A Phase IIb Study for ALX-0061 Monotherapy in Subjects With Rheumatoid Arthritis

Ablynx, a Sanofi company251 enrolled

Overview

The primary objective of this study is: \- To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA). The secondary objectives of this study are: * To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development. * To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

251

Conditions

Rheumatoid Arthritis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of RA (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III. * Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use. * Subjects must not have received MTX for at least 4 weeks before first administration of the study drug. * Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline * Others as defined in the protocol Exclusion Criteria: * Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug. * Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase \[JAK\]-inhibitors) less than 6 months prior to screening. * Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs (including JAK inhibitors), for RA. * Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time. * Others as defined in the protocol.

Locations (83)

Investigator Site

Birmingham, Alabama, United States

Investigator Site

Hemet, California, United States

Investigator Site

La Palma, California, United States

Investigator site

Los Angeles, California, United States

Investigator Site

Los Angeles, California, United States

Investigator site

Outcomes

Primary Outcomes

Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12

ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.

Time frame: Week 12

Secondary Outcomes

Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12

ACR50/70 response is defined as: * 50/70% improvement in TJC (68 joints) relative to Week 0 AND * 50/70% improvement in SJC (66 joints) relative to Week 0 AND * 50/70% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level This endpoint was analyzed using NRI, i.e., subjects with missing response at Week 12 were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12

DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12

DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12

SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Low disease activity: 3.3 \< SDAI ≤ 11.0 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12

CDAI = TJC28 + SJC28 + VASPA + VASPHA Low disease activity: 2.8 \< CDAI ≤ 10 Subjects with low disease activity includes subjects who are in remission. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12

EULAR good response is defined as an improvement of \>1.2 in DAS28 (CRP) relative to baseline. This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Week 12

DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) Remission = DAS28(ESR) \< 2.6 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects in Remission Using SDAI at Week 12

SDAI = TJC28 + SJC28 + VASPA + VASPHA + CRP (mg/dL) Remission: SDAI ≤ 3.3 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects in Remission Using CDAI at Week 12

CDAI = TJC28 + SJC28 + VASPA + VASPHA Remission: CDAI ≤ 2.8 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12

Boolean remission: tender joint count (TJC)28 ≤ 1 and swollen joint count (SJC)28 ≤ 1 and VASPA (cm) ≤ 1 and CRP (mg/dL) ≤ 1 This endpoint was analyzed using NRI, i.e., subjects with missing response at the concerned visit were treated as non-responders.

Time frame: Week 12

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12

The HAQ-DI is a 20-question instrument which assesses the degree of difficulty the subject had in accomplishing tasks in 8 functional areas over the previous week. The 8 areas are: dressing and grooming, hygiene, arising, reach, eating, grip, walking, common daily activities. Within each area, subjects report the amount of difficulty they have in performing the specific items. There are 4 response options ranging from: 0 = No Difficulty, 1 = With Some Difficulty, 2 = With Much Difficulty, 3 = Unable to Do. The 8 areas are each given a single score equal to the maximum value of their component activities (0, 1, 2, or 3). The sum of the area scores is then divided by the number of areas answered to obtain the final HAQ score (rounded to the nearest value evenly divisible by 0.125). The final HAQ-DI score ranges from 0 to 3. A high score means a high degree of disability (=worse outcome). Missing values were imputed with the last non-missing observation.