Clinical trial NCT01565655: A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis
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 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: 2012-03-29
Enrollment: 289
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 (RA) subjects

Detailed description: Subjects will take ASP015K or matching placebo orally with food for 12 weeks after randomization. Potential subjects who have previously used disease-modifying antirheumatic drugs (DMARDs) and/or biologic agents may be eligible to participate after completing a washout period. Subjects who complete the 12-week dosing period in this study may be eligible to participate in a long-term, open-label Extension Study.

Eligibility criteria: Inclusion Criteria:

* ≥ 6 tender/painful joints; ≥ 6 swollen joints
* 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 Global Functional Status in RA Class I, II or III at Screening and Baseline
* Use of non-steroidal anti-inflammatory drugs \[NSAIDs\], cyclooxygenase-2 (COX-2) inhibitors, or oral corticosteroids for the 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
* 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
* 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
* 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 (6 time points)
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: 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: Palo Alto
country: United States
facility: Stanford University School of Medicine
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: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Orlando
country: United States
facility: Arthritis Associates
state: Florida
city: Morton Grove
country: United States
facility: Illinois Bone & Joint Institute; LLC
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: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
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: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Praha-Nusle
country: Czechia
facility: Revmatologicka ambulance
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: Bekescsaba
country: Hungary
facility: Rethy Pal Korhaz es Rendelointezet
city: Budapest,
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Orszgos Reumatolgiai s Fizioterpis Intzet
city: Budapest
country: Hungary
facility: Revita Clinic Rheumatology
city: Debrecen
country: Hungary
facility: Kenezy Hospital Institute of Clinical Pharmacology
city: México
country: Mexico
facility: Cliditer S.A. de C.V.
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Dr Javier Orozco Alcala Private Doctor´s office
city: Morelia
country: Mexico
facility: Centro de Investigacion Clinica de Morelia, S.C.
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
Study officials:
affiliation: Astellas Pharma Global Development
name: Senior Medical Director
role: STUDY_DIRECTOR
References:
citation: Toyoshima J, Shibata M, Kaibara A, Kaneko Y, Izutsu H, Nishimura T. Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis. Br J Clin Pharmacol. 2021 Apr;87(4):2014-2022. doi: 10.1111/bcp.14605. Epub 2020 Dec 1.
citation: Genovese MC, Greenwald M, Codding C, Zubrzycka-Sienkiewicz A, Kivitz AJ, Wang A, Shay K, Wang X, Garg JP, Cardiel MH. Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease-Modifying Antirheumatic Drugs in the Treatment of Moderate-to-Severe Rheumatoid Arthritis. Arthritis Rheumatol. 2017 May;69(5):932-942. doi: 10.1002/art.40054.