Clinical trial NCT02141997: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: efficacy
Methotrexate
safety
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2014-05-20
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Adult male or female, 18 years of age or older.
2. 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).
3. Rheumatoid Arthritis (RA) diagnosis at least 3 months from the date of first Screening.
4. 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.
5. 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:

1. Subject has previous exposure to Humira, other Tumor necrosis factor (TNF) inhibitors or other biological DMARDs.
2. 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.
3. Stable prescribed dose of oral prednisone or prednisone equivalent \> 10 mg/day within the 30 days of first dose of study drug.
4. 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.
5. 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.

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
timeFrame: Baseline (Day 1) and Week 12
Secondary outcomes:
measure: Change in Disease Activity Score 28 With High Sensitivity C-Reactive Protein (DAS28 [hsCRP])
timeFrame: Baseline, Weeks 2, 4, 6, 8, and 12
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) or Clinical Remission (CR) Based on DAS28 (hsCRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving CR Based on DAS28 (hsCRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving LDA or CR Based on Clinical Disease Activity Index (CDAI) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving CR Based on Clinical Disease Activity Index (CDAI) at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Heikki Mansikka, MD
role: STUDY_DIRECTOR
References:
citation: Genovese MC, Weinblatt ME, Aelion JA, Mansikka HT, Peloso PM, Chen K, Li Y, Othman AA, Khatri A, Khan NS, Padley RJ. ABT-122, a Bispecific Dual Variable Domain Immunoglobulin Targeting Tumor Necrosis Factor and Interleukin-17A, in Patients With Rheumatoid Arthritis With an Inadequate Response to Methotrexate: A Randomized, Double-Blind Study. Arthritis Rheumatol. 2018 Nov;70(11):1710-1720. doi: 10.1002/art.40580. Epub 2018 Oct 10.