A Study to Evaluate the Efficacy and Safety of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects

Phase 2b Study of ASP015K - A Double-Blind, Placebo-Controlled, Dose-Finding Study in Moderate to Severe Rheumatoid Arthritis Patients

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Placebo; Drug: peficitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
  • Chugoku, Japan
  • Hokkaido, Japan
  • Kansai, Japan
  • Kantou, Japan
  • Kyushu, Japan
  • Touhoku, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Oral	Drug: Placebo; oral
Experimental: ASP015K lowest dose; Oral	Drug: peficitinib; oral; Other Names: ASP015K
Experimental: ASP015K low dose; Oral	Drug: peficitinib; oral; Other Names: ASP015K
Experimental: ASP015K medium dose; Oral	Drug: peficitinib; oral; Other Names: ASP015K
Experimental: ASP015K high dose; Oral	Drug: peficitinib; oral; Other Names: ASP015K

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP)	Baseline and Week 12
Percentage of Subjects achieving ACR 50 response	Week 12
Percentage of Subjects achieving ACR 70 response	Week 12
Safety assessed by the incidence of adverse events, vital signs, 12-lead ECGs and clinical labo-tests	During 12-week treatment period and 4-week follow-up period

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): July 20, 2013
• Study Completion (Actual): July 20, 2013

Study Registration Dates

• First Submitted: July 23, 2012
• First Submitted That Met QC Criteria: July 23, 2012
• First Posted (Estimate): July 25, 2012

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; ASP015K
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Peficitinib
• Other Study ID Numbers: 015K-CL-RAJ1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes