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)

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Biological: adalimumab; Biological: ABT-122

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. >= 3 swollen joints (based on 66 joint counts) at Screening
  2. >= 3 tender joints (based on 68 joint counts) at Screening

• On a stable dose of methotrexate (MTX) defined as:

  1. Oral or parenteral treatment >= 3 months
  2. On a stable dose with an unchanged mode of application for at least 4 weeks prior to baseline
  3. Stable MTX dose of >= 10 mg/week and <= the upper limit of the applicable approved local label
  4. 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:

  1. Confirmed hemoglobin < 9 g/dL for males and < 8.5 g/dL for females
  2. Absolute neutrophil count (ANC) < 1500 mm^3, (or < 1200 cells/µL for subjects of African descent who are black)
  3. Aspartate aminotransferase or alanine aminotransferase > 1.5 x the upper limit of normal (ULN) or bilirubin >= 3 mg/dL
  4. Serum creatinine > 1.5 x the ULN
  5. Platelets < 100,000 cells/[mm^3] (10^9/L),
  6. Clinically significant abnormal screening laboratory results as evaluated by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Paul Peloso, MD, AbbVie

Publications and helpful links

General Publications

• Khatri A, Klunder B, Peloso PM, Othman AA. Exposure-response analyses demonstrate no evidence of interleukin 17A contribution to efficacy of ABT-122 in rheumatoid or psoriatic arthritis. Rheumatology (Oxford). 2019 Feb 1;58(2):352-360. doi: 10.1093/rheumatology/key312.
• Mease PJ, Genovese MC, Weinblatt ME, Peloso PM, Chen K, Othman AA, Li Y, Mansikka HT, Khatri A, Wishart N, Liu J. Phase II Study of ABT-122, a Tumor Necrosis Factor- and Interleukin-17A-Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2018 Nov;70(11):1778-1789. doi: 10.1002/art.40579.

Helpful Links

• Humira Prescribing info

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2015
• Primary Completion (Actual): July 4, 2016
• Study Completion (Actual): July 4, 2016

Study Registration Dates

• First Submitted: January 23, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Methotrexate; Efficacy
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M14-197; 2014-003558-15 (EudraCT Number)