Efficacy and Safety Study of ABP 501 Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of ABP 501 against adalimumab (HUMIRA®) in adults with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX).

Official Title
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A Randomized, Double-blind, Phase 3 Study of ABP 501 Efficacy and Safety Compared to Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Biological: ABP 501
* Biological: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥ 18 and ≤ 80 years old Subjects must be diagnosed with rheumatoid arthritis for at least 3 months before baseline Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline Subjects must be taking MTX for ≥ 12 consecutive weeks and on a stable dose of 7.5 to 25 mg/week for > 8 weeks prior to receiving the study drug and be willing to remain on stable dose throughout the study Subject has no known history of active tuberculosis Exclusion Criteria: Class IV RA, Felty's syndrome or history of prosthetic or native joint infection Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome Prior use of 2 or more biologic therapies for RA Previous receipt of HUMIRA® (adalimumab) or a biosimilar of adalimumab Ongoing use of prohibited treatments Other Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP 501<br>Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22. | Biological: ABP 501<br>* Solution for subcutaneous injection in pre-filled syringe<br>* Other names: Adalimumab-atto;|
| Active Comparator: Adalimumab<br>Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22. | Biological: Adalimumab<br>* Solution for subcutaneous injection in pre-filled syringe<br>* Other names: HUMIRA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 24 | A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein level. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Disease Activity Score 28-C-reactive Protein (DAS28-CRP) | The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: The number of swollen and tender joints assessed using the 28-joint count; C-reactive protein (CRP) level Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable). The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity. A repeated measures analysis with the DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and the baseline DAS28-CRP measurement as predictors in the model was performed. | Baseline and weeks 2, 4, 8, 12, 18, and 24 | 
| Percentage of Participants With an ACR20 Response at Week 2 and Week 8 | A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein level. | Baseline, week 2 and week 8 | 
| Percentage of Participants With an ACR50 Response at Week 24 | A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein level. | Baseline and week 24 | 
| Percentage of Participants With an ACR70 Response at Week 24 | A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a likert scale from 0 to 10); Physician's global assessment of disease activity (measured on a likert scale from 0 to 10); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-Reactive Protein level. | Baseline and Week 24 | 
| Number of Participants With Adverse Events | Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product was yes. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: fatal life threatening (places the subject at immediate risk of death) requires inpatient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. | From the time of first treatment up to 28 days following the last dose of study treatment; 26 weeks. | 
| Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab | Two validated assays were used to detect the presence of anti-drug antibodies. Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against ABP 501 and adalimumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501 or adalimumab (Neutralizing Antibody Assay). Developing antibody incidence is defined as a negative or no antibody result at baseline and a positive antibody result at a post-baseline time point. | Up to week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Rheumatoid