Clinical trial NCT01649999: A Study to Evaluate the Efficacy and Safety of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects
Official title: Phase 2b Study of ASP015K - A Double-Blind, Placebo-Controlled, Dose-Finding Study in Moderate to Severe Rheumatoid Arthritis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: Rheumatoid Arthritis
ASP015K
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-07-25
Enrollment: 281
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the efficacy and safety of ASP015K monotherapy and to evaluate the dose-dependent response of ASP015K in moderate to severe Rheumatoid Arthritis (RA) subjects given ASP015K for 12 weeks.

Detailed description: This is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, dose-finding, monotherapy, multi-center study with once daily oral ASP015K or matching placebo in subjects with moderate to severe RA, with or without prior antirheumatic medication, and regardless of responsiveness to the medication.

The study is comprised of up to a 4-week Screening period, a 12-week Treatment period and a 4-week Follow-up period.

Subjects in each treatment group will take ASP015K or matching placebo orally, once daily, after breakfast for 12 weeks after the screening period.

Eligibility criteria: Inclusion Criteria:

* Subject has received a full explanation of the study drug and this study in advance, and written informed consent to participate in the study has been obtained from the subject himself/herself
* Outpatient has RA that was diagnosed according to the 1987 revised criteria of the ACR at least 6 months prior to screening
* At screening subject has active RA as evidenced by all of the following:

  * ≥ 6 tender/painful joints;
  * ≥ 6 swollen joints;
  * CRP of ≥ 0.5 mg/dL or ESR of ≥ 28 mm/h.C-Reactive Protein (CRP) of ≥ 0.8 mg/dL or Erythrocyte Sedimentation Rate (ESR) of ≥ 28 mm/hr
* Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA, Class I, II or, III at screening

Exclusion Criteria:

* Positive tuberculin (TB) test within 90 days of Screening
* Abnormal chest x-ray indicative of an acute or chronic infectious process or malignancy
* Receipt of live or live attenuated virus vaccination within 30 days prior to the first dose of study drug
* Hepatitis B virus or hepatitis C virus carrier or has a history of a positive test for human immunodeficiency virus (HIV) infection
* Any other autoimmune rheumatic disease, other than Sjogren's syndrome
* Previous history of clinically significant infections or illness (requiring hospitalization or requiring parenteral therapy) within 90 days of the Screening visit, or a history of any illness that would preclude participation in the study
* History of any malignancy, except for successfully treated basal or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix
* Does not meet specified washout criteria for the following RA medications: etanercept, certolizumab, adalimumab, golimumab, infliximab and tocilizumab, rituximab, abatacept, anakinra, methotrexate, sulfasalazine, hydroxychloroquine, gold, penicillamine or leflunomide
* Previous intolerance to Janus kinase (JAK) inhibitors
* Receipt of intra-articular or parenteral corticosteroid within 28 days prior to the first dose of study drug
* Receipt of plasma exchange therapy within 60 days prior to the start of study drug
* Receipt of any investigational agent within 30 days or 5 half-lives, whichever is longer, prior to first dose of study drug
* Receipt of medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to first dose of study drug
* History of heart failure, defined as New York Heart Association (NYHA) grade 3 or greater

Primary outcomes:
measure: Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Subjects achieving ACR 50 response
timeFrame: Week 12
measure: Percentage of Subjects achieving ACR 70 response
timeFrame: Week 12
measure: Change from baseline in Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP)
timeFrame: Baseline and Week 12
measure: Safety assessed by the incidence of adverse events, vital signs, 12-lead ECGs and clinical labo-tests
timeFrame: During 12-week treatment period and 4-week follow-up period
Other outcomes:
Locations:
city: Chubu
country: Japan
city: Chugoku
country: Japan
city: Hokkaido
country: Japan
city: Kansai
country: Japan
city: Kantou
country: Japan
city: Kyushu
country: Japan
city: Touhoku
country: Japan
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Toyoshima J, Kaibara A, Shibata M, Kaneko Y, Izutsu H, Nishimura T. Exposure-response modeling of peficitinib efficacy in patients with rheumatoid arthritis. Pharmacol Res Perspect. 2021 May;9(3):e00744. doi: 10.1002/prp2.744.
citation: Takeuchi T, Tanaka Y, Iwasaki M, Ishikura H, Saeki S, Kaneko Y. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study. Ann Rheum Dis. 2016 Jun;75(6):1057-64. doi: 10.1136/annrheumdis-2015-208279. Epub 2015 Dec 15.