A Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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This study is a Phase 2 randomized, double-blind, double-dummy, parallel-group study designed to assess the safety, tolerability, efficacy, pharmacokinetics and immunogenicity of multiple doses of ABT 122 in subjects with active rheumatoid arthritis (RA) who are inadequately responding to methotrexate (MTX) treatment.

Official Title
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A Phase 2 Study to Investigate the Safety and Efficacy of ABT-122 Given With Methotrexate in Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: adalimumab
* Biological: ABT-122


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female, 18 years of age or older. Diagnosis of RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria (as defined in the definition of terms). Rheumatoid Arthritis (RA) diagnosis at least 3 months from the date of first Screening. Have active RA defined by minimum disease activity criteria: ≥ 6 Swollen joints (based on 66 joint counts) at screening and baseline visits. ≥ 6 Tender joints (based on 68 joint counts) at screening and baseline visits. hsCRP> ULN OR positive for both Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody levels at screening. Inadequate response to Methotrexate (MTX) treatment defined as oral or parenteral treatment ≥ 3 months with an unchanged mode of application and stable prescribed MTX dose for at least 4 weeks prior to baseline of ≥ 10mg/week and < the upper limit of the applicable approved local label. Subject can also be on stable doses of sulfasalazine and/or hydroxychloroquine, so long as they are also on methotrexate. Exclusion Criteria: Subject has previous exposure to Humira, other Tumor necrosis factor (TNF) inhibitors or other biological DMARDs. Current treatment with traditional oral Disease modifying antirheumatic drugs (DMARDs) (except for concomitant treatment with sulfasalazine and/or hydroxychloroquine in addition to MTX). Oral DMARDs must be washed out 5 times the mean terminal elimination half-life of a drug apart from MTX prior to Day 1. • Subject could have been exposed to prior Janus kinase (JAK) inhibitors so long as they have been off therapy for 5 half-lives. Stable prescribed dose of oral prednisone or prednisone equivalent > 10 mg/day within the 30 days of first dose of study drug. Intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks of first dose of study drug. Inhaled corticosteroids for stable medical conditions are allowed. Laboratory values of the following at the Screening Visit: Confirmed hemoglobin < 9 g/dL for males and < 8.5 g/dL for females, Absolute neutrophil count (ANC) < 1500 mm^3, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 × the upper limit of normal (ULN) or bilirubin ≥ 3 mg/dL, Serum creatinine > 1.5 × the ULN, Platelets < 100,000 cells/[mm3] (10^9/L), Clinically significant abnormal screening laboratory results as evaluated by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab 40 mg EOW<br>Adalimumab 40 mg every other week (EOW) for 11 weeks. | Biological: adalimumab<br>* adalimumab administered as subcutaneous injection every other week (EOW)<br>* Other names: Humira;|
| Experimental: ABT-122 60 mg EOW<br>ABT-122 60 mg every other week (EOW) for 11 weeks. | Biological: ABT-122<br>* ABT-122 administered as subcutaneous injection every other week (EOW)<br>|
| Experimental: ABT-122 120 mg EOW<br>ABT-122 120 mg every other week (EOW) for 11 weeks. | Biological: ABT-122<br>* ABT-122 administered as subcutaneous injection every other week (EOW)<br>|
| Experimental: ABT-122 120 mg EW<br>ABT-122 120 mg every week (EW) for 11 weeks. | Biological: ABT-122<br>* ABT-122 administered as subcutaneous injection every other week (EOW)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hsCRP). Last observation carried forward (LOCF) was used for missing data (only post-baseline values were carried forward). | Baseline (Day 1) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disease Activity Score 28 With High Sensitivity C-Reactive Protein (DAS28 [hsCRP]) | The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. A negative change from baseline represents improvement. n=the number of participants with evaluable data at each time point. LOCF was used (only post-baseline values were carried forward). | Baseline, Weeks 2, 4, 6, 8, and 12 | 
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12 | Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward). | Baseline (Day 1) and Week 12 | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 | Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hsCRP. LOCF was used (only post-baseline values were carried forward). | Baseline (Day 1) and Week 12 | 
| Percentage of Participants Achieving Low Disease Activity (LDA) or Clinical Remission (CR) Based on DAS28 (hsCRP) at Week 12 | The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. LDA is defined as a DAS28 (hsCRP) score from 2.6 to < 3.2 at Week 12. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward). | Week 12 | 
| Percentage of Participants Achieving CR Based on DAS28 (hsCRP) at Week 12 | The DAS28 (hsCRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hsCRP, and general health are included in the DAS28 (hsCRP) score. Scores range from 0 to 10: a score >5.1 indicates high disease activity, a score <3.2 indicates low disease activity, and a score <2.6 indicates clinical remission. CR is defined as a DAS28 (hsCRP) score < 2.6 at Week 12. LOCF was used (only post-baseline values were carried forward). | Week 12 | 
| Percentage of Participants Achieving LDA or CR Based on Clinical Disease Activity Index (CDAI) at Week 12 | The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. LDA is defined as a CDAI score from 2.8 to ≤ 10 at Week 12. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward). | Week 12 | 
| Percentage of Participants Achieving CR Based on Clinical Disease Activity Index (CDAI) at Week 12 | The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. CR is defined as a CDAI score ≤ 2.8 at Week 12. LOCF was used (only post-baseline values were carried forward). | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, Methotrexate, safety