Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of dose regimens of ALX-0061 administered subcutaneously (s.c.) in combination with methotrexate (MTX) to subjects with active rheumatoid arthritis (RA) despite MTX therapy, compared with placebo. To assess the effects of ALX-0061 on quality of life, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061, and to define the optimal dose regimen for ALX-0061, based on safety and efficacy, for further clinical development.
Detailed description
Subjects who completed the 24-week assessment period and achieved at least 20% improvement in swollen joint count (SJC) and/or tender joint count (TJC) at Week 24 of study ALX0061-C201 were invited to participate in an open-label extension (OLE) study ALX0061-C203 (NCT02518620), if the study was approved in their country and selection criteria were met.
Interventions
BIOLOGICALALX-0061
OTHERPlacebo
DRUGMethotrexate
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
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 for at least 6 months prior to screening, and American College of Rheumatology (ACR) functional class I-III * Subjects treated with and tolerating MTX * Active RA * Others as defined in the protocol
Exclusion criteria
* Have been treated with disease-modifying antirheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX. * Have received approved or investigational biological or targeted synthetic DMARD therapies for RA 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, 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 Achieving American College of Rheumatology (ACR) 20 Response 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 ACR50 Response at Weeks 12 and 24 | 24 weeks | ACR50 response is defined as: * 50% improvement in TJC (68 joints) relative to Week 0 AND * 50% improvement in SJC (66 joints) relative to Week 0 AND * 50% 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 the concerned visit were treated as non responders. |
| Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | 24 weeks | ACR70 response is defined as: * 70% improvement in TJC (68 joints) relative to Week 0 AND * 70% improvement in SJC (66 joints) relative to Week 0 AND * 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 the concerned visit were treated as non responders. |
| Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | 24 weeks | 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 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | SDAI = TJC28 + SJC28 + Patient's Global Assessment of Disease Activity (VASPA) + Physician's Global Assessment of Disease Activity (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 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | 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 Weeks 12 and 24 | 24 weeks | 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 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 ACR20 Response at Week 24 | 24 weeks | 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 This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 24 were treated as non responders. |
| Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | from baseline till Week 24 | 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. The lower the score the more disability. The higher the score the less disability. |
| Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | from baseline till Week 24 | 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. The lower the score the more disability. The higher the score the less disability. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | from baseline till Week 24 | 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. |
| Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | at Week 12 and Week 24 visits | ALX-0061 concentrations were only measured in samples of subjects randomized to any of the ALX-0061 treatment arms. Samples were taken predose at the concerned visits. |
| Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | from baseline till Week 24 | Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ). |
| Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation) | — |
| Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit | — |
| Number of Treatment-emergent Adverse Events by Severity | From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit | — |
| Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit | — |
| Number of Treatment-related Treatment-emergent Adverse Events | From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit | — |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | from baseline till Week 24 | 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 345 subjects were recruited at 63 sites located in Europe (46 sites; 259 subjects), Latin America (7 sites; 59 subjects) and North America (10 sites; 27 subjects). Consent was obtained from the first subject on 30 Jan 2015; the last subject completed the final visit on 8 Aug 2016.
Pre-assignment details
Of the 712 subjects screened, 367 were screen failures and 345 were randomly assigned to treatment (Intent-to-treat population). All subjects enrolled received study drug and were included in the safety population. All subjects who received at least one dose of ALX-0061 (i.e., 276 subjects) were included in the pharmacokinetic (PK) population.
Participants by arm
| Arm | Count |
|---|---|
| ALX-0061 75 mg q4w + MTX ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
ALX-0061
Placebo
Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor). | 69 |
| ALX-0061 150 mg q4w + MTX ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
ALX-0061
Placebo
Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor). | 70 |
| ALX-0061 150 mg q2w + MTX ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
ALX-0061
Placebo
Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor). | 68 |
| ALX-0061 225 mg q2w + MTX ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24.
The last study drug administration was at the Week 22 visit.
ALX-0061
Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor). | 69 |
| Placebo q2w + MTX Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
Placebo
Methotrexate: Stable background dose of commercially available methotrexate (not provided by the Sponsor). | 69 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 5 | 4 | 4 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 3 | 1 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 2 | 0 | 2 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 4 | 4 | 0 |
Baseline characteristics
| Characteristic | ALX-0061 75 mg q4w + MTX | ALX-0061 150 mg q4w + MTX | ALX-0061 150 mg q2w + MTX | ALX-0061 225 mg q2w + MTX | Placebo q2w + MTX | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 10 Participants | 11 Participants | 12 Participants | 14 Participants | 13 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 58 Participants | 56 Participants | 55 Participants | 56 Participants | 284 Participants |
| Age, Continuous | 53.3 years STANDARD_DEVIATION 10.35 | 52 years STANDARD_DEVIATION 13.16 | 51.9 years STANDARD_DEVIATION 11.93 | 52.3 years STANDARD_DEVIATION 13.36 | 52.8 years STANDARD_DEVIATION 11.92 | 52.4 years STANDARD_DEVIATION 12.14 |
| Sex: Female, Male Female | 58 Participants | 62 Participants | 59 Participants | 55 Participants | 55 Participants | 289 Participants |
| Sex: Female, Male Male | 11 Participants | 8 Participants | 9 Participants | 14 Participants | 14 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 69 | 0 / 70 | 0 / 68 | 0 / 69 | 0 / 69 |
| other Total, other adverse events | 29 / 69 | 34 / 70 | 27 / 68 | 38 / 69 | 17 / 69 |
| serious Total, serious adverse events | 5 / 69 | 5 / 70 | 0 / 68 | 2 / 69 | 4 / 69 |
Outcome results
Primary
Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response 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 75 mg q4w + MTX | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | 52 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | 57 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | 53 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | 50 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12 | 43 Participants |
Comparison: The null hypothesis of this test was that there is no difference in the percentage of subjects achieving ACR20 response between the treatment groups and the alternative hypothesis was that the percentage of subjects achieving ACR20 response increases with increasing dose level.p-value: 0.172Cochran-Armitage trend test
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24
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 till Week 24
Population: Intent-to-treat population; Number Analyzed reflect the number of non-missing, non-imputed observations at that specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 24 | 12.446 score on a scale | Standard Error 1.5687 |
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 12 | 11.014 score on a scale | Standard Error 1.3593 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 12 | 8.63 score on a scale | Standard Error 1.0465 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 24 | 10.439 score on a scale | Standard Error 1.2157 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 12 | 10.884 score on a scale | Standard Error 1.5424 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 24 | 13.374 score on a scale | Standard Error 1.5621 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 24 | 12.381 score on a scale | Standard Error 1.5193 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 12 | 9.389 score on a scale | Standard Error 1.3706 |
| Placebo q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 24 | 6.712 score on a scale | Standard Error 1.4651 |
| Placebo q2w + MTX | Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24 | Week 12 | 6.381 score on a scale | Standard Error 1.2026 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24
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 till Week 24
Population: Intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 12 | -0.696 score on a scale | Standard Error 0.0857 |
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 24 | -0.82 score on a scale | Standard Error 0.0913 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 12 | -0.619 score on a scale | Standard Error 0.0657 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 24 | -0.665 score on a scale | Standard Error 0.0682 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 12 | -0.771 score on a scale | Standard Error 0.0763 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 24 | -0.876 score on a scale | Standard Error 0.0802 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 12 | -0.615 score on a scale | Standard Error 0.0858 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 24 | -0.772 score on a scale | Standard Error 0.0926 |
| Placebo q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 24 | -0.662 score on a scale | Standard Error 0.0798 |
| Placebo q2w + MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24 | Week 12 | -0.613 score on a scale | Standard Error 0.0718 |
Secondary
Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
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. The lower the score the more disability. The higher the score the less disability.
Time frame: from baseline till Week 24
Population: Intent-to-treat population; Number Analyzed reflect the number of non-missing, non-imputed observations at that specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 9.857 score on a scale | Standard Error 1.5326 |
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 9.096 score on a scale | Standard Error 1.4966 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 7.962 score on a scale | Standard Error 1.3932 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 7.249 score on a scale | Standard Error 1.1237 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 11.739 score on a scale | Standard Error 1.4159 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 9.749 score on a scale | Standard Error 1.4177 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 5.686 score on a scale | Standard Error 1.6485 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 8.981 score on a scale | Standard Error 1.6876 |
| Placebo q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 5.569 score on a scale | Standard Error 1.6467 |
| Placebo q2w + MTX | Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 6.198 score on a scale | Standard Error 1.696 |
Secondary
Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
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. The lower the score the more disability. The higher the score the less disability.
Time frame: from baseline till Week 24
Population: Intent-to-treat population; Number Analyzed reflect the number of non-missing, non-imputed observations at that specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 7.372 score on a scale | Standard Error 0.9136 |
| ALX-0061 75 mg q4w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 10.412 score on a scale | Standard Error 1.0642 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 7.100 score on a scale | Standard Error 0.7477 |
| ALX-0061 150 mg q4w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 8.725 score on a scale | Standard Error 0.9194 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 6.534 score on a scale | Standard Error 0.8878 |
| ALX-0061 150 mg q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 8.835 score on a scale | Standard Error 1.009 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 10.762 score on a scale | Standard Error 1.1497 |
| ALX-0061 225 mg q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 7.778 score on a scale | Standard Error 0.994 |
| Placebo q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 24 | 7.255 score on a scale | Standard Error 0.9483 |
| Placebo q2w + MTX | Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24 | Week 12 | 5.413 score on a scale | Standard Error 0.7813 |
Secondary
Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24
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 non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 24 | 6 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 12 | 0 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 24 | 9 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 12 | 5 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 24 | 6 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 12 | 2 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 12 | 4 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 24 | 13 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 24 | 6 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24 | Week 12 | 3 Participants |
Secondary
Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 24 | 10 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 12 | 3 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 12 | 7 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 24 | 13 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 12 | 4 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 24 | 8 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 12 | 5 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 24 | 13 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 24 | 7 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24 | Week 12 | 3 Participants |
Secondary
Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 12 | 3 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 24 | 17 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 24 | 26 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 12 | 26 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 12 | 15 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 24 | 23 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 24 | 37 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 12 | 21 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 12 | 6 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24 | Week 24 | 8 Participants |
Secondary
Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 12 | 2 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 24 | 7 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 24 | 13 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 12 | 8 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 12 | 6 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 24 | 10 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 24 | 14 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 12 | 5 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 24 | 6 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24 | Week 12 | 3 Participants |
Secondary
Number and Percentage of Subjects With ACR20 Response at Week 24
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 This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 24 were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With ACR20 Response at Week 24 | 51 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With ACR20 Response at Week 24 | 55 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With ACR20 Response at Week 24 | 49 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With ACR20 Response at Week 24 | 52 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With ACR20 Response at Week 24 | 51 Participants |
Secondary
Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24
ACR50 response is defined as: * 50% improvement in TJC (68 joints) relative to Week 0 AND * 50% improvement in SJC (66 joints) relative to Week 0 AND * 50% 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 the concerned visit were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 12 | 20 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 24 | 33 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 12 | 31 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 24 | 39 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 12 | 28 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 24 | 37 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 24 | 42 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 12 | 31 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 12 | 19 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24 | Week 24 | 27 Participants |
Secondary
Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24
ACR70 response is defined as: * 70% improvement in TJC (68 joints) relative to Week 0 AND * 70% improvement in SJC (66 joints) relative to Week 0 AND * 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 the concerned visit were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 12 | 10 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 24 | 16 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 12 | 15 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 24 | 23 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 12 | 13 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 24 | 15 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 24 | 31 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 12 | 12 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 12 | 6 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24 | Week 24 | 12 Participants |
Secondary
Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 12 | 15 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 24 | 26 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 12 | 36 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 24 | 39 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 12 | 30 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 24 | 39 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 24 | 47 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 12 | 39 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 12 | 15 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24 | Week 24 | 19 Participants |
Secondary
Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 12 | 22 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 24 | 29 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 12 | 31 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 24 | 33 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 24 | 29 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 12 | 26 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 12 | 23 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 24 | 43 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 12 | 17 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24 | Week 24 | 23 Participants |
Secondary
Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24
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: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 12 | 13 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 24 | 24 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 12 | 36 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 24 | 38 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 12 | 29 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 24 | 33 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 24 | 46 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 12 | 33 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 12 | 11 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24 | Week 24 | 13 Participants |
Secondary
Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24
SDAI = TJC28 + SJC28 + Patient's Global Assessment of Disease Activity (VASPA) + Physician's Global Assessment of Disease Activity (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 NRI, i.e., subjects with missing response at the concerned visit were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 12 | 49 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 24 | 29 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 12 | 34 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 24 | 34 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 12 | 29 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 24 | 35 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 24 | 46 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 12 | 25 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 12 | 17 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24 | Week 24 | 22 Participants |
Secondary
Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24
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 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non responders.
Time frame: 24 weeks
Population: Intent-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 12 | 16 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 24 | 26 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 12 | 37 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 24 | 40 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 12 | 32 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 24 | 41 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 24 | 48 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 12 | 40 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 12 | 16 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24 | Week 24 | 20 Participants |
Secondary
Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity
Time frame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Mild | 21 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Severe | 6 Participants |
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Moderate | 15 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Moderate | 12 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Mild | 28 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Severe | 4 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Moderate | 19 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Mild | 23 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Severe | 2 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Mild | 20 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Severe | 4 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Moderate | 20 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Moderate | 14 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Mild | 20 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity | Severe | 2 Participants |
Secondary
Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events
Time frame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | 26 Participants |
| ALX-0061 150 mg q4w + MTX | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | 25 Participants |
| ALX-0061 150 mg q2w + MTX | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | 26 Participants |
| ALX-0061 225 mg q2w + MTX | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | 25 Participants |
| Placebo q2w + MTX | Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events | 18 Participants |
Secondary
Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
Time frame: from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 9 Participants |
| ALX-0061 150 mg q4w + MTX | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 16 Participants |
| ALX-0061 150 mg q2w + MTX | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 31 Participants |
| ALX-0061 225 mg q2w + MTX | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 33 Participants |
| Placebo q2w + MTX | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 13 Participants |
| ALX-0061 Total | Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response | 89 Participants |
Secondary
Number of Treatment-emergent Adverse Events by Severity
Time frame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Severe | 6 Adverse events |
| ALX-0061 75 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Mild | 66 Adverse events |
| ALX-0061 75 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Moderate | 34 Adverse events |
| ALX-0061 150 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Severe | 5 Adverse events |
| ALX-0061 150 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Moderate | 24 Adverse events |
| ALX-0061 150 mg q4w + MTX | Number of Treatment-emergent Adverse Events by Severity | Mild | 78 Adverse events |
| ALX-0061 150 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Mild | 66 Adverse events |
| ALX-0061 150 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Moderate | 26 Adverse events |
| ALX-0061 150 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Severe | 4 Adverse events |
| ALX-0061 225 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Moderate | 40 Adverse events |
| ALX-0061 225 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Mild | 56 Adverse events |
| ALX-0061 225 mg q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Severe | 5 Adverse events |
| Placebo q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Severe | 2 Adverse events |
| Placebo q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Mild | 49 Adverse events |
| Placebo q2w + MTX | Number of Treatment-emergent Adverse Events by Severity | Moderate | 22 Adverse events |
Secondary
Number of Treatment-related Treatment-emergent Adverse Events
Time frame: From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALX-0061 75 mg q4w + MTX | Number of Treatment-related Treatment-emergent Adverse Events | 55 Adverse events |
| ALX-0061 150 mg q4w + MTX | Number of Treatment-related Treatment-emergent Adverse Events | 52 Adverse events |
| ALX-0061 150 mg q2w + MTX | Number of Treatment-related Treatment-emergent Adverse Events | 46 Adverse events |
| ALX-0061 225 mg q2w + MTX | Number of Treatment-related Treatment-emergent Adverse Events | 47 Adverse events |
| Placebo q2w + MTX | Number of Treatment-related Treatment-emergent Adverse Events | 21 Adverse events |
Secondary
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24
Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
Time frame: from baseline till Week 24
Population: Safety Population; Number Analyzed reflect the number of subjects with data available at that specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 24 | 150 ng/mL | Standard Error 12.9 |
| ALX-0061 75 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 12 | 166 ng/mL | Standard Error 16.7 |
| ALX-0061 75 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Baseline | 26.9 ng/mL | Standard Error 0.995 |
| ALX-0061 150 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 24 | 422 ng/mL | Standard Error 17.8 |
| ALX-0061 150 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Baseline | 29.2 ng/mL | Standard Error 1.04 |
| ALX-0061 150 mg q4w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 12 | 420 ng/mL | Standard Error 21 |
| ALX-0061 150 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Baseline | 27.7 ng/mL | Standard Error 0.78 |
| ALX-0061 150 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 24 | 484 ng/mL | Standard Error 16.3 |
| ALX-0061 150 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 12 | 519 ng/mL | Standard Error 16.8 |
| ALX-0061 225 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 24 | 487 ng/mL | Standard Error 14.3 |
| ALX-0061 225 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Baseline | 28.9 ng/mL | Standard Error 1.05 |
| ALX-0061 225 mg q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 12 | 488 ng/mL | Standard Error 16.8 |
| Placebo q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 12 | 52.9 ng/mL | Standard Error 14.1 |
| Placebo q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Baseline | 28.9 ng/mL | Standard Error 1.1 |
| Placebo q2w + MTX | Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24 | Week 24 | 35.4 ng/mL | Standard Error 6.6 |
Secondary
Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24
ALX-0061 concentrations were only measured in samples of subjects randomized to any of the ALX-0061 treatment arms. Samples were taken predose at the concerned visits.
Time frame: at Week 12 and Week 24 visits
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ALX-0061 75 mg q4w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 12 | 0.163 micrograms/milliliter | Standard Deviation 3.7 |
| ALX-0061 75 mg q4w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 24 | 0.122 micrograms/milliliter | Standard Deviation 2.56 |
| ALX-0061 150 mg q4w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 24 | 1.64 micrograms/milliliter | Standard Deviation 3.11 |
| ALX-0061 150 mg q4w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 12 | 1.79 micrograms/milliliter | Standard Deviation 3.08 |
| ALX-0061 150 mg q2w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 24 | 20.9 micrograms/milliliter | Standard Deviation 1.5 |
| ALX-0061 150 mg q2w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 12 | 19.9 micrograms/milliliter | Standard Deviation 1.56 |
| ALX-0061 225 mg q2w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 12 | 32.1 micrograms/milliliter | Standard Deviation 1.43 |
| ALX-0061 225 mg q2w + MTX | Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24 | Week 24 | 35.2 micrograms/milliliter | Standard Deviation 1.37 |