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
- Conditions
- Arthritis, Rheumatoid
- Interventions
- Registration Number
- NCT01554696
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 379
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ASP015K lowest dose methotrexate ASP015K lowest dose daily in addition to concomitant weekly oral methotrexate Placebo Placebo Placebo daily in addition to concomitant weekly oral methotrexate ASP015K high dose peficitinib ASP015K high dose daily in addition to concomitant weekly oral methotrexate ASP015K lowest dose peficitinib ASP015K lowest dose daily in addition to concomitant weekly oral methotrexate ASP015K low dose peficitinib ASP015K low dose daily in addition to concomitant weekly oral methotrexate ASP015K low dose methotrexate ASP015K low dose daily in addition to concomitant weekly oral methotrexate ASP015K medium dose peficitinib ASP015K medium dose daily in addition to concomitant weekly oral methotrexate ASP015K medium dose methotrexate ASP015K medium dose daily in addition to concomitant weekly oral methotrexate ASP015K high dose methotrexate ASP015K high dose daily in addition to concomitant weekly oral methotrexate Placebo methotrexate Placebo daily in addition to concomitant weekly oral methotrexate
- Primary Outcome Measures
Name Time Method Trough plasma concentration of ASP015K and metabolite(s) up to Week 12 Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response Week 12
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (49)
University of California San Diego
🇺🇸La Jolla, California, United States
The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
Hospital Erasme
🇧🇪Brussels, Belgium
Moliere Hospital
🇧🇪Brussels, Belgium
Centro Integral De Reumatologia E Inmunologia
🇨🇴Bogota, Colombia
IPS Rodrigo Botero SAS
🇨🇴Medellin, Antioquia, Colombia
Medicity Sas
🇨🇴Bucaramanga, Colombia
Servimed E.U.
🇨🇴Bucaramanga, Colombia
Centro de medicina Interna Julian Coronel
🇨🇴Cali, Colombia
DRC Gyogyszervizsgalo Kozpont Kft
🇭🇺Balatonfured, Hungary
Rethy Pal Korhaz es Rendelointezet
🇭🇺Bekescsaba, Hungary
Kenezy Hospital Institute of Clinical Pharmacology
🇭🇺Debrecen, Hungary
Dr Javier Orozco Alcala Private Doctor´s office
🇲🇽Guadalajara, Mexico
Cliditer S.A. de C.V.Huerta S.I.
🇲🇽Mexico D.F., Mexico
Centro de Investigacion Clinica de Morelia, S.C.
🇲🇽Morelia, Mexico
Centrum Osteoporozy i Chorob KKostno-Stawowych Daniluk Clinical Research Centre
🇵🇱Bialystok, Poland
NZOZ Centrum Medyczne ProMiMed
🇵🇱Krakow, Poland
Szpital Uniwersytecki nr. 2 im. Dr. Jana Biziela
🇵🇱Bydgoszcz, Poland
Achieve Clinical Research, LLC
🇺🇸Birmingham, Alabama, United States
Deerbrook Medical Asssociates
🇺🇸Vernon Hills, Illinois, United States
Clincal Research Center of Reading
🇺🇸Wyomissing, Pennsylvania, United States
Pacific Arthritis Center Medical Group
🇺🇸Santa Maria, California, United States
The Talbert Group
🇺🇸Huntington Beach, California, United States
Illinois Bone & Joint
🇺🇸Morton Grove, Illinois, United States
Desert Medical Advances
🇺🇸Palm Desert, California, United States
Arthritis Associates
🇺🇸Orlando, Florida, United States
Center for Arthritis and Osteoporosis
🇺🇸Elizabethtown, Kentucky, United States
PMG Research
🇺🇸Hickory, North Carolina, United States
Health Research of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Center for Arthritis & Rheumatic Disease, P.C.
🇺🇸Chesapeake, Virginia, United States
Austin Rheumatology Research PA
🇺🇸Austin, Texas, United States
Mountain State Clinical Research
🇺🇸Clarksburg, West Virginia, United States
Rheumatology Consultants, PLLC
🇺🇸Knoxville, Tennessee, United States
MHAT Burgas
🇧🇬Burgas, Bulgaria
MHAT Plovdiv AD
🇧🇬Plovdiv, Bulgaria
Centro Integral de Reumatología del Caribe S.A.S
🇨🇴Barranquilla, Colombia
MEDICAL PLUS, s.r.o. or REVMACENTRUM UH, s.r.o.
🇨🇿Uherske Hradiste, Czechia
PV-MEDICAL s.r.o.
🇨🇿Zlin, Czechia
Revita Clinic Rheumatology
🇭🇺Budapest, Hungary
Hospital Civil de Guadalajara Fray Antonio Alcalde Gutierrez
🇲🇽Guadalajara, Mexico
NZOZ Osteo-Medic sc A. Racewicz, J. Supronik
🇵🇱Bialystok, Poland
Zespol Poradni Specjalistycznych REUMED sp. Zo.o
🇵🇱Lublin, Poland
Morales Vargas Centro de Investigacion, SC Rheumatology
🇲🇽Leon, Guanajuato, Mexico
Arthritis Associates of Colorado Springs
🇺🇸Colorado Springs, Colorado, United States
MHAT "Sv. Ivan Rilski"
🇧🇬Sofia, Bulgaria
Revmatologicky ustav
🇨🇿Praha 2, Czechia
ARS Rheumatica
🇵🇱Warszawa, Poland
Rheuma Medicus Zaktad Opieki Zdrowotnej Relle Brkolozka
🇵🇱Wraszawa, Poland