A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis (PsA) Who Have an Inadequate Response to Methotrexate (MTX)

Study Overview
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Brief Summary
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This study is a Phase 2 randomized, double-blind, double-dummy, active- and placebo-controlled, parallel-group study designed to assess the safety, tolerability, efficacy, pharmacokinetics and immunogenicity of multiple doses of ABT-122 in participants with active PsA who are inadequately responding to MTX treatment.

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

Conditions
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Psoriatic 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: PsA diagnosis of at least 3 months duration prior to the date of first screening with ClASsification of Psoriatic ARthritis (CASPAR) confirmed diagnosis at Screening. Have active psoriasis defined by at least 1 psoriasis lesion >= 2 cm diameter in areas other than the axilla or groin. Have active arthritis defined by minimum disease activity criteria: >= 3 swollen joints (based on 66 joint counts) at Screening >= 3 tender joints (based on 68 joint counts) at Screening On a stable dose of methotrexate (MTX) defined as: Oral or parenteral treatment >= 3 months On a stable dose with an unchanged mode of application for at least 4 weeks prior to baseline Stable MTX dose of >= 10 mg/week and <= the upper limit of the applicable approved local label Can also be on stable doses of nonsteroidal anti-inflammatory drugs, sulfasalazine and/or hydroxychloroquine as long as they are also on methotrexate Exclusion Criteria: Up to 30% (approximately 66 subjects) with prior exposure to a TNF inhibitor may be enrolled if the TNF inhibitor was not discontinued due to lack of efficacy or safety concerns. Subjects must be washed out for at least 5 half-lives of these drugs prior to the Baseline visit. Subjects on prior adalimumab may not be enrolled in the study Prior exposure to other non-TNF inhibitor biological disease-modifying antirheumatic drugs (DMARDs) will be permitted if the subject is washed out at least 5 half-lives of these drugs prior to the baseline visit. Current treatment with traditional oral/intramuscular DMARDs, including conventional synthetic DMARDs (csDMARDs; except for concomitant treatment with sulfasalazine and/or hydroxychloroquine in addition to MTX). Oral DMARDs must be washed out for at least 5 half-lives of a drug apart from MTX prior to the Baseline visit. a. Subject could have been exposed to prior Janus kinase (JAK) or phosphodiesterase type 4 (PDE4) inhibitors so long as they have been off therapy for at least 5 half-lives. Stable prescribed dose of oral prednisone or prednisone equivalent > 10 mg/day within the 30 days of the Baseline visit. Intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks of the Baseline visit. 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, (or < 1200 cells/µL for subjects of African descent who are black) Aspartate aminotransferase or alanine aminotransferase > 1.5 x the upper limit of normal (ULN) or bilirubin >= 3 mg/dL Serum creatinine > 1.5 x the ULN Platelets < 100,000 cells/[mm^3] (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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab<br>Double-blind adalimumab 40 mg administered every other week (EOW) for 12 weeks | Biological: adalimumab<br> <br> * Other names: ABT-D2E7;|
| Placebo Comparator: Placebo<br>Double-blind placebo administered every week (EW) for 12 weeks | Biological: ABT-122<br> <br> * Other names: remtolumab;|
| Experimental: ABT-122 120 mg<br>Double-blind ABT-122 120 mg administered EW for 12 weeks | Biological: ABT-122<br> <br> * Other names: remtolumab;|
| Experimental: ABT-122 240 mg<br>Double-blind ABT-122 240 mg administered EW for 12 weeks | Biological: ABT-122<br> <br> * Other names: remtolumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology (ACR) 20 Response Rate at Week 12: ABT-122 Versus Placebo | Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant high sensitivity C-reactive protein [hsCRP]). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 Response Rate at Week 12: ABT-122 Versus Adalimumab | Percentage of participants with an ACR20 response, defined as at least 20% improvement (compared to baseline values) in tender and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP). Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. | Week 12 | 
| ACR50 Response Rate at Week 12 | Percentage of participants with an ACR50 response, defined as at least 50% improvement (compared to baseline values) in tender and swollen joint counts and at least 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. | Week 12 | 
| ACR70 Response Rate at Week 12 | Percentage of participants with an ACR70 response, defined as at least 70% improvement (compared to baseline values) in tender and swollen joint counts and at least 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function and acute phase reactant hsCRP. Estimates of the 95% confidence interval of the response rates for each treatment group were calculated using the Agresti-Coull method. | Week 12 | 
| ACRn at Week 12 | ACR measures percentage improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACRn is a continuous variable based on the ACR criteria. Improvement from baseline in a component of the ACR composite variable was computed as the difference between the baseline value and the value at a given post-baseline visit. A positive value for improvement from baseline for an individual component indicates lesser severity of disease. The 95% confidence interval for mean is constructed using T-statistic with significance level alpha=5%. | At Week 12 | 
| Change From Baseline in Disease Activity Score 28 (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, with higher scores indicating more disease activity. | Baseline, Week 12 | 
| Change From Baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) at Week 12 | PASDAS is a continuous compound disease activity state score determined by the combined values of tender or swollen joint counts, participant-reported outcome and hsCRP lab test. The PASDAS is unitless, with a typical score range between 0 and 10. Smaller values on PASDAS indicate a better condition; a negative change from baseline indicates improvement. | Baseline, Week 12 | 
| Change From Baseline in Psoriasis Target Lesion Score at Week 12 | Target lesion score for psoriasis in participants with psoriatic arthritis is calculated by adding the scores of plaque erythema, scaling and thickness. Scores range from 0 (no erythema or evidence of plaque thickness) to 10 (severe erythema and evidence of plaque thickness). | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Efficacy, Methotrexate