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

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT01554696

Collaborator

(none)

379

Enrollment

Locations

Arms

19.2

Actual Duration (Months)

7.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: peficitinib Drug: Placebo Drug: methotrexate	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

379 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 6, 2012

Actual Primary Completion Date :

Feb 11, 2014

Actual Study Completion Date :

Feb 11, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

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