a 28-joint count - Erythrocyte sedimentation Rate (DAS28-ESR) | 6.52 units on a scale STANDARD_DEVIATION 0.793 | 6.48 units on a scale STANDARD_DEVIATION 0.758 | 6.54 units on a scale STANDARD_DEVIATION 0.844 | 6.53 units on a scale STANDARD_DEVIATION 0.781 |
| Disease duration | 10.1 years STANDARD_DEVIATION 7.22 | 9.3 years STANDARD_DEVIATION 7.1 | 9.8 years STANDARD_DEVIATION 6.73 | 11.2 years STANDARD_DEVIATION 7.72 |
| Erythrocyte sedimentation rate | 50.0 mm/hr STANDARD_DEVIATION 24.31 | 51.5 mm/hr STANDARD_DEVIATION 23.35 | 51.0 mm/hr STANDARD_DEVIATION 26.58 | 47.5 mm/hr STANDARD_DEVIATION 22.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 89 Participants | 29 Participants | 30 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 205 Participants | 69 Participants | 68 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Health Assessment Questionnaire Disability Index (HAQ-DI) Score | 1.7 Score STANDARD_DEVIATION 0.62 | 1.6 Score STANDARD_DEVIATION 0.64 | 1.7 Score STANDARD_DEVIATION 0.57 | 1.7 Score STANDARD_DEVIATION 0.64 |
| Height | 162.4 cm STANDARD_DEVIATION 8.83 | 163.3 cm STANDARD_DEVIATION 8.37 | 162.6 cm STANDARD_DEVIATION 9.29 | 161.3 cm STANDARD_DEVIATION 8.79 |
| Patient Global Assessments Visual Analogue Scale (VAS) Score | 69.1 units on a scale STANDARD_DEVIATION 16.82 | 70.8 units on a scale STANDARD_DEVIATION 17.04 | 68.9 units on a scale STANDARD_DEVIATION 15.87 | 67.6 units on a scale STANDARD_DEVIATION 17.53 |
| Patient Pain Assessment VAS Score | 68.8 units on a scale STANDARD_DEVIATION 19.27 | 70.7 units on a scale STANDARD_DEVIATION 19.06 | 67.0 units on a scale STANDARD_DEVIATION 18.71 | 68.8 units on a scale STANDARD_DEVIATION 20.02 |
| Physician Global Assessment VAS Score | 70.1 units on a scale STANDARD_DEVIATION 14.51 | 69.8 units on a scale STANDARD_DEVIATION 14.32 | 71.0 units on a scale STANDARD_DEVIATION 14.3 | 69.4 units on a scale STANDARD_DEVIATION 15.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 65 Participants | 21 Participants | 24 Participants | 20 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 24 Participants | 18 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 160 Participants | 52 Participants | 52 Participants | 56 Participants |
| Region of Enrollment Bosnia and Herzegovina | 7 participants | 1 participants | 4 participants | 3 participants |
| Region of Enrollment Bulgaria | 13 participants | 4 participants | 4 participants | 5 participants |
| Region of Enrollment Czechia | 12 participants | 2 participants | 7 participants | 3 participants |
| Region of Enrollment Germany | 8 participants | 2 participants | 2 participants | 3 participants |
| Region of Enrollment Hungary | 7 participants | 4 participants | 3 participants | 0 participants |
| Region of Enrollment India | 46 participants | 17 participants | 13 participants | 16 participants |
| Region of Enrollment Mexico | 69 participants | 21 participants | 27 participants | 21 participants |
| Region of Enrollment Poland | 57 participants | 23 participants | 15 participants | 19 participants |
| Region of Enrollment South Korea | 14 participants | 6 participants | 5 participants | 3 participants |
| Region of Enrollment Spain | 33 participants | 12 participants | 9 participants | 12 participants |
| Region of Enrollment United States | 28 participants | 6 participants | 9 participants | 13 participants |
| Sex: Female, Male Female | 240 Participants | 80 Participants | 79 Participants | 81 Participants |
| Sex: Female, Male Male | 54 Participants | 18 Participants | 19 Participants | 17 Participants |
| Swollen Joint Count (SJC66) | 14.5 Joints STANDARD_DEVIATION 7.14 | 13.0 Joints STANDARD_DEVIATION 6.19 | 15.2 Joints STANDARD_DEVIATION 7.97 | 15.2 Joints STANDARD_DEVIATION 7.01 |
| Tender Joint Count (TJC68) | 21.4 Joints STANDARD_DEVIATION 11.93 | 20.0 Joints STANDARD_DEVIATION 10.84 | 21.7 Joints STANDARD_DEVIATION 11.08 | 22.6 Joints STANDARD_DEVIATION 13.66 |
| Weight | 72.2 kg STANDARD_DEVIATION 17.47 | 71.6 kg STANDARD_DEVIATION 17.99 | 73.0 kg STANDARD_DEVIATION 17.62 | 71.9 kg STANDARD_DEVIATION 16.94 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 98 | 1 / 98 |
| other Total, other adverse events | 39 / 98 | 37 / 98 | 43 / 98 |
| serious Total, serious adverse events | 7 / 98 | 7 / 98 | 13 / 98 |
Outcome results
Primary
Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t)
Pharmacokinetic endpoint: Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t). Geometric means by treatment (Pharmacokinetic Analysis Set).
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. (AUC(0-t) could not be determined for 15 participants in the SAIT101 arm, 23 participants in the MabThera arm and 17 in the Rituxan arm as the Week 24 sample was either collected post-dose (i.e. not evaluable), was out of the collection window or was missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t) | 144500 h*µg/mL | Geometric Coefficient of Variation 34.2 |
| MabThera | Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t) | 151600 h*µg/mL | Geometric Coefficient of Variation 33.2 |
| Rituxan | Area Under the Concentration Time Cure From Time 0 to Last Quantifiable Concentration (AUC0-t) | 154600 h*µg/mL | Geometric Coefficient of Variation 35.6 |
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model (ANOVA) with fixed effect for treatment90% CI: [87.07, 104.37]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [85.54, 102.15]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model (ANOVA) with fixed effect for treatment90% CI: [89.49, 107.45]
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC0-∞)
Pharmacokinetic endpoint: Area Under the Plasma Concentration from time 0 to infinity (AUC0-∞ (infinity). Calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the elimination rate constant: AUC(0-last) + C(last)/λz.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. AUC0-∞ could not be calculated for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined, the samples were missing or the Regulatory Scientific Quality (RSQ) was \<0.800.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Area Under the Plasma Concentration Versus Time Curve (AUC0-∞) | 152300 h*µg/mL | Geometric Coefficient of Variation 34.6 |
| MabThera | Area Under the Plasma Concentration Versus Time Curve (AUC0-∞) | 161900 h*µg/mL | Geometric Coefficient of Variation 32.2 |
| Rituxan | Area Under the Plasma Concentration Versus Time Curve (AUC0-∞) | 161300 h*µg/mL | Geometric Coefficient of Variation 33.3 |
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [86.91, 101.81]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [87.21, 102.16]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [92.68, 108.65]
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC0-D15)
Pharmacokinetic endpoint: Area Under the Concentration verses time from time 0 to Day 15 prior to infusion (AUC0-D15) calculated by linear up/log down trapezoidal summation. Actual time/concentration on Day 15 was used for the calculation of this parameter unless the parameter was derived by interpolation.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. AUC0-D15 could not be determined for 3 participants in the SAIT101 arm, 5 participants in the MabThera arm and 10 participants in the Rituxan arm as either the 336-hours blood sample was collected \<312 hours or samples were missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Area Under the Plasma Concentration Versus Time Curve (AUC0-D15) | 42950 h*µg/mL | Geometric Coefficient of Variation 26.7 |
| MabThera | Area Under the Plasma Concentration Versus Time Curve (AUC0-D15) | 44600 h*µg/mL | Geometric Coefficient of Variation 25.6 |
| Rituxan | Area Under the Plasma Concentration Versus Time Curve (AUC0-D15) | 43540 h*µg/mL | Geometric Coefficient of Variation 24.1 |
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [90.52, 102.46]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [92.64, 105.05]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [96.14, 109.14]
Primary
Change From Baseline in DAS28-CRP at Week 24
Disease Activity Score 28 C-reactive protein score (DAS28-CRP) at Week 24 (Full Analysis Set). CRP samples were collected at Baseline and Weeks 8, 16 and 24. DAS28-CRP was calculated using the following equation: \[0.56\*Square Root (SQRT) (tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.36\*ln(CRP+1)\]\*1.10+1.15. Total DAS28-CRP scores were calculates and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and \<2.6. Low disease activity corresponds to 2.6 to \<3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.
Time frame: Baseline and Week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Change From Baseline in DAS28-CRP at Week 24 | -0.991 Score on a scale | Standard Deviation 1.1735 |
| MabThera | Change From Baseline in DAS28-CRP at Week 24 | -0.832 Score on a scale | Standard Deviation 0.8483 |
| Rituxan | Change From Baseline in DAS28-CRP at Week 24 | -0.861 Score on a scale | Standard Deviation 0.9488 |
Comparison: Least square means and confidence intervals (CIs) were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group onlyp-value: 0.240295% CI: [-0.422, 0.106]ANCOVA
Comparison: Least square means and CIs were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group onlyp-value: 0.134695% CI: [-0.469, 0.063]ANCOVA
Comparison: Least square means and CIs were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group onlyp-value: 0.742995% CI: [-0.314, 0.224]ANCOVA
Primary
Peak Plasma Concentration (Cmax) After Day 15 Infusion
Pharmacokinetic endpoint: Maximum Plasma Concentration (Cmax) after Day 15 infusion (Dose 2)
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Peak Plasma Concentration (Cmax) After Day 15 Infusion | 406.0 µg/mL | Geometric Coefficient of Variation 28.3 |
| MabThera | Peak Plasma Concentration (Cmax) After Day 15 Infusion | 427.7 µg/mL | Geometric Coefficient of Variation 28.3 |
| Rituxan | Peak Plasma Concentration (Cmax) After Day 15 Infusion | 411.1 µg/mL | Geometric Coefficient of Variation 24.5 |
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [89.03, 101.23]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [92.61, 105.3]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [97.54, 110.95]
Primary
Trough Concentration (Ctrough) Before the Second Infusion on Day 15
Pharmacokinetic endpoint: Trough concentration (Ctrough) before the second infusion on Day 15 (Dose 2). Trough (pre-dose) concentration prior to second infusion on Day 15 obtained directly from the observed concentration versus time data.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1 and 2 (Pre-dose 2). Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. Ctrough could not be determined for 11 participants in the SAIT101 arm, 12 participants in the MabThera arm and 16 participants in the Rituxan arm as samples were collected outside of a 312 to 360 hour window.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Trough Concentration (Ctrough) Before the Second Infusion on Day 15 | 60.35 µg/mL | Geometric Coefficient of Variation 40.3 |
| MabThera | Trough Concentration (Ctrough) Before the Second Infusion on Day 15 | 67.75 µg/mL | Geometric Coefficient of Variation 36.2 |
| Rituxan | Trough Concentration (Ctrough) Before the Second Infusion on Day 15 | 58.84 µg/mL | Geometric Coefficient of Variation 97.9 |
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [77.2, 102.79]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [88.72, 118.56]
Comparison: The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance (ANOVA) model with fixed effect for treatment90% CI: [99.51, 133.21]
Secondary
American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52
American Collage of Rheumatology (ACR) 20% response criteria (ACR20) response rates were assessed at Baseline and Weeks 8, 16, 24, 36 and 52. An ACR20 response is defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 36 | 63 participants |
| SAIT101 | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 24 | 36 participants |
| SAIT101 | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 8 | 39 participants |
| SAIT101 | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 16 | 50 participants |
| SAIT101 | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 52 (EOS) | 60 participants |
| MabThera | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 24 | 31 participants |
| MabThera | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 8 | 33 participants |
| MabThera | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 16 | 54 participants |
| MabThera | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 36 | 47 participants |
| MabThera | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 52 (EOS) | 49 participants |
| Rituxan | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 52 (EOS) | 59 participants |
| Rituxan | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 36 | 58 participants |
| Rituxan | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 8 | 44 participants |
| Rituxan | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 24 | 34 participants |
| Rituxan | American Collage of Rheumatology 20% Response Criteria (ACR20) Response Rates at Weeks 8, 16, 24, 36 and 52 | ACR20 Week 16 | 53 participants |
Comparison: Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.95% CI: [-4.74, 23.03]
Comparison: Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.95% CI: [-15.95, 11.22]
Comparison: Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method.95% CI: [-25.47, 2.45]
Secondary
American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52
Efficacy endpoint: American Collage of Rheumatology 50% response criteria (ACR50) response rates and American Collage of Rheumatology 70% response criteria (ACR70) at weeks 8, 16, 24, 36 and 52. An ACR50 response is defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). An ACR70 response is defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[Health Assessment Questionnaire (HAQ)\], visual analogue pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 8 | 13 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 8 | 2 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 16 | 17 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 16 | 9 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 24 | 15 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 24 | 8 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 36 | 37 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 36 | 19 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 52 (EOS) | 35 participants |
| SAIT101 | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 52 (EOS) | 23 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 52 (EOS) | 25 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 8 | 11 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 24 | 2 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 24 | 8 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 8 | 2 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 52 (EOS) | 13 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 36 | 6 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 16 | 16 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 36 | 19 participants |
| MabThera | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 16 | 4 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 36 | 12 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 16 | 5 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 24 | 5 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 24 | 3 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 52 (EOS) | 30 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 36 | 25 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 8 | 14 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 52 (EOS) | 17 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR70 Week 8 | 2 participants |
| Rituxan | American Collage of Rheumatology 50% Response Criteria (ACR50) Response Rates and American Collage of Rheumatology 70% Response Criteria (ACR70) at Weeks 8, 16, 24, 36 and 52 | ACR50 Week 16 | 14 participants |
Comparison: ACR20 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.95% CI: [-4.07, 22.46]
Comparison: ACR50 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.95% CI: [-10.22, 17.03]
Comparison: ACR50 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.95% CI: [-19.1, 7.51]
Comparison: ACR70 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.95% CI: [-1.52, 21.22]
Comparison: ACR70 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.95% CI: [-6.69, 17.13]
Comparison: ACR70 Week 52 (EOS) assessment. The 95% CIs for ACR response rate and difference were derived using the Wilson Score method. The adjusted difference and its 95% confidence intervals are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP value as a covariate.92% CI: [-15.68, 6.41]
Secondary
Apparent Terminal Rate Constant (λz)
Pharmacokinetic endpoint: Apparent terminal rate constant (λz) determined by linear regression of the terminal points of the log-linear concentration-time curve. Best fit method followed by visual assessment was used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points was used for determination.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. λz could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 1 participant in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality (RSQ) was \<0.800.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Apparent Terminal Rate Constant (λz) | 0.002358 1/hr | Standard Deviation 0.00061132 |
| MabThera | Apparent Terminal Rate Constant (λz) | 0.002283 1/hr | Standard Deviation 0.00067311 |
| Rituxan | Apparent Terminal Rate Constant (λz) | 0.002240 1/hr | Standard Deviation 0.00059435 |
Secondary
Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12))
Pharmacokinetic endpoint: Area under the concentration time curve Day 0 to Week 12 calculated by linear up/log down trapezoidal summation.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8 and 12. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. AUC0-w12 could not be determined for 1 participant in the SAIT101 arm, 4 participants in the MabThera arm and 1 participant in the Rituxan arm because samples were missing
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12)) | 148500 h*µg/mL | Geometric Coefficient of Variation 33.1 |
| MabThera | Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12)) | 157400 h*µg/mL | Geometric Coefficient of Variation 30.3 |
| Rituxan | Area Under the Concentration Time Curve Day 0 to Week 12 (AUC(0-w12)) | 155900 h*µg/mL | Geometric Coefficient of Variation 33.1 |
Secondary
Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24)
Pharmacokinetic endpoint: Area under the concentration time curve week 2 to week 24 (AUC(w2-24) calculated by linear up/log down trapezoidal summation.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. AUC0-w24 could not be determined for 30 participants in the SAIT101 arm, 32 participants in the MabThera arm and 28 participants either in the Rituxan arm as either there was no concentration at the start and/or end time, the Week 24 sample was out of window or samples were missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24) | 107300 h*µg/mL | Geometric Coefficient of Variation 41.1 |
| MabThera | Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24) | 109200 h*µg/mL | Geometric Coefficient of Variation 40 |
| Rituxan | Area Under the Concentration Time Curve Week 2 to Week 24 (AUC(w2-24) | 116000 h*µg/mL | Geometric Coefficient of Variation 40.2 |
Secondary
Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52
Disease Activity Score 28- Erythrocyte Sedimentation Rate (DAS28-ESR) consisted of tender joint counts (TJC), swollen joint counts (SJC) & erythrocyte sedimentation rate (ESR). The formula is: \[0.56\*SQRT(tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.7\*ln(ESR)\]+0.014\*patient global health assessment. Total DAS28-ESR scores are presented. Total scores range from 2 (minimum) to 10 (maximum). A lower score represents a better patient outcome. A DAS28-ESR of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Day 1 | 6.537 score on a scale | Standard Deviation 0.844 |
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 8 | 5.330 score on a scale | Standard Deviation 1.0649 |
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 16 | 4.861 score on a scale | Standard Deviation 1.1876 |
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 24 | 5.216 score on a scale | Standard Deviation 1.251 |
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 36 | 4.319 score on a scale | Standard Deviation 1.2798 |
| SAIT101 | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 52 (EOS) | 4.435 score on a scale | Standard Deviation 1.4375 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 52 (EOS) | 4.485 score on a scale | Standard Deviation 1.439 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Day 1 | 6.533 score on a scale | Standard Deviation 0.0781 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 24 | 5.410 score on a scale | Standard Deviation 1.2344 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 36 | 4.689 score on a scale | Standard Deviation 1.0077 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 8 | 5.315 score on a scale | Standard Deviation 1.2478 |
| MabThera | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 16 | 5.059 score on a scale | Standard Deviation 1.1682 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 8 | 5.235 score on a scale | Standard Deviation 1.2578 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 16 | 4.957 score on a scale | Standard Deviation 1.1802 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 52 (EOS) | 4.391 score on a scale | Standard Deviation 1.3947 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 24 | 5.432 score on a scale | Standard Deviation 1.1891 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Day 1 | 6.480 score on a scale | Standard Deviation 0.7577 |
| Rituxan | Change From Baseline DAS28-erythrocyte Sedimentation Rate (ESR) at Weeks 8, 16, 24, 36 and 52 | DAS28-ESR Week 36 | 4.499 score on a scale | Standard Deviation 1.198 |
Comparison: Week 52 ( EOS) Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.p-value: 0.924995% CI: [-0.375, 0.413]ANCOVA
Comparison: Week 52 ( EOS) Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.p-value: 0.0595% CI: [-0.351, 0.442]ANCOVA
Comparison: Week 52 ( EOS) Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline DAS28-ESR value as a covariate. ANCOVA model contains treatment group only.p-value: 0.896295% CI: [-0.376, 0.43]ANCOVA
Secondary
Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52
Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) samples taken at Baseline and Weeks 8, 16, 24, 36 and 52. DAS28-CRP was calculated using the following equation: \[0.56\*Square Root (SQRT) (tender 28 joint count)+0.28\*SQRT(swollen 28 joint count)+0.36\*ln(CRP+1)\]\*1.10+1.15. Total DAS28-CRP scores are presented and range from 2.0 (minimum) to 10 (maximum). Lower scores represent a better patient outcome. Disease remission is considered achieved if the score is between 0 and \<2.6. Low disease activity corresponds to 2.6 to \<3.2. Moderate activity is between 3.2 & ≤5.1, while high activity is above 5.1.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Day 1 (Baseline) | 5.282 score on a scale | Standard Deviation 0.8899 |
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 8 | 4.405 score on a scale | Standard Deviation 1.0189 |
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 16 | 4.001 score on a scale | Standard Deviation 1.1116 |
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 24 | 4.300 score on a scale | Standard Deviation 1.0331 |
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 36 | 3.552 score on a scale | Standard Deviation 1.1452 |
| SAIT101 | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 52 (End of Study( | 3.660 score on a scale | Standard Deviation 1.2636 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 52 (End of Study( | 3.754 score on a scale | Standard Deviation 1.3037 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Day 1 (Baseline) | 5.288 score on a scale | Standard Deviation 0.8073 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 24 | 4.463 score on a scale | Standard Deviation 1.0648 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 36 | 3.823 score on a scale | Standard Deviation 0.929 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 8 | 4.324 score on a scale | Standard Deviation 1.1132 |
| MabThera | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 16 | 4.155 score on a scale | Standard Deviation 0.975 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 8 | 4.251 score on a scale | Standard Deviation 1.1392 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 16 | 4.100 score on a scale | Standard Deviation 1.0044 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 52 (End of Study( | 3.518 score on a scale | Standard Deviation 1.1276 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 24 | 4.443 score on a scale | Standard Deviation 0.9774 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Day 1 (Baseline) | 5.170 score on a scale | Standard Deviation 0.8326 |
| Rituxan | Change From Baseline in DAS28-CRP at Weeks 8, 16, 36 and 52 | Week 36 | 3.716 score on a scale | Standard Deviation 1.0684 |
Comparison: Week 52 (EOS). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.p-value: 0.606895% CI: [-0.428, 0.25]ANCOVA
Comparison: Week 52 (EOS) Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.p-value: 0.59995% CI: [-0.249, 0.43]ANCOVA
Comparison: Week 53 (EOS) MabThera vs Rituxan. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and Baseline DAS28-CRP value as a covariate. ANCOVA model contains treatment group only.p-value: 0.305395% CI: [-0.165, 0.532]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level
C-reactive protein (CRP) level (Mg/L). CRP is a marker for inflammation. a normal reading is \<3 Mg/L. Higher values indicate disease related inflammation and increased cardiovascular risk. CRP levels between 3 Mg/L and 10 Mg/L are mildly elevated. Levels between 10 Mg/L and 100 Mg/L are moderately elevated and CRP levels above 100 Mg/L are severely elevated.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Day 1 | 19.5 Mg/L | Standard Deviation 28.99 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 8 | 12.5 Mg/L | Standard Deviation 15.78 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 16 | 8.5 Mg/L | Standard Deviation 11.78 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 24 | 9.5 Mg/L | Standard Deviation 14.54 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 36 | 8.0 Mg/L | Standard Deviation 20.33 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 52 (EOS) | 9.8 Mg/L | Standard Deviation 14.14 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 52 (EOS) | 9.1 Mg/L | Standard Deviation 14.93 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Day 1 | 15.3 Mg/L | Standard Deviation 20.63 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 24 | 8.3 Mg/L | Standard Deviation 14.4 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 36 | 7.0 Mg/L | Standard Deviation 10.38 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 8 | 12.3 Mg/L | Standard Deviation 20.29 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 16 | 7.2 Mg/L | Standard Deviation 9.02 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 8 | 10.4 Mg/L | Standard Deviation 12.78 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 16 | 7.3 Mg/L | Standard Deviation 6.9 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 52 (EOS) | 7.4 Mg/L | Standard Deviation 11.34 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 24 | 7.9 Mg/L | Standard Deviation 10.35 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Day 1 | 16.2 Mg/L | Standard Deviation 17.91 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: C-reactive Protein (CRP) Level | CRP Week 36 | 7.1 Mg/L | Standard Deviation 9.72 |
Comparison: Week 52 (EOS) CRP. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.818395% CI: [-4.113, 3.253]ANCOVA
Comparison: Week 52 (EOS) CRP. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.418695% CI: [-2.164, 5.191]ANCOVA
Comparison: Week 52 (EOS) CRP. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.303595% CI: [-1.768, 5.655]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI])
the Health Assessment Questionnaire-Disability Index (HAQ-DI) contains 20 questions split into 8 categories (dressing & grooming, arising, eating, walking, hygiene, reach, grip & activities). Scores were: 0 = Without ANY Difficulty; 1 = With SOME Difficulty; 2 = With MUCH Difficulty; 3 = UNABLE to Do. Total scores were calculated as the summed category scores divided by the number of categories. Total HAQ-DI scores are presented which range from 0 to 3. Higher scores represent a worse outcome. Scores of 0 to 1 represent mild to moderate difficulty, 1 to 2 moderate disability, and 2 to 3 severe to very severe disability.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Day 1 | 1.610 score on a scale | Standard Deviation 0.5728 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 8 | 1.168 score on a scale | Standard Deviation 0.6318 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 16 | 1.129 score on a scale | Standard Deviation 0.5775 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 24 | 1.209 score on a scale | Standard Deviation 0.6071 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 36 | 0.994 score on a scale | Standard Deviation 0.622 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 52 (EOS) | 1.027 score on a scale | Standard Deviation 0.6208 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 52 (EOS) | 1.207 score on a scale | Standard Deviation 0.7025 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Day 1 | 1.605 score on a scale | Standard Deviation 0.6567 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 24 | 1.335 score on a scale | Standard Deviation 0.6381 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 36 | 1.182 score on a scale | Standard Deviation 0.6883 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 8 | 1.314 score on a scale | Standard Deviation 0.6919 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 16 | 1.246 score on a scale | Standard Deviation 0.6394 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 8 | 1.176 score on a scale | Standard Deviation 0.6398 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 16 | 1.152 score on a scale | Standard Deviation 0.6668 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 52 (EOS) | 1.190 score on a scale | Standard Deviation 0.7116 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 24 | 1.294 score on a scale | Standard Deviation 0.6594 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Day 1 | 1.585 score on a scale | Standard Deviation 0.6421 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]) | HAQ-DI Week 36 | 1.061 score on a scale | Standard Deviation 0.6247 |
Comparison: Week 52 (EOS) HAQ-DI (0-3). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.050595% CI: [-0.339, 0]ANCOVA
Comparison: Week 52 (EOS) HAQ-DI (0-3). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.114195% CI: [-0.307, 0.033]ANCOVA
Comparison: Week 52 (EOS) HAQ-DI )0-3). Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.711195% CI: [-0.139, 0.204]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS])
Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]). Participants assessment of pain (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]) where 0 = no pain and 100 = severe pain.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Day 1 | 67.0 score on a scale | Standard Deviation 18.71 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 8 | 48.4 score on a scale | Standard Deviation 22.79 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 16 | 42.7 score on a scale | Standard Deviation 23.34 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 24 | 49.3 score on a scale | Standard Deviation 24.15 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 36 | 36.8 score on a scale | Standard Deviation 24.56 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 52 (EOS) | 41.2 score on a scale | Standard Deviation 24.34 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 52 (EOS) | 43.2 score on a scale | Standard Deviation 24.42 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Day 1 | 68.8 score on a scale | Standard Deviation 20.02 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 24 | 51.6 score on a scale | Standard Deviation 21.44 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 36 | 44.9 score on a scale | Standard Deviation 23.78 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 8 | 50.4 score on a scale | Standard Deviation 22.4 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 16 | 44.6 score on a scale | Standard Deviation 20.91 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 8 | 47.9 score on a scale | Standard Deviation 23.03 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 16 | 44.4 score on a scale | Standard Deviation 22.91 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 52 (EOS) | 44.5 score on a scale | Standard Deviation 26.1 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 24 | 51.8 score on a scale | Standard Deviation 23.58 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Day 1 | 68.8 score on a scale | Standard Deviation 19.27 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Assessment of Pain (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Assessment of Pain Week 36 | 41.6 score on a scale | Standard Deviation 23.46 |
Comparison: Week 52 (EOS) Participants Pain Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.732295% CI: [-8.0302, 5.841]ANCOVA
Comparison: Week 52 (EOS) Participants Pain Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.541895% CI: [-9.347, 4.92]ANCOVA
Comparison: Week 52 (EOS) Participants Pain Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline).p-value: 0.786995% CI: [-8.136, 6.169]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS)
Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants global assessment of disease activity (assessed on 1 to 100 mm visual analogue scale \[VAS\]). Patients rate how their Rheumatoid Arthritis has affected them, where 0 = very well and 100 = very poor.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Day 1 | 68.9 score on a scale | Standard Deviation 15.87 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 8 | 46.9 score on a scale | Standard Deviation 22.57 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 16 | 43.9 score on a scale | Standard Deviation 21.47 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 24 | 50.8 score on a scale | Standard Deviation 23.16 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 36 | 35.7 score on a scale | Standard Deviation 22.63 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 52 (EOS) | 41.4 score on a scale | Standard Deviation 23.02 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 52 (EOS) | 42.4 score on a scale | Standard Deviation 24.1 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Day 1 | 67.6 score on a scale | Standard Deviation 17.53 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 24 | 51.1 score on a scale | Standard Deviation 20.49 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 36 | 42.7 score on a scale | Standard Deviation 22.54 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 8 | 49.1 score on a scale | Standard Deviation 22.98 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 16 | 44.4 score on a scale | Standard Deviation 21.63 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 8 | 48.5 score on a scale | Standard Deviation 22.93 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 16 | 44.2 score on a scale | Standard Deviation 22.82 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 52 (EOS) | 43.1 score on a scale | Standard Deviation 23.93 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 24 | 52.3 score on a scale | Standard Deviation 21.9 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Day 1 | 70.8 score on a scale | Standard Deviation 17.04 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Participants Global Assessment of Disease Activity (Assessed on 1 to 100 mm VAS) | Disease activity Week 36 | 42.5 score on a scale | Standard Deviation 23.7 |
Comparison: Week 52 (EOS) Participants Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)p-value: 0.709795% CI: [-8.062, 5.496]ANCOVA
Comparison: Week 52 (EOS) Participants Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)p-value: 0.668395% CI: [-8.28, 5.317]ANCOVA
Comparison: Week 52 (EOS) Participants Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)p-value: 0.954895% CI: [-7.078, 6.682]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS])
Efficacy endpoint: Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians global assessment of disease activity (assessed on 1 to 100 mm Visual Analog Scale \[VAS\]). Where 0 = no disease activity and 100 = maximum disease activity.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activty iDay 1 | 71.0 score on a scale | Standard Error 14.3 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 8 | 45.6 score on a scale | Standard Error 20.75 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 16 | 39.2 score on a scale | Standard Error 20.94 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 24 | 47.9 score on a scale | Standard Error 22.28 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 36 | 30.3 score on a scale | Standard Error 21.56 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 52 (EOS) | 31.1 score on a scale | Standard Error 21.67 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 52 (EOS) | 35.1 score on a scale | Standard Error 23.49 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activty iDay 1 | 69.4 score on a scale | Standard Error 15 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 24 | 47.8 score on a scale | Standard Error 20.25 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 36 | 36.3 score on a scale | Standard Error 21.71 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 8 | 43.2 score on a scale | Standard Error 23.86 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 16 | 39.0 score on a scale | Standard Error 20.97 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 8 | 44.6 score on a scale | Standard Error 23.28 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 16 | 42.3 score on a scale | Standard Error 20.89 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 52 (EOS) | 31.2 score on a scale | Standard Error 22.95 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activity Week 24 | 49.0 score on a scale | Standard Error 22.45 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activty iDay 1 | 69.8 score on a scale | Standard Error 14.32 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Physicians Global Assessment of Disease Activity (Assessed on 1 to 100 mm Visual Analog Scale [VAS]) | Disease Activtiy Week 36 | 31.4 score on a scale | Standard Error 20.69 |
Comparison: Week 52 (EOS) Physician's Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baseline)p-value: 0.200895% CI: [-10.541, 2.226]ANCOVA
Comparison: Week 52 (EOS) Physician's Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baselinep-value: -0.3995% CI: [-6.771, 5.994]ANOVA
Comparison: Week 52 (EOS) Physician's Disease Activity Assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate. Change from Study Day 1 (Baselinep-value: 0.249895% CI: [-2.665, 10.204]ANCOVA
Secondary
Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System)
Efficacy endpoint: Individual components of the ACR improvement criteria on Day 1 and at weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and tender joint count (TJC) (the 66/68 joint count system). SJC and TJC assess the level of skeletal disease involvement. The 66/68 Joint Count evaluates 66 joints for swelling and 68 joints for tenderness.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Day 1 | 15.2 Joints | Standard Deviation 7.97 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 8 | 8.6 Joints | Standard Deviation 7.11 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 16 | 6.5 Joints | Standard Deviation 4.86 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 24 | 8.5 Joints | Standard Deviation 5.13 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 36 | 4.8 Joints | Standard Deviation 6.21 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 52 (EOS) | 5.2 Joints | Standard Deviation 6.53 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Day 1 | 21.7 Joints | Standard Deviation 11.08 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 8 | 13.9 Joints | Standard Deviation 9.94 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Week 16 | 11.1 Joints | Standard Deviation 10.24 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 24 | 13.6 Joints | Standard Deviation 9.79 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 36 | 8.3 Joints | Standard Deviation 9.1 |
| SAIT101 | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 52 (EOS) | 9.3 Joints | Standard Deviation 9.34 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 52 (EOS) | 11.9 Joints | Standard Deviation 15.18 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Day 1 | 15.2 Joints | Standard Deviation 15.2 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Day 1 | 22.6 Joints | Standard Deviation 13.66 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Week 16 | 12.5 Joints | Standard Deviation 8.36 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 8 | 8.4 Joints | Standard Deviation 6.62 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 52 (EOS) | 6.5 Joints | Standard Deviation 9.46 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 36 | 10.9 Joints | Standard Deviation 10.68 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 16 | 7.8 Joints | Standard Deviation 7.2 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 8 | 14.0 Joints | Standard Deviation 9.94 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 36 | 5.4 Joints | Standard Deviation 5.72 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 24 | 10.0 Joints | Standard Deviation 5.85 |
| MabThera | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 24 | 15.6 Joints | Standard Deviation 11.94 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 24 | 10.0 Joints | Standard Deviation 6.19 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 36 | 5.7 Joints | Standard Deviation 5.49 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 24 | 15.2 Joints | Standard Deviation 11.62 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 52 (EOS) | 4.6 Joints | Standard Deviation 5.04 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Day 1 | 20.0 Joints | Standard Deviation 10.84 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 8 | 13.5 Joints | Standard Deviation 10.69 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 36 | 9.6 Joints | Standard Deviation 10.81 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Day 1 | 13.0 Joints | Standard Deviation 6.19 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count Week 8 | 7.7 Joints | Standard Deviation 5.92 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Count Week 16 | 11.8 Joints | Standard Deviation 9.09 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Swollen Joint Count 16 | 7.0 Joints | Standard Deviation 5.37 |
| Rituxan | Individual Components of the ACR Improvement Criteria on Day 1 and at Weeks 8, 16, 24, 36 and 52: Swollen Joint Count (SJC) and Tender Joint Count (TJC) (the 66/68 Joint Count System) | Tender Joint Score Week 52 (EOS) | 9.4 Joints | Standard Deviation 11.41 |
Comparison: Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: 0.199795% CI: [-3.23, 0.671]ANCOVA
Comparison: Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: 0.909895% CI: [-2.074, 1.848]ANCOVA
Comparison: Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: 0.24895% CI: [-0.817, 3.15]ANCOVA
Comparison: Tender Joint Count (TJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: 0.193195% CI: [-4.909, 0.996]ANCOVA
Comparison: Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: -0.7795% CI: [-3.722, 2.184]ANCOVA
Comparison: Swollen Joint Count (SJC) Week 52 (EOS) assessment. Least square means and confidence intervals were estimated from an ANCOVA model containing treatment group as a factor and baseline value as a covariate.p-value: 0.435295% CI: [-1.805, 4.18]ANCOVA
Secondary
Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52
Number if Participants with a Clinical Remission Response (CRR) defined by the Simplified Disease Activity Index (SDAI) \<3.3 at weeks 8, 16, 24, 36 and 52 (EOS).
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 8 | 0 participants |
| SAIT101 | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 36 | 2 participants |
| SAIT101 | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 24 | 0 participants |
| SAIT101 | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 52 (EOS) | 1 participants |
| SAIT101 | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 16 | 0 participants |
| MabThera | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 52 (EOS) | 2 participants |
| MabThera | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 8 | 0 participants |
| MabThera | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 16 | 1 participants |
| MabThera | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 24 | 1 participants |
| MabThera | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 36 | 0 participants |
| Rituxan | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 16 | 0 participants |
| Rituxan | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 52 (EOS) | 2 participants |
| Rituxan | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 36 | 1 participants |
| Rituxan | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 8 | 0 participants |
| Rituxan | Number of Participants With a Clinical Remission Response (CRR) at Weeks 8, 16, 24, 36 and 52 | CRR Week 24 | 0 participants |
Comparison: Week 52 (EOS). Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-6.9, 3.9]
Comparison: Week 52 (EOS). Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-7.07, 3.86]
Comparison: Week 52 (EOS). Clinical remission is defined as score of Simplified Disease Activity Index (SDAI) smaller than 3.3. The 95% CIs for clinical remission rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-6.05, 5.83]
Secondary
Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks
Efficacy endpoint: number of participants with a major clinical response defined as a continuous ACR70 from Baseline (Day 1) for at least 24 weeks. ACR70 is a measure based on American College of Rheumatology criteria of at least a 70% improvement in the number of tender and swollen joints, and a 70% improvement in at least 3 of the following: the patient's global assessment of disease status; the patient's assessment of pain; the patient's assessment of function measured using the Stanford Health Assessment Questionnaire the physician's global assessment of disease status; serum C-reactive protein levels.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 24 | 1 participants |
| SAIT101 | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 52 (EOS) | 2 participants |
| MabThera | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 24 | 0 participants |
| MabThera | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 52 (EOS) | 0 participants |
| Rituxan | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 24 | 0 participants |
| Rituxan | Number of Participants With a Major Clinical Response (Continuous ACR70) for at Least 24 Weeks | Major Clinical Response Week 52 (EOS) | 1 participants |
Comparison: Week 52 (EOS) Major Clinical Response. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-2.56, 7.83]
Comparison: Week 52 (EOS) Major Clinical Response. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-4.74, 6.67]
Comparison: Week 52 (EOS) Major Clinical Response. The 95% CIs for major clinical response rate and treatment difference were derived using the Wilson Score method. The adjusted difference and its 95% CI are from a logistic regression model containing treatment group as a factor and baseline DAS28-CRP as a covariate.95% CI: [-6.75, 3.39]
Secondary
Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels)
Change from baseline (Day 1) in immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) levels (mg/dL) at Week 8, 16, 24 36 and 52 (End of study)
Time frame: Baseline (Day 1) and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Pharmacodynamic Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Screening | 321.1 Mg/dL | Standard Deviation 269.22 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 36 | 1076.6 Mg/dL | Standard Deviation 246.62 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 8 | 293.6 Mg/dL | Standard Deviation 176.04 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 16 | 301.8 Mg/dL | Standard Deviation 204.14 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 52 (EOS) | 1102.0 Mg/dL | Standard Deviation 274.44 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 24 | 279.8 Mg/dL | Standard Deviation 119.87 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 36 | 283.8 Mg/dL | Standard Deviation 204.12 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 8 | 1108.0 Mg/dL | Standard Deviation 242.2 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 52 | 269.4 Mg/dL | Standard Deviation 116.74 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Screening | 1231.0 Mg/dL | Standard Deviation 299.36 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Screening | 164.3 Mg/dL | Standard Deviation 76.07 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 16 | 1105.2 Mg/dL | Standard Deviation 232.51 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 8 | 137.5 Mg/dL | Standard Deviation 71.38 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 16 | 123.7 Mg/dL | Standard Deviation 61.08 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 24 | 123.3 Mg/dL | Standard Deviation 62.37 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 24 | 1114.6 Mg/dL | Standard Deviation 251.78 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 36 | 111.7 Mg/dL | Standard Deviation 56.89 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 52 (EOS) | 109.6 Mg/dL | Standard Deviation 56.8 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 24 | 117.1 Mg/dL | Standard Deviation 80.96 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Screening | 283.4 Mg/dL | Standard Deviation 134.8 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Screening | 167.9 Mg/dL | Standard Deviation 100.16 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Screening | 1230.1 Mg/dL | Standard Deviation 365.54 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 8 | 264.4 Mg/dL | Standard Deviation 121.41 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 36 | 1060.9 Mg/dL | Standard Deviation 305.12 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 52 (EOS) | 107.6 Mg/dL | Standard Deviation 77 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 16 | 253.0 Mg/dL | Standard Deviation 111.58 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 8 | 132.6 Mg/dL | Standard Deviation 83.58 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 16 | 1075.7 Mg/dL | Standard Deviation 277.51 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 24 | 263.0 Mg/dL | Standard Deviation 121.15 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 52 (EOS) | 1081.1 Mg/dL | Standard Deviation 285.13 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 36 | 108.0 Mg/dL | Standard Deviation 77.79 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 36 | 259.2 Mg/dL | Standard Deviation 116.55 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 16 | 124.9 Mg/dL | Standard Deviation 85.71 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 8 | 1080.6 Mg/dL | Standard Deviation 279.75 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 52 | 254.7 Mg/dL | Standard Deviation 115.38 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 24 | 1077.2 Mg/dL | Standard Deviation 265.55 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 52 | 297.8 Mg/dL | Standard Deviation 138.63 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Screening | 1203.4 Mg/dL | Standard Deviation 373.29 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 8 | 1038.5 Mg/dL | Standard Deviation 290.01 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 36 | 976.6 Mg/dL | Standard Deviation 249.11 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 16 | 1038.5 Mg/dL | Standard Deviation 290.01 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 24 | 1023.2 Mg/dL | Standard Deviation 278.7 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgG Week 52 (EOS) | 999.9 Mg/dL | Standard Deviation 232.03 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Screening | 159.0 Mg/dL | Standard Deviation 81.36 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 8 | 128.9 Mg/dL | Standard Deviation 68.5 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 16 | 117.0 Mg/dL | Standard Deviation 60.44 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 24 | 109.9 Mg/dL | Standard Deviation 73.11 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 36 | 99.7 Mg/dL | Standard Deviation 56.38 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgM Week 52 (EOS) | 95.2 Mg/dL | Standard Deviation 52.57 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Screening | 342.9 Mg/dL | Standard Deviation 153.24 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 8 | 316.5 Mg/dL | Standard Deviation 146.15 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 16 | 312.7 Mg/dL | Standard Deviation 151.87 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 24 | 307.7 Mg/dL | Standard Deviation 147.92 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in Immunoglobulin (IgG, IgM and IgA Levels) | IgA Week 36 | 297.1 Mg/dL | Standard Deviation 146.85 |
Secondary
Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52
Efficacy endpoint: Proportion of participants with European League Against Rheumatism (EULAR) response (defined as good response, moderate response or no response) at weeks 8, 16, 24 36 and 52 (EOS). EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The DAS28-CRP was classified into 3 categories: low disease activity (\<= 3.2), moderate disease activity (\> 3.2 and \<= 5.1) and high disease activity (\> 5.1). Good response was defined as \>1.2 improvement in the DAS28-CRP from baseline with low disease activity.
Time frame: Baseline and Weeks 8, 16, 24, 36 and 52 (EOS)
Population: Full Analysis Set (analyses are reported in terms of the arm that the patient was initially randomised into. In the Rituxan arm only, patients eligible for treatment in Part B underwent a second randomisation to receive either Rituxan or SAIT101 and are reported in the Rituxan arm according to their initial randomisation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good | 12 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good or Moderate | 30 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good | 20 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good or Moderate | 44 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good | 12 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good or Moderate | 30 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good | 27 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good or Moderate | 58 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good | 34 participants |
| SAIT101 | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good or Moderate | 59 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good | 31 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good | 14 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good or Moderate | 26 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good | 7 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good or Moderate | 33 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good or Moderate | 50 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good or Moderate | 50 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good | 12 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good | 15 participants |
| MabThera | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good or Moderate | 42 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good or Moderate | 54 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good or Moderate | 33 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good | 7 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 24 Good or Moderate | 23 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good | 32 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 36 Good | 27 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good | 12 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 52 (EOS) Good or Moderate | 63 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 8 Good or Moderate | 33 participants |
| Rituxan | Proportion of Participants With European League Against Rheumatism (EULAR) Response at Weeks 8, 16, 24 36 and 52 | Week 16 Good | 13 participants |
Comparison: Week 52 EULAR score 'Good'. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.95% CI: [-12.59, 15.1]
Comparison: Week 52 EULAR score 'Good'. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.95% CI: [-13.75, 14.03]Difference (%)
Comparison: Week 52 EULAR score 'Good'. EULAR (European League Against Rheumatism) response was classified using the individual amount of change in the DAS28-CRP score. The 95% CIs for EULAR response rate and treatment difference were derived using the Wilson Score method.95% CI: [-15.14, 12.91]
Secondary
Systemic Clearance (CL)
Pharmacokinetic endpoint: Systemic clearance (CL) over the first dosing period calculated as dose (first + second dose) divided by AUC(0-∞).
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. CL could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality (RSQ) was \<0.800.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Systemic Clearance (CL) | 0.01314 L/day | Geometric Coefficient of Variation 34.6 |
| MabThera | Systemic Clearance (CL) | 0.01235 L/day | Geometric Coefficient of Variation 29 |
| Rituxan | Systemic Clearance (CL) | 0.01240 L/day | Geometric Coefficient of Variation 33.3 |
Secondary
Terminal Half-life (T1/2)
Pharmacokinetic endpoint: Terminal half-life determined as ln2/λz.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. T1/2 could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 1 participant in the Rituxan arm as either the terminal was undetermined or the Regulatory Scientific Quality was \<0.800.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Terminal Half-life (T1/2) | 303.7 Hours | Geometric Coefficient of Variation 26.1 |
| MabThera | Terminal Half-life (T1/2) | 316.1 Hours | Geometric Coefficient of Variation 29 |
| Rituxan | Terminal Half-life (T1/2) | 319.7 Hours | Geometric Coefficient of Variation 26.2 |
Secondary
Time to Maximum Plasma Concentration (Tmax) (Dose 1)
Pharmacokinetic endpoint: Maximum plasma concentration over the first dosing interval obtained directly from the observed concentration versus time data.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. Tmax (dose 1) could not be determined for 1 participant in the SAIT101 arm, 1 patient in the MabThera arm and 2 participants in the Rituxan arm as samples were missing or set to missing due to initial or embedded Below the Limit of Quantification (BLQ)..
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAIT101 | Time to Maximum Plasma Concentration (Tmax) (Dose 1) | 5.167 Hours |
| MabThera | Time to Maximum Plasma Concentration (Tmax) (Dose 1) | 5.167 Hours |
| Rituxan | Time to Maximum Plasma Concentration (Tmax) (Dose 1) | 4.500 Hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) (Dose 2)
Time of maximum concentration postinfusion over the second dosing interval, obtained directly from the observed concentration versus time data.
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAIT101 | Time to Maximum Plasma Concentration (Tmax) (Dose 2) | 4.167 Hours |
| MabThera | Time to Maximum Plasma Concentration (Tmax) (Dose 2) | 4.167 Hours |
| Rituxan | Time to Maximum Plasma Concentration (Tmax) (Dose 2) | 4.250 Hours |
Secondary
Volume of Distribution (VD)
Pharmacokinetic endpoint: Volume of distribution (VD) over the first dosing period calculated as dose (first + second dose) divided by \[λz AUC(0-∞)\]
Time frame: Samples for pharmacokinetic evaluation were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic Analysis Set. VD could not be determined for 1 participant in the SAIT101 arm, 2 participants in the MabThera arm and 2 participants in the Rituxan arm as either the terminal phase was undetermined or the Regulatory Scientific Quality was \<0.800.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Volume of Distribution (VD) | 5.757 Litres (L) | Geometric Coefficient of Variation 28 |
| MabThera | Volume of Distribution (VD) | 5.635 Litres (L) | Geometric Coefficient of Variation 23.6 |
| Rituxan | Volume of Distribution (VD) | 5.727 Litres (L) | Geometric Coefficient of Variation 22.9 |
Other Pre-specified
Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period
Pharmacodynamic endpoint: Descriptive statistics (mean \[SD\]) of the change from baseline in CD19+ B-cell count during the study period (Day 15 \[AUEC(0-d15\] and Week 24 \[AUEC(0-w24\])
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacodynamic Analysis Set. participants in the SAIT101 arm, Twenty three participants in the MabThera arm, 20 participants in the MabThera and 20 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline and / or the Week 24 assessment was missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-d15) | -2729 Cells*day/µL | Standard Deviation 1915.3 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-w24) | -33500 Cells*day/µL | Standard Deviation 23881 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-d15) | -2935 Cells*day/µL | Standard Deviation 2222.1 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-w24) | -36410 Cells*day/µL | Standard Deviation 22883 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-d15) | -2367 Cells*day/µL | Standard Deviation 1978.1 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in CD19+ B-cell Count During the Study Period | AUEC(0-w24) | -28500 Cells*day/µL | Standard Deviation 20878 |
Other Pre-specified
Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52
Pharmacodynamic endpoint: Change from baseline (Day 1) in C-reactive protein (CRP) levels (mg/dL) at weeks 8, 16, 24, 36 and 52 (EOS)
Time frame: Baseline (Day 1) and Weeks 8, 16, 24, 26 & 52 (EOS)
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 36 | 8.0 Mg/dL | Standard Deviation 10.33 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 16 | 8.5 Mg/dL | Standard Deviation 11.78 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 52 (EOS) | 9.8 Mg/dL | Standard Deviation 14.28 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Day 1 | 19.5 Mg/dL | Standard Deviation 29.5 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 24 | 9.5 Mg/dL | Standard Deviation 14.54 |
| SAIT101 | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 8 | 12.5 Mg/dL | Standard Deviation 15.78 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 24 | 8.3 Mg/dL | Standard Deviation 14.4 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 36 | 7.0 Mg/dL | Standard Deviation 10.38 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 8 | 12.3 Mg/dL | Standard Deviation 20.29 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 52 (EOS) | 9.1 Mg/dL | Standard Deviation 15.01 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Day 1 | 15.5 Mg/dL | Standard Deviation 20.76 |
| MabThera | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 16 | 7.2 Mg/dL | Standard Deviation 9.02 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 52 (EOS) | 7.3 Mg/dL | Standard Deviation 11.33 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Day 1 | 16.1 Mg/dL | Standard Deviation 17.64 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 8 | 10.4 Mg/dL | Standard Deviation 12.85 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 16 | 7.3 Mg/dL | Standard Deviation 6.9 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 24 | 7.9 Mg/dL | Standard Deviation 10.35 |
| Rituxan | Pharmacodynamic Endpoint: Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 8, 16, 24, 36 and 52 | CRP Week 36 | 7.1 Mg/dL | Standard Deviation 9.72 |
Other Pre-specified
Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24
Pharmacodynamic endpoint: proportion of participants (n) with depletion of CD19+ B-cell count up to week 24 (Pharmacodynamic analysis set).
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacokinetic data set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24 | 45 participants |
| MabThera | Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24 | 46 participants |
| Rituxan | Pharmacodynamic Endpoint: Depletion of B-lymphocyte Antigen CD19 (CD19+) B-cell Count up to Week 24 | 50 participants |
Other Pre-specified
Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion
Duration of CD19+ B-cell depletion (only participants that returned to non-depletion at or before week 24 were included)
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacodynamic Analysis Set.Pharmacodynamic Analysis Set. Fifty seven participants in the SAIT101 arm, 70 participants in the MabThera arm and 72 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline or if the Week 24 assessment was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion | 78.444 Days | Standard Deviation 77.529 |
| MabThera | Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion | 85.856 Days | Standard Deviation 73.446 |
| Rituxan | Pharmacodynamic Endpoint: Duration of CD19+ B-cell Depletion | 77.290 Days | Standard Deviation 72.0557 |
Other Pre-specified
Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline
Number of participants with CD19+ B-cell count recover versus baseline. Incidence of B-Cell recovery was defined as either CD19+ B-cell counts retuned to baseline or the lower limit or normal of 110 cells/µL at week 24).
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline | 5 Participants |
| MabThera | Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline | 4 Participants |
| Rituxan | Pharmacodynamic Endpoint: Number of Participants With CD19+ B-cell Count Recover Versus Baseline | 3 Participants |
Other Pre-specified
Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion
Time needed to CD19+ B-cell depletion in Part A (calculated as the first time CD19+ B-cell count below 20/µL minus time of first dosing in days).
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacodynamic Analysis Set. Two participants in the SAIT101 arm, 3 participants in the MabThera arm and 3 participants in the Rituxan arm were excluded from the analysis either as they had a depleted C-cell count at baseline and / or if the Week 24 assessment was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion | 1.524 Days | Standard Deviation 2.6274 |
| MabThera | Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion | 2.847 Days | Standard Deviation 9.1286 |
| Rituxan | Pharmacodynamic Endpoint: Time Needed to CD19+ B-cell Depletion | 2.223 Days | Standard Deviation 9.0833 |
Other Pre-specified
Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24
Area under the concentration time curve of CD19 B-cell count change at Day 15 (AUEC0-d15) and week 24 (AUEC0-w24) based on change from baseline and percent of baseline values
Time frame: Samples for pharmacodynamic evaluation (CD19+ B-cell) were taken at Baseline and Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36 and 52. Unscheduled visit samples were taken at the discretion of the investigator.
Population: Pharmacodynamic Analysis Set. AUC0-d15 could not be determined for 23 participants in the SAIT101 arm, 20 participants in the MabThera arm and 20 participants in the Rituxan arm as either the baseline data was missing and /or there was a missing b-cell could at the last timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SAIT101 | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-w24) | -32707.6 cells*day/µL) |
| SAIT101 | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-d15) | -2650.0 cells*day/µL) |
| MabThera | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-d15) | -2672.1 cells*day/µL) |
| MabThera | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-w24) | -33018.3 cells*day/µL) |
| Rituxan | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-d15) | -2719.4 cells*day/µL) |
| Rituxan | Pharmaco Endpoint: Area Under the Concentration Time Curve of CD19 B-cell Count Change at Day 15 and Week 24 | AUEC(0-w24) | -33003.7 cells*day/µL) |
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-137.1, 181.3]
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-91.8, 230.8]
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-112.5, 207.2]
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-187.9, 809.4]
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-213.8, 806.1]
Comparison: The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-527.4, 498.2]