A clinical study of ASP015K in patients with moderate to severe rheumatoid arthritis (RA)
- Conditions
- Rheumatoid ArthritisMedDRA version: 14.1Level: LLTClassification code 10042952Term: Systemic rheumatoid arthritisSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2011-006020-20-BG
- Lead Sponsor
- Astellas Pharma Global Development, Inc. (APGD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 275
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the Subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Male or female subject is at least 18 years of age at the time of Informed Consent.
3. Subject has RA that was diagnosed according to the 1987 revised criteria of the American College of Rheumatology (ACR) (Appendix 5) at least 6 months prior to Screening and have had an inadequate response or had intolerance to a previous disease modifying anti-rheumatic disease
(DMARD) therapy.
4. Subject’s other related medication taken for the treatment of RA at the time of Screening must meet the following stability requirements:
? Non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and oral corticosteroids (= 10 mg of prednisone, or equivalent, daily) must be stable for at least 28 days prior to the start of study drug.
? Hydroxychloroquine (= 400 mg/day), chloroquine (= 250 mg/day) and sulfasalazine (= 3g/day) must have been started at least 60 days prior to the start of study drug and must be stable for at least 28 days prior to the start of study drug.
5. Subject has active rheumatoid arthritis as evidenced by the following:
? =6 tender/painful joints (using 68-joint assessment);
? =6 swollen joints (using 66-joint assessment); and
? C-Reactive Protein (CRP) of = 0.8 mg/dL or Erythrocyte Sedimentation Rate (ESR) of = 28 mm/hr at Screening.
Subject must continue to meet both joint count criteria at the Baseline visit prior to being randomized.
6. Subject meets the ACR 1991 Revised Criteria for Global Functional Status in RA (Appendix 6), Class I, II or III at Screening and Baseline.
7. Female subject must be either:
• Of non-childbearing potential:
? post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
? documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)
• Or, of childbearing potential:
? must agree to have a negative serum pregnancy test at Screening, and
? must use two forms of birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period, and for 60 days after the final study drug administration.
8. Female subject must not be breastfeeding at Screening or during the study period, and for 60 days after the final study drug administration.
9. Female subject must not donate ova starting at Screening and
throughout the study period, and for 60 days after the final study drug administration
10. Male subject and their female spouse/partners who are of
childbearing potential must be using highly effective contraception
consisting of two forms of birth control* (one of which must be a barrier method ) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration
11. Male subject must not donate sperm starting at Screening and
throughout the study period and for 90 days after the final study drug administration.
12. Subject must be willing and able to comply with the study
requirements.
13. Subject agrees not to participate in another interventional study
Subject will be excluded from participation if any of the following apply:
1. Subject currently has or has a history of a positive Mycobacterium tuberculosis (TB) test and does not have documentation of completion of a recommended course of antimicrobial therapy per local guidelines.
2. Subject has an abnormal chest x-ray within 90 days of or at Screening indicative of an acute or chronic infectious process or malignancy.
3. Subject has received live or live attenuated virus vaccination within 30 days prior to the first dose of study drug.
4. Subject has a 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.
5. Subject has a history of any other autoimmune rheumatic disease, other than Sjogren’s syndrome.
6. Subject has a 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 in the investigator’s opinion would preclude participation in the study.
7. Subject has a history of any malignancy, except for successfully treated basal or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix.
8. Subject has taken any of the following DMARDs and/or biologic agents within the specified period prior to the first dose of study drug:
? Methotrexate, gold, azathioprine, minocycline, and penicillamine - 28 days
? Etanercept – 28 days
? Certolizumab, adalimumab, golimumab, infliximab and tocilizumab – 60 days
? Rituximab or any other CD20 inhibitors – 180 days
? Abatacept – 90 days
? Anakinra – 7 days
? Cyclophosphamide - 180 days
? Leflunomide – 60 days; if the subject has undergone a cholestyramine washout, then the washout is reduced to 30 days prior to Day 1 dosing
9. Subject has a previous intolerance to JAK inhibitors.
10. Subject has received intra-articular or parenteral (intravenous [IV], subcutaneous, intramuscular) 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.
11. Subject has received plasma exchange therapy within 60 days prior to the start of study drug.
12. Subject has previously received ASP015K.
13. Subject has received any investigational agent within 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
14. Subject has received medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to first dose of study drug. These medications include but are not limited to: alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, and terfenadine.
15. Subject has any of the following laboratory values at Screening:
? Hemoglobin < 10 g/dL
? White blood cell count < 3000/mm3
? Absolute neutrophil count (ANC) < 2000/mm3
? Absolute lymphocyte count (ALC) < 750/mm3
? Platelet count < 100,000/mm3
? ALT = 2 x upper limit of normal
? AST = 2 x upper limit of normal
? Total bilirubin = 1.5 x upper limit of normal
? Estimated GFR = 40 mL/min/1.73 m2, as measured by the Modification of Diet in Renal Disease (MDRD) method
? CPK > 1.5 x upper limit of normal
16. Subject has a history of heart failure, defined as New York Heart Association (NYHA) grade 3 or greater.
17. Subject has a history of long QT syndrome or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method