Rheumatoid Arthritis
Conditions
Brief summary
The primary objective of this study is: \- To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA). The secondary objectives of this study are: * To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development. * To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.
Interventions
Sponsors
Ablynx, a Sanofi company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RA (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III. * Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use. * Subjects must not have received MTX for at least 4 weeks before first administration of the study drug. * Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline * Others as defined in the protocol
Exclusion criteria
* Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug. * Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase \[JAK\]-inhibitors) less than 6 months prior to screening. * Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs (including JAK inhibitors), for RA. * Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time. * Others as defined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 | Week 12 | ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12 | Week 12 | DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 | Week 12 | DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 | Week 12 | SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Low disease activity: 3.3 \< SDAI ≤ 11.0 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 | Week 12 | CDAI = TJC28 + SJC28 + VASPA + VASPHA Low disease activity: 2.8 \< CDAI ≤ 10 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 | Week 12 | EULAR good response is defined as an improvement of \>1.2 in DAS28 (CRP) relative to baseline. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 | Week 12 | DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Remission = DAS28(ESR) \< 2.6 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects in Remission Using SDAI at Week 12 | Week 12 | SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Remission: SDAI ≤ 3.3 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects in Remission Using CDAI at Week 12 | Week 12 | CDAI = TJC28 + SJC28 + VASPA + VASPHA Remission: CDAI ≤ 2.8 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 | Week 12 | Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders. |
| Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | Week 12 | ACR50/70 response is defined as: * 50/70% improvement in TJC (68 joints) relative to Week 0 AND * 50/70% improvement in SJC (66 joints) relative to Week 0 AND * 50/70% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 12 were treated as non-responders. |
| Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | From baseline until week 12 | The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Low score indicates greater disability. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 | From baseline until Week 12 | The FACIT Measurement System is a collection of health-related quality of life questionnaires that assess multidimensional health status in people with various chronic illnesses. The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue. |
| Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | From baseline until Week 12 | Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ). |
| Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12 | From baseline until Week 12 | — |
| Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU) | — |
| Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | From baseline until Week 12 | — |
| Number of Treatment-emergent Adverse Event by Severity | From baseline until Week 12 | — |
| Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event | From baseline until Week 12 | treatment related = considered at least possibly related to study drug by the Investigator |
| Number of Treatment-related Treatment-emergent Adverse Event | From baseline until Week 12 | treatment related = considered at least possibly related to study drug by the Investigator |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | From baseline until Week 12 | The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome). Missing values were imputed with the last non-missing observation. |
Countries
Belgium, Bulgaria, Czechia, Georgia, Germany, Hungary, Mexico, Moldova, North Macedonia, Poland, Romania, Serbia, Spain, United States
Participant flow
Recruitment details
A total of 251 subjects were recruited at 58 sites located in Europe (42 sites; 199 subjects), Latin America (6 sites; 36 subjects) and North America (10 sites; 16 subjects). Consent was obtained from the first subject on 18 Mar 2015; the last subject completed the final visit in on 19 Jul 2016.
Pre-assignment details
Of the 599 subjects screened, 348 were screen failures and 251 subjects were randomly assigned to treatment (Intent-to-treat population). All subjects enrolled received study treatment and were included in the safety population. All subjects who received at least one dose of ALX-0061 were included in the pharmacokinetic (PK) population.
Participants by arm
| Arm | Count |
|---|---|
| ALX-0061 150 mg q4w ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
ALX-0061
Placebo | 62 |
| ALX-0061 150 mg q2w ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
ALX-0061
Placebo | 62 |
| ALX-0061 225 mg q2w ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
ALX-0061 | 63 |
| TCZ 162 mg q1w or q2w Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).
Tocilizumab | 64 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 3 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Other | 1 | 0 | 2 | 0 |
| Overall Study | Sponsor's decision | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | ALX-0061 150 mg q4w | ALX-0061 150 mg q2w | ALX-0061 225 mg q2w | TCZ 162 mg q1w or q2w | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 12 Participants | 8 Participants | 7 Participants | 6 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 53 Participants | 56 Participants | 58 Participants | 217 Participants |
| Age, Continuous | 53.0 years STANDARD_DEVIATION 12.25 | 51.2 years STANDARD_DEVIATION 12.05 | 51.3 years STANDARD_DEVIATION 11.81 | 50.0 years STANDARD_DEVIATION 12.26 | 51.4 years STANDARD_DEVIATION 12.07 |
| Sex: Female, Male Female | 49 Participants | 53 Participants | 54 Participants | 56 Participants | 212 Participants |
| Sex: Female, Male Male | 13 Participants | 9 Participants | 9 Participants | 8 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 62 | 0 / 63 | 0 / 64 |
| other Total, other adverse events | 15 / 62 | 20 / 62 | 17 / 63 | 12 / 64 |
| serious Total, serious adverse events | 1 / 62 | 0 / 62 | 2 / 63 | 2 / 64 |
Outcome results
Primary
Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 | 45 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 | 48 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 | 51 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12 | 50 Participants |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12
The FACIT Measurement System is a collection of health-related quality of life questionnaires that assess multidimensional health status in people with various chronic illnesses. The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.
Time frame: From baseline until Week 12
Population: Intent-to-treat population, number of subjects with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALX-0061 150 mg q4w | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 | 7.832 score on a scale | Standard Error 1.3438 |
| ALX-0061 150 mg q2w | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 | 11.41 score on a scale | Standard Error 1.53 |
| ALX-0061 225 mg q2w | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 | 12.996 score on a scale | Standard Error 1.3702 |
| TCZ 162 mg q1w or q2w | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12 | 8.971 score on a scale | Standard Error 1.4461 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome). Missing values were imputed with the last non-missing observation.
Time frame: From baseline until Week 12
Population: Intent-to-treat population, number of participants with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALX-0061 150 mg q4w | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.541 score on a scale | Standard Error 0.0809 |
| ALX-0061 150 mg q2w | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.746 score on a scale | Standard Error 0.0935 |
| ALX-0061 225 mg q2w | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.817 score on a scale | Standard Error 0.0802 |
| TCZ 162 mg q1w or q2w | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.689 score on a scale | Standard Error 0.0811 |
Secondary
Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12
The Short Form (36) Health Survey (SF-36) consists of 36 items that can be summarized into 8 domains: physical functioning, role limitations due to physical health problems (role-physical), bodily pain, general health, vitality, social functioning, role limitations due to emotional problems (role-emotional), and mental health. Two summary measures, the physical component summary and the mental component summary, can be derived based on these domain scores. Each score is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Low score indicates greater disability.
Time frame: From baseline until week 12
Population: Intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 150 mg q4w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | physical component | 7.808 score on a scale | Standard Error 0.8533 |
| ALX-0061 150 mg q4w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | mental component | 5.49 score on a scale | Standard Error 1.221 |
| ALX-0061 150 mg q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | mental component | 8.836 score on a scale | Standard Error 1.5243 |
| ALX-0061 150 mg q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | physical component | 7.979 score on a scale | Standard Error 1.1895 |
| ALX-0061 225 mg q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | physical component | 8.861 score on a scale | Standard Error 1.0818 |
| ALX-0061 225 mg q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | mental component | 8.913 score on a scale | Standard Error 1.3903 |
| TCZ 162 mg q1w or q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | mental component | 6.156 score on a scale | Standard Error 1.3192 |
| TCZ 162 mg q1w or q2w | Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12 | physical component | 7.611 score on a scale | Standard Error 0.9562 |
Secondary
Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12
Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 | 2 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 | 3 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 | 4 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12 | 4 Participants |
Secondary
Number and Percentage of Subjects in Remission Using CDAI at Week 12
CDAI = TJC28 + SJC28 + VASPA + VASPHA Remission: CDAI ≤ 2.8 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects in Remission Using CDAI at Week 12 | 6 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects in Remission Using CDAI at Week 12 | 3 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects in Remission Using CDAI at Week 12 | 4 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects in Remission Using CDAI at Week 12 | 6 Participants |
Secondary
Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12
DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Remission = DAS28(ESR) \< 2.6 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 | 21 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 | 13 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 | 25 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12 | 16 Participants |
Secondary
Number and Percentage of Subjects in Remission Using SDAI at Week 12
SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Remission: SDAI ≤ 3.3 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects in Remission Using SDAI at Week 12 | 5 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects in Remission Using SDAI at Week 12 | 3 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects in Remission Using SDAI at Week 12 | 5 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects in Remission Using SDAI at Week 12 | 7 Participants |
Secondary
Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12
ACR50/70 response is defined as: * 50/70% improvement in TJC (68 joints) relative to Week 0 AND * 50/70% improvement in SJC (66 joints) relative to Week 0 AND * 50/70% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 12 were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR50 | 27 Participants |
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR70 | 10 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR70 | 15 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR50 | 23 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR50 | 31 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR70 | 13 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR50 | 29 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12 | ACR70 | 15 Participants |
Secondary
Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event
treatment related = considered at least possibly related to study drug by the Investigator
Time frame: From baseline until Week 12
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event | 21 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event | 20 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event | 21 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event | 20 Participants |
Secondary
Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
Time frame: From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 7 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 25 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 26 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 58 Participants |
Secondary
Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12
EULAR good response is defined as an improvement of \>1.2 in DAS28 (CRP) relative to baseline. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 | 25 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 | 34 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 | 38 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12 | 28 Participants |
Secondary
Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12
CDAI = TJC28 + SJC28 + VASPA + VASPHA Low disease activity: 2.8 \< CDAI ≤ 10 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 | 23 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 | 21 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 | 32 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12 | 21 Participants |
Secondary
Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12
DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 | 26 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 | 32 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 | 34 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12 | 20 Participants |
Secondary
Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12
SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Low disease activity: 3.3 \< SDAI ≤ 11.0 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 | 23 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 | 27 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 | 33 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12 | 22 Participants |
Secondary
Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12
DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.
Time frame: Week 12
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12 | 26 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12 | 35 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12 | 38 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12 | 28 Participants |
Secondary
Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity
Time frame: From baseline until Week 12
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Mild | 22 Participants |
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Severe | 0 Participants |
| ALX-0061 150 mg q4w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Moderate | 12 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Mild | 18 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Severe | 2 Participants |
| ALX-0061 150 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Moderate | 13 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Moderate | 9 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Mild | 21 Participants |
| ALX-0061 225 mg q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Severe | 1 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Mild | 19 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Severe | 2 Participants |
| TCZ 162 mg q1w or q2w | Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity | Moderate | 10 Participants |
Secondary
Number of Treatment-emergent Adverse Event by Severity
Time frame: From baseline until Week 12
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ALX-0061 150 mg q4w | Number of Treatment-emergent Adverse Event by Severity | Mild | 46 Treatment-emergent adverse events |
| ALX-0061 150 mg q4w | Number of Treatment-emergent Adverse Event by Severity | Severe | 0 Treatment-emergent adverse events |
| ALX-0061 150 mg q4w | Number of Treatment-emergent Adverse Event by Severity | Moderate | 18 Treatment-emergent adverse events |
| ALX-0061 150 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Mild | 75 Treatment-emergent adverse events |
| ALX-0061 150 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Severe | 2 Treatment-emergent adverse events |
| ALX-0061 150 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Moderate | 22 Treatment-emergent adverse events |
| ALX-0061 225 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Moderate | 15 Treatment-emergent adverse events |
| ALX-0061 225 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Mild | 84 Treatment-emergent adverse events |
| ALX-0061 225 mg q2w | Number of Treatment-emergent Adverse Event by Severity | Severe | 3 Treatment-emergent adverse events |
| TCZ 162 mg q1w or q2w | Number of Treatment-emergent Adverse Event by Severity | Mild | 47 Treatment-emergent adverse events |
| TCZ 162 mg q1w or q2w | Number of Treatment-emergent Adverse Event by Severity | Severe | 2 Treatment-emergent adverse events |
| TCZ 162 mg q1w or q2w | Number of Treatment-emergent Adverse Event by Severity | Moderate | 15 Treatment-emergent adverse events |
Secondary
Number of Treatment-related Treatment-emergent Adverse Event
treatment related = considered at least possibly related to study drug by the Investigator
Time frame: From baseline until Week 12
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALX-0061 150 mg q4w | Number of Treatment-related Treatment-emergent Adverse Event | 46 treatment-emergent adverse events |
| ALX-0061 150 mg q2w | Number of Treatment-related Treatment-emergent Adverse Event | 53 treatment-emergent adverse events |
| ALX-0061 225 mg q2w | Number of Treatment-related Treatment-emergent Adverse Event | 64 treatment-emergent adverse events |
| TCZ 162 mg q1w or q2w | Number of Treatment-related Treatment-emergent Adverse Event | 32 treatment-emergent adverse events |
Secondary
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)
Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
Time frame: From baseline until Week 12
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 150 mg q4w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 33.0 ng/mL | Standard Error 4.65 |
| ALX-0061 150 mg q4w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 376 ng/mL | Standard Error 21.6 |
| ALX-0061 150 mg q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 460 ng/mL | Standard Error 19.9 |
| ALX-0061 150 mg q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 42.3 ng/mL | Standard Error 8.71 |
| ALX-0061 225 mg q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 30.9 ng/mL | Standard Error 3.72 |
| ALX-0061 225 mg q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 459 ng/mL | Standard Error 18.8 |
| TCZ 162 mg q1w or q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Baseline | 31.0 ng/mL | Standard Error 2.54 |
| TCZ 162 mg q1w or q2w | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) | Week 12 | 269 ng/mL | Standard Error 11.1 |
Secondary
Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12
Time frame: From baseline until Week 12
Population: PK Population, participants with data available
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ALX-0061 150 mg q4w | Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12 | 1.4 micrograms/milliliter | Standard Deviation 3.61 |
| ALX-0061 150 mg q2w | Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12 | 18.4 micrograms/milliliter | Standard Deviation 2.95 |
| ALX-0061 225 mg q2w | Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12 | 27.9 micrograms/milliliter | Standard Deviation 2.53 |