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

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2011-006020-20-PL
• Date of registration: 19/11/2012
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Global Development, Inc. (APGD)
• Public 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
• Scientific 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
• Date of first enrolment: 05/03/2013
• Target sample size: 275
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006020-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Bulgaria, Czech Republic, Hungary, Mexico, Poland, Ukraine, United States

Contacts

• Name: Kathyjo Shay
• Affiliation: Astellas Pharma Global Development, Inc. (APGD)

• Name: Kathyjo Shay
• Affiliation: Astellas Pharma Global Development, Inc. (APGD)

Key inclusion & exclusion criteria

Inclusion criteria:
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) 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) for the treatment of RA 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 (= 3 g/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.
Subjects 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 9), 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, if male, of childbearing potential,
? must 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 an adequate method of 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 last dose offinal 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
Exclusion criteria:
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 taken one of the following oral DMARDs within 28 days prior to the first dose of study drug:
• Methotrexate
• Sulfasalazine
• Hydroxychloroquine
• Gold
• Penicillamine
• Leflunomide
10. Subject has a previous intolerance to JAK inhibitors.
11. 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.
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
17. Subject has a history of heart failure, defi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 14.1 Level: LLT Classification code 10042952 Term: Systemic rheumatoid arthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: ASP015K
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: ASP015K
Other descriptive name: ASP015K hydrobromide, AS1940150-BR, JKT-201A, 4-{[(1R,2s,3S,5s,7s)-5-Hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide monohydrobromide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: ASP015K
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: ASP015K
Other descriptive name: ASP015K hydrobromide, AS1940150-BR, JKT-201A, 4-{[(1R,2s,3S,5s,7s)-5-Hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide monohydrobromide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: ASP015K
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: ASP015K
Other descriptive name: ASP015K hydrobromide, AS1940150-BR, JKT-201A, 4-{[(1R,2s,3S,5s,7s)-5-Hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide monohydrobromide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Week 12

Main Objective: The objective of this study is to evaluate the safety and efficacy of ASP015K in moderate to severe Rheumatoid Arthritis (RA) subjects.

Primary end point(s): The primary efficacy endpoint, ACR20 response rate at Week 12, will be analyzed using a logistic regression model including treatment group and center as explanatory variables. Subjects who withdraw before Week 12 will be counted as non-responders.
The hypothesis for comparisons is given as follows:
H0: The ACR20 response rates at end of treatment for ASP015K and placebo are the same
H1: The ACR20 response rates at end of treatment for ASP015K and placebo are not the same
Comparisons to placebo will be performed at each ASP015K dose level. This study will not consider adjustments for multiplicity, since it is not a pivotal study. The primary analysis will be conducted using the FAS.

Secondary Outcome(s)

Secondary end point(s): For secondary efficacy endpoints, the binary variables ACR50 and ACR70 response rates at Week 12 will be analyzed with a model similar to the primary analysis, and the continuous variable Change from Baseline/Day 1 to Week 12/ET in DAS28-CRP score will be analyzed using a three-way ANOVA model with the same factors as in the primary analysis, as well as interaction terms, as appropriate.

Timepoint(s) of evaluation of this end point: Week 12

Secondary ID(s)

015K-CL-RA22

2011-006020-20-HU

Source(s) of Monetary Support

Astellas Pharma Global Development, Inc. (APGD)