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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01554696
First received: March 13, 2012
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Arthritis, Rheumatoid
Drug: ASP015K
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Subjects Who Have Had an Inadequate Response to Methotrexate

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Percentage of subjects achieving American College of Rheumatology Criteria 20 (ACR 20) response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Trough plasma concentration of ASP015K and metabolite(s) [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects achieving ACR 50 response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percentage of subjects achieving ACR 70 response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 379
Study Start Date: June 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASP015K lowest dose
ASP015K lowest dose daily in addition to concomitant weekly oral methotrexate
Drug: ASP015K
oral
Experimental: ASP015K low dose
ASP015K low dose daily in addition to concomitant weekly oral methotrexate
Drug: ASP015K
oral
Experimental: ASP015K medium dose
ASP015K medium dose daily in addition to concomitant weekly oral methotrexate
Drug: ASP015K
oral
Experimental: ASP015K high dose
ASP015K high dose daily in addition to concomitant weekly oral methotrexate
Drug: ASP015K
oral
Placebo Comparator: Placebo
Placebo daily in addition to concomitant weekly oral methotrexate
Drug: Placebo
oral

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01554696

  Show 49 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Senior Medical Director Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01554696     History of Changes
Other Study ID Numbers: 015K-CL-RA21, 2011-006018-15
Study First Received: March 13, 2012
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Mexico: Federal Commission for Sanitary Risks Protection
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Astellas Pharma Inc:
Rheumatoid Arthritis
ASP015K

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014