Clinical trial NCT01554696: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: ASP015K
Rheumatoid Arthritis
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-03-15
Enrollment: 379
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response
timeFrame: Week 12
measure: Trough plasma concentration of ASP015K and metabolite(s)
timeFrame: up to 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Huntington Beach
country: United States
facility: The Talbert Group
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Santa Maria
country: United States
facility: Pacific Arthritis Center Medical Group
state: California
city: Colorado Springs
country: United States
facility: Arthritis Associates of Colorado Springs
state: Colorado
city: Orlando
country: United States
facility: Arthritis Associates
state: Florida
city: Morton Grove
country: United States
facility: Illinois Bone & Joint
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Asssociates
state: Illinois
city: Elizabethtown
country: United States
facility: Center for Arthritis and Osteoporosis
state: Kentucky
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Hickory
country: United States
facility: PMG Research
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clincal Research Center of Reading
state: Pennsylvania
city: Knoxville
country: United States
facility: Rheumatology Consultants, PLLC
state: Tennessee
city: Austin
country: United States
facility: Austin Rheumatology Research PA
state: Texas
city: Chesapeake
country: United States
facility: Center for Arthritis & Rheumatic Disease, P.C.
state: Virginia
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
city: Brussels
country: Belgium
facility: Hospital Erasme
city: Brussels
country: Belgium
facility: Moliere Hospital
city: Burgas
country: Bulgaria
facility: MHAT Burgas
city: Plovdiv
country: Bulgaria
facility: MHAT Plovdiv AD
city: Sofia
country: Bulgaria
facility: MHAT "Sv. Ivan Rilski"
city: Medellin
country: Colombia
facility: IPS Rodrigo Botero SAS
state: Antioquia
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatología del Caribe S.A.S
city: Bogota
country: Colombia
facility: Centro Integral De Reumatologia E Inmunologia
city: Bucaramanga
country: Colombia
facility: Medicity Sas
city: Bucaramanga
country: Colombia
facility: Servimed E.U.
city: Cali
country: Colombia
facility: Centro de medicina Interna Julian Coronel
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Uherske Hradiste
country: Czechia
facility: MEDICAL PLUS, s.r.o. or REVMACENTRUM UH, s.r.o.
city: Zlin
country: Czechia
facility: PV-MEDICAL s.r.o.
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft
city: Bekescsaba
country: Hungary
facility: Rethy Pal Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Revita Clinic Rheumatology
city: Debrecen
country: Hungary
facility: Kenezy Hospital Institute of Clinical Pharmacology
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion, SC Rheumatology
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde Gutierrez
city: Guadalajara
country: Mexico
facility: Dr Javier Orozco Alcala Private Doctor´s office
city: Mexico D.F.
country: Mexico
facility: Cliditer S.A. de C.V.Huerta S.I.
city: Morelia
country: Mexico
facility: Centro de Investigacion Clinica de Morelia, S.C.
city: Bialystok
country: Poland
facility: NZOZ Osteo-Medic sc A. Racewicz, J. Supronik
city: Bialystok
country: Poland
facility: Centrum Osteoporozy i Chorob KKostno-Stawowych Daniluk Clinical Research Centre
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr. 2 im. Dr. Jana Biziela
city: Krakow
country: Poland
facility: NZOZ Centrum Medyczne ProMiMed
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych REUMED sp. Zo.o
city: Warszawa
country: Poland
facility: ARS Rheumatica
city: Wraszawa
country: Poland
facility: Rheuma Medicus Zaktad Opieki Zdrowotnej Relle Brkolozka
Study officials:
affiliation: Astellas Pharma Global Development
name: Senior Medical Director Director
role: STUDY_DIRECTOR
References:
citation: 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.