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A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALX-0061
Placebo
Methotrexate
Sponsored by
Ablynx, a Sanofi company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo q2w + MTX

ALX-0061 75 mg q4w + MTX

ALX-0061 150 mg q4w + MTX

ALX-0061 150 mg q2w + MTX

ALX-0061 225 mg q2w + MTX

Arm Description

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 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 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 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 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response
Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity
Number of Treatment-emergent Adverse Events by Severity
Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events
Number of Treatment-related Treatment-emergent Adverse Events

Full Information

First Posted
November 27, 2014
Last Updated
August 6, 2019
Sponsor
Ablynx, a Sanofi company
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1. Study Identification

Unique Protocol Identification Number
NCT02309359
Brief Title
A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis
Official Title
A Phase IIb Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Range Finding Study of ALX-0061 Administered Subcutaneously in Combination With Methotrexate, in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ablynx, a Sanofi company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
345 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo q2w + MTX
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
ALX-0061 75 mg q4w + MTX
Arm Type
Experimental
Arm Description
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.
Arm Title
ALX-0061 150 mg q4w + MTX
Arm Type
Experimental
Arm Description
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.
Arm Title
ALX-0061 150 mg q2w + MTX
Arm Type
Experimental
Arm Description
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.
Arm Title
ALX-0061 225 mg q2w + MTX
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
ALX-0061
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Stable background dose of commercially available methotrexate (not provided by the Sponsor).
Primary Outcome Measure Information:
Title
Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12
Description
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
Secondary Outcome Measure Information:
Title
Number and Percentage of Subjects With ACR20 Response at Week 24
Description
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
Title
Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24
Description
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
Title
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
Description
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
Title
Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24
Description
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
Title
Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24
Description
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
Title
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24
Description
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
Title
Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
Description
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
Title
Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24
Description
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
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24
Description
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
Title
Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24
Description
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
Title
Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24
Description
Values below the limit of quantification are imputed with the lower limit of quantification (LLOQ).
Time Frame
from baseline till Week 24
Title
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)
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ablynx Clinical Department
Organizational Affiliation
Ablynx, a Sanofi company
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Facility Name
Investigator Site
City
Hemet
State/Province
California
ZIP/Postal Code
92543
Country
United States
Facility Name
Investigator Site
City
La Palma
State/Province
California
ZIP/Postal Code
90712
Country
United States
Facility Name
Investigator Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90017
Country
United States
Facility Name
Investigator site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
Facility Name
Investigator Site
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
Investigator Sites
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Investigator Site
City
Homestead
State/Province
Florida
ZIP/Postal Code
33030
Country
United States
Facility Name
Investigator Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Investigator Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Investigator Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Investigator Site
City
Stockbridge
State/Province
Georgia
ZIP/Postal Code
30281
Country
United States
Facility Name
Investigator Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66209
Country
United States
Facility Name
Investigator Site
City
Monroe
State/Province
Louisiana
ZIP/Postal Code
71203
Country
United States
Facility Name
Investigator Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Investigator Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Investigator Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Investigator Site
City
New York
State/Province
New York
ZIP/Postal Code
10018
Country
United States
Facility Name
Investigator Sie
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Investigator Site
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Investigator Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Investigator Site
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Investigator Site
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Investigator Site
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Investigator Site
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Investigator Site
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Investigator Site
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
Investigator Site
City
Plovdiv
ZIP/Postal Code
4001
Country
Bulgaria
Facility Name
Investigator Site 1
City
Ruse
ZIP/Postal Code
7000
Country
Bulgaria
Facility Name
Investigator Site 2
City
Ruse
ZIP/Postal Code
7000
Country
Bulgaria
Facility Name
Investigator Site
City
Sofia
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
Investigator Site
City
Sofia
ZIP/Postal Code
1612
Country
Bulgaria
Facility Name
Investigator Site
City
Varna
ZIP/Postal Code
9000
Country
Bulgaria
Facility Name
Investigator Site
City
Brno
ZIP/Postal Code
60200
Country
Czechia
Facility Name
Investigator Site
City
Olomouc
ZIP/Postal Code
77900
Country
Czechia
Facility Name
Investigator Site
City
Prague
ZIP/Postal Code
12850
Country
Czechia
Facility Name
Investigator Site
City
Prague
Country
Czechia
Facility Name
Investigator Site
City
Zlin
ZIP/Postal Code
76001
Country
Czechia
Facility Name
Investigator Site
City
Tbilisi
ZIP/Postal Code
0102
Country
Georgia
Facility Name
Investigator Site 1
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 2
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site
City
Tbilisi
ZIP/Postal Code
0160
Country
Georgia
Facility Name
Investigator Site
City
Tbilisi
ZIP/Postal Code
0179
Country
Georgia
Facility Name
Investigator Site
City
Bad Nauheim
ZIP/Postal Code
61231
Country
Germany
Facility Name
Investigator Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Investigator Site
City
Berlin
Country
Germany
Facility Name
Investigator Site
City
Cologne
ZIP/Postal Code
50973
Country
Germany
Facility Name
Investigator Site
City
Frankfurt
Country
Germany
Facility Name
Investigator Site
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Investigator Site
City
Baja
ZIP/Postal Code
6500
Country
Hungary
Facility Name
Investigator Site
City
Balatonfüred
ZIP/Postal Code
8230
Country
Hungary
Facility Name
Investigator Site
City
Budapest
ZIP/Postal Code
1038
Country
Hungary
Facility Name
Investigator Site
City
Békéscsaba
ZIP/Postal Code
5600
Country
Hungary
Facility Name
Investigator Site
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Investigator Site
City
Szikszó
ZIP/Postal Code
3800
Country
Hungary
Facility Name
Investigator Site
City
Székesfehérvar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Investigator Site
City
Veszprém
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Investigator Site
City
Culiacan
ZIP/Postal Code
80000
Country
Mexico
Facility Name
Investigator Site
City
Leon
ZIP/Postal Code
37000
Country
Mexico
Facility Name
Investigator Site
City
Merida
ZIP/Postal Code
97070
Country
Mexico
Facility Name
Investigator Site 1
City
Mexico City
ZIP/Postal Code
03100
Country
Mexico
Facility Name
Investigator Site 2
City
Mexico City
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Investigator Site
City
Monclova
ZIP/Postal Code
25714
Country
Mexico
Facility Name
Investigator Site
City
Monterey
ZIP/Postal Code
64000
Country
Mexico
Facility Name
Investigator Site
City
Monterey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Investigator Site
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Investigator Site 1
City
Skopje
ZIP/Postal Code
1000
Country
North Macedonia
Facility Name
Investigator Site 2
City
Skopje
ZIP/Postal Code
1000
Country
North Macedonia
Facility Name
Investigator Site
City
Bydgoszcz
ZIP/Postal Code
85168
Country
Poland
Facility Name
Investigator Site
City
Elblag
ZIP/Postal Code
82300
Country
Poland
Facility Name
Investigator Site
City
Elblag
Country
Poland
Facility Name
Investigator Site
City
Gdynia
ZIP/Postal Code
81338
Country
Poland
Facility Name
Investigator Site
City
Grodzisk Mazowiecki
ZIP/Postal Code
05825
Country
Poland
Facility Name
Investigator Site
City
Katowice
ZIP/Postal Code
40954
Country
Poland
Facility Name
Investigator Site
City
Lublin
ZIP/Postal Code
20582
Country
Poland
Facility Name
Investigator Site
City
Poznan
ZIP/Postal Code
60773
Country
Poland
Facility Name
Investigator Site
City
Sochaczew
ZIP/Postal Code
96500
Country
Poland
Facility Name
Investigator Site
City
Torun
ZIP/Postal Code
87100
Country
Poland
Facility Name
Investigator Site
City
Warszawa
ZIP/Postal Code
02653
Country
Poland
Facility Name
Investigator Site
City
Braila
ZIP/Postal Code
800578
Country
Romania
Facility Name
Investigator Site
City
Bucharest
ZIP/Postal Code
010976
Country
Romania
Facility Name
Investigator Site
City
Bucharest
ZIP/Postal Code
020475
Country
Romania
Facility Name
Investigator Site
City
Oradea
ZIP/Postal Code
410028
Country
Romania
Facility Name
Investigator Site
City
Targu Mures
ZIP/Postal Code
540142
Country
Romania
Facility Name
Investigator Site
City
Timisoara
ZIP/Postal Code
300057
Country
Romania
Facility Name
Investigator Site 1
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigator Site 2
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigator Site 3
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigator Site
City
Niska Banja
ZIP/Postal Code
18205
Country
Serbia
Facility Name
Investigator Site
City
Novi Sad
ZIP/Postal Code
21112
Country
Serbia
Facility Name
Investigator Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Investigator Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigator Site
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Investigator Site
City
Santiago de Compostela
ZIP/Postal Code
15702
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis

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