A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02308163
• Date of registration: 02/12/2014
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Inc
• Public title: A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs
• Scientific title: Phase 3 Study of ASP015K - A Randomized, Double-blind, Placebo-controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis Who Had an Inadequate Response to DMARDs
• Date of first enrolment: August 8, 2014
• Target sample size: 509
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02308163
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Japan, Korea, Republic of, Taiwan

Contacts

• Name: Medical Director
• Affiliation: Astellas Pharma Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR)
criteria or the 2010 American College of Rheumatology/European League against
Rheumatism (ACR/EULAR) criteria

- Subject who did not receive the following drugs, or received the drugs with stable
dosage for at least 28 days prior to the baseline (start of treatment) for RA
treatment:

- Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations),
oral morphine or equivalent opioid analgesics (= 30 mg/day), acetaminophen, or
oral corticosteroids (= 10 mg/day in prednisolone equivalent)

- At screening subject has active RA as evidenced by both of the following:

- = 6 tender/painful joints (using 68-joint assessment)

- = 6 swollen joints (using 66-joint assessment)

- CRP > 0.50 mg/dL at screening

- Subject meets the ACR 1991 Revised Criteria for the Classification of Global
Functional Status in RA Class I, II or, III at screening.

- Inadequate responder to (including subjects who were intolerant of) at least one DMARD
administered for at least 90 days prior to screening

Exclusion Criteria:

- Subject has received a biologic DMARD within the specified period

- Subject has received etanercept

- Inadequate responder to at least 3 biologic DMARDs as determined by
investigator/sub-investigator

- Subject has received intra-articular, intravenous, intramuscular or endorectal
(excluding suppositories for anal diseases) corticosteroid within 28 days prior to
baseline

- Subject has participated in any study of ASP015K and has received ASP015K or placebo

- Subject has received other investigational drugs within 90 days or within 5
half-lives, whichever is longer, prior to baseline

- Subject has received plasma exchange therapy within 60 days prior to baseline

- Subject has undergone joint drainage, has received local anesthesia and nerve block,
or has received articular cartilage protectant at the assessed joint within 28 days
prior to baseline

- Subject has undergone surgery and has residual effects in the assessed joints at the
discretion of investigator/sub-investigator, or is scheduled to undergo surgery that
may affect the study evaluation of the assessed joints at the discretion of
investigator/sub-investigator

- A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis,
SLE, sarcoidosis, etc.) other than RA

- Any of the following laboratory values at screening:

- Hemoglobin < 9.0 g/dL

- Absolute neutrophil count < 1000/µL

- Absolute lymphocyte count < 800/µL

- Platelet count < 75000/µL

- ALT = 2 ×ULN

- AST = 2 × ULN

- Total bilirubin (TBL) = 1.5 × ULN

- Estimated GFR = 40 mL/min as measured by the MDRD method

- ß-D-glucan > ULN [in case of Japan: = 11 pg/mL]

- Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation
(However, subject with negative HBs antigen and HBV-DNA quantitation, and
positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by
HBV-DNA quantitation at every scheduled visit after initiation of study drug or
reference drug administration.)

- Positive HCV antibody

- Subject has a history of or concurrent active tuberculosis (TB)

- Subject has a history of or concurrent interstitial pneumonia and
investigator/sub-investigator judges that it is inappropriate for the subject to
participate in this study

- Subject has a history of or concurrent malignant tumor (except for successfully
treated basal cell carcinoma)

- Subject has received live or live attenuated virus vaccination within 56 days prior to
baseline. (Inactivated vaccines including influenza and pneumococcal vaccines are
allowed.)

- Subject has a history of or concurrent demyelinating disorders

- Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac,
neurological, infectious, or autoimmune disease except for RA (excluding Sjogren's
syndrome and chronic thyroiditis), or any ongoing illness which would make the subject
unsuitable for the study as determined by the investigator/sub-investigator

- Subject has a history of clinically significant allergy. (Clinically significant
allergy includes allergies such as systemic urticaria induced by specific antigens and
drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized
treatment.)

- Subject has concurrent cardiac failure, defined as NYHA classification Class III or
higher, or a history of it

- Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged
QT interval (defined as QTc = 500 msec. Subject has QTc = 500 msec at retest will be
excluded) at screening

- Subject has a history of positive HIV infection

- Subject has congenital short QT syndrome or a history of it. Subject has shortened QT
interval (defined as QTc < 330 msec. Subject has QTc < 330 msec at retest will be
excluded) at screening.



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Biological: Etanercept

Drug: Peficitinib

Drug: Placebo

Primary Outcome(s)

Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12 [Time Frame: Baseline and Week 12/early termination (ET)]

Secondary Outcome(s)

Change From Baseline in CRP Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in DAS28-ESR Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in Physician's Global Assessment of Arthritis (PGA) at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in Short Form Health Survey - 36 Questions, Version 2 (SF-36v2) Physical Component Summary Score at Week 12 [Time Frame: Baseline and Week 12/ET]

Percentage of Participants Achieving ACR / EULAR Remission at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants Achieving CDAI Score <= 2.8 Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in CDAI Score at Week 12 [Time Frame: Baseline and Week 12/ET]

Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Score <= 2.8 at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants Achieving DAS28-CRP <= 3.2 at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants Achieving DAS28-CRP <= 3.2 Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants Achieving DAS28-ESR <= 3.2 at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants Achieving SDAI Remission Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12 [Time Frame: Week 12/ET]

Change From Baseline in CDAI Score Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in SDAI Score at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in WPAI Percent Activity Impairment Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Percentage of Participants Achieving DAS28-ESR <= 3.2 Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in ESR at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in PGA Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Change From Baseline in CRP at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (ESR) at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in ESR Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With a Good EULAR Response Using DAS28-ESR at Week 12 [Time Frame: Week 12/ET]

Change From Baseline in HAQ-DI Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With a Good EULAR Response Using DAS28-ESR Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in SJC (66 Joints) Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Number of Participants Who Withdrew Due to Lack of Efficacy [Time Frame: Up to week 12]

Number of Participants With Adverse Events During the First 12 Weeks [Time Frame: Week 0 to Week 12]

Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR at Week 12 [Time Frame: Week 12/ET]

Change From Baseline in SDAI Score Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants With an American College of Rheumatology 70% (ACR70)-CRP Response at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in Subject's SGA at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in TJC (68 Joints) at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in WPAI Percent Impairment While Working at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in WPAI Percent Work Time Missed Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Change From Baseline in TJC (68 Joints) Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants Achieving DAS28-ESR < 2.6 at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants Achieving DAS28-ESR < 2.6 Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in SGA Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Number of Participants With Adverse Events From Week 12 [Time Frame: Week 12 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study]

Percentage of Participants With a EULAR Good Response Using DAS28-CRP Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With an ACR20-CRP Response Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in Subject's Assessment of Pain Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With an ACR70-CRP Response Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in WPAI Percent Overall Work Impairment Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Percentage of Participants Achieving ACR / EULAR Remission Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With an American College of Rheumatology 50% (ACR50)-CRP Response at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline DAS28-CRP Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Change From Baseline in Percent Overall Work Impairment at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Change From Baseline in Subject's Assessment of Pain at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in WPAI Percent Activity Impairment at Week 12 [Time Frame: Baseline and Week 12/ET]

Change From Baseline in WPAI Percent Impairment While Working Through Week 52 [Time Frame: Baseline and Week 4, 8, 12, 28, and 52]

Percentage of Participants Achieving DAS28-CRP < 2.6 at Week 12 [Time Frame: Baseline and Week 12/ET]

Percentage of Participants Achieving DAS28-CRP < 2.6 Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission at Week 12 [Time Frame: Week 12/ET]

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR Through Week 52 [Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Percentage of Participants With an ACR50-CRP Response Through Week 52 [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52]

Secondary ID(s)

015K-CL-RAJ3

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/03/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02308163