A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects Who Have Had an Inadequate Response to Methotrexate

A Phase 2b, Randomized, Double-blind, Parallel-group, Placebo Controlled, Dose-finding, Multi-center Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis in Patients Who Have Had an Inadequate Response to Methotrexate

The purpose of this study is to evaluate the safety and efficacy of ASP015K in moderate to severe rheumatoid arthritis subjects who are methotrexate-inadequate responders (MTX-IR).

Study Overview

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

Detailed Description

Subjects in each treatment group will continue to take their concomitant oral weekly dose of methotrexate (MTX) in addition to daily ASP015K or matching placebo, taken orally with food, daily for 12 weeks after randomization.

• Study Type: Interventional
• Enrollment (Actual): 379
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Hospital Erasme
  • Brussels, Belgium, 1190
    • Moliere Hospital
• Bulgaria
  • Burgas, Bulgaria, 8000
    • MHAT Burgas
  • Plovdiv, Bulgaria, 4003
    • MHAT Plovdiv AD
  • Sofia, Bulgaria, 1612
    • MHAT "Sv. Ivan Rilski"
• Colombia
  • Barranquilla, Colombia
    • Centro Integral de Reumatologia del Caribe S.A.S
  • Bogota, Colombia
    • Centro Integral de Reumatologia e Inmunologia
  • Bucaramanga, Colombia
    • Servimed E.U.
  • Bucaramanga, Colombia
    • Medicity SAS
  • Cali, Colombia
    • Centro de medicina Interna Julian Coronel
  • Antioquia
    • Medellin, Antioquia, Colombia, 5001000
      • IPS Rodrigo Botero SAS
• Czechia
  • Praha 2, Czechia, 128 50
    • Revmatologicky Ustav
  • Uherske Hradiste, Czechia, 68601
    • MEDICAL PLUS, s.r.o. or REVMACENTRUM UH, s.r.o.
  • Zlin, Czechia, 760 01
    • PV-Medical s.r.o.
• Hungary
  • Balatonfured, Hungary, H-8230
    • DRC Gyogyszervizsgalo Kozpont Kft
  • Bekescsaba, Hungary, 5600
    • Rethy Pal Korhaz es Rendelointezet
  • Budapest, Hungary, 1027
    • Revita Clinic Rheumatology
  • Debrecen, Hungary, H-4043
    • Kenezy Hospital Institute of Clinical Pharmacology
• Mexico
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde Gutierrez
  • Guadalajara, Mexico, 44650
    • Dr Javier Orozco Alcala Private Doctor´s office
  • Mexico D.F., Mexico, 6700
    • Cliditer S.A. de C.V.Huerta S.I.
  • Morelia, Mexico, 58070
    • Centro de Investigacion Clinica de Morelia, S.C.
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
      • Morales Vargas Centro de Investigacion, SC Rheumatology
• Poland
  • Bialystok, Poland, 15-351
    • NZOZ Osteo-Medic sc A. Racewicz, J. Supronik
  • Bialystok, Poland, 15-461
    • Centrum Osteoporozy i Chorob KKostno-Stawowych Daniluk Clinical Research Centre
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr. 2 im. Dr. Jana Biziela
  • Krakow, Poland, 31-637
    • NZOZ Centrum Medyczne ProMiMed
  • Lublin, Poland, 20-582
    • Zespol Poradni Specjalistycznych REUMED sp. Zo.o
  • Warszawa, Poland, 02-653
    • ARS Rheumatica
  • Wraszawa, Poland, 02-118
    • Rheuma Medicus Zaktad Opieki Zdrowotnej Relle Brkolozka
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • California
    • Huntington Beach, California, United States, 92646
      • The Talbert Group
    • La Jolla, California, United States, 92093-0943
      • University of California San Diego
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
    • Santa Maria, California, United States, 93454
      • Pacific Arthritis Center Medical Group
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Arthritis Associates of Colorado Springs
  • Florida
    • Orlando, Florida, United States, 32804
      • Arthritis Associates
  • Illinois
    • Morton Grove, Illinois, United States, 60053
      • Illinois Bone & Joint
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Asssociates
  • Kentucky
    • Elizabethtown, Kentucky, United States, 42701
      • Center for Arthritis and Osteoporosis
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • PMG Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clincal Research Center of Reading
  • Tennessee
    • Knoxville, Tennessee, United States, 37909-1907
      • Rheumatology Consultants, PLLC
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Rheumatology Research PA
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Center for Arthritis & Rheumatic Disease, P.C.
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has rheumatoid arthritis (RA) diagnosed according to the 1987 revised ACR criteria for at least 6 months prior to Screening
• Subject has been treated with oral methotrexate (MTX) for a minimum of 90 days and at a stable dose for 28 days prior to the first dose of study drug
• ≥6 tender/painful joints; ≥6 swollen joints
• Subject meets the ACR 1991 Revised Criteria for Global Functional Status in RA Class I, II or III at Screening and Baseline
• Subject's other medication taken for treatment of RA must be stable for at least 28 days prior to start of the study
• Male and female subjects must be willing to comply with contraception requirements as well as restrictions regarding egg and sperm donation
• Female subject must not be breastfeeding at Screening or during the study period, and for 60 days after the final study drug administration
• Subject agrees not to participate in another interventional study while on treatment

Exclusion Criteria:

• Positive Mycobacterium tuberculosis (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
• Known history of positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody or history of a positive test for human immunodeficiency virus (HIV) infection
• History of 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 Baseline 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: gold, azathioprine, minocycline, penicillamine, etanercept, certolizumab, adalimumab, golimumab, infliximab, cyclophosphamide, and leflunomide
• Subject has previously used a non anti-TNF biologic disease-modifying antirheumatic drug (DMARD) (e.g., anakinra, abatacept, rituximab, tocilizumab)
• 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 or is currently taking > 30 mg oral morphine (or narcotic equivalent) per day
• Absolute lymphocyte count (ALC) < 750/mm3
• 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
• History of long QT syndrome or prolonged QT interval
• Any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or infectious disease, or any ongoing illness which would make the subject unsuitable for the study. This includes stomatitis, gastrointestinal ulcers, or any other condition that would preclude continued treatment with methotrexate
• Subject has any condition possibly affecting oral absorption (e.g., gastrectomy, other malabsorption syndromes, or clinically significant diabetic gastroenteropathy)

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
Experimental: ASP015K lowest dose; ASP015K lowest dose daily in addition to concomitant weekly oral methotrexate	Drug: peficitinib; oral; Other Names: ASP015K; Drug: methotrexate; oral
Experimental: ASP015K low dose; ASP015K low dose daily in addition to concomitant weekly oral methotrexate	Drug: peficitinib; oral; Other Names: ASP015K; Drug: methotrexate; oral
Experimental: ASP015K medium dose; ASP015K medium dose daily in addition to concomitant weekly oral methotrexate	Drug: peficitinib; oral; Other Names: ASP015K; Drug: methotrexate; oral
Experimental: ASP015K high dose; ASP015K high dose daily in addition to concomitant weekly oral methotrexate	Drug: peficitinib; oral; Other Names: ASP015K; Drug: methotrexate; oral
Placebo Comparator: Placebo; Placebo daily in addition to concomitant weekly oral methotrexate	Drug: Placebo; oral; Drug: methotrexate; oral

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
Trough plasma concentration of ASP015K and metabolite(s)	up to Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects achieving ACR 50 response	Week 12
Percentage of subjects achieving ACR 70 response	Week 12
Change from baseline in Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP)	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Senior Medical Director Director, Astellas Pharma Global Development

Publications and helpful links

General Publications

• Kivitz AJ, Gutierrez-Urena SR, Poiley J, Genovese MC, Kristy R, Shay K, Wang X, Garg JP, Zubrzycka-Sienkiewicz A. Peficitinib, a JAK Inhibitor, in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2017 Apr;69(4):709-719. doi: 10.1002/art.39955.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2012
• Primary Completion (Actual): February 11, 2014
• Study Completion (Actual): February 11, 2014

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 13, 2012
• First Posted (Estimate): March 15, 2012

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Peficitinib
• Other Study ID Numbers: 015K-CL-RA21; 2011-006018-15 (EudraCT Number)

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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)