A Study to Evaluate Efficacy and Safety of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to Methotrexate (MTX) Treatment
Phase 3 Study of ASP015K - A Randomized, Double-blind, Placebo-controlled Confirmatory Study of the Efficacy and Safety of ASP015K in Patients With Rheumatoid Arthritis Who Had an Inadequate Response to MTX
1 other identifier
interventional
519
1 country
146
Brief Summary
The objective of this study was to verify the efficacy of ASP015K versus placebo administrated in combination with methotrexate (MTX) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response to MTX
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 rheumatoid-arthritis
Started Jul 2014
Typical duration for phase_3 rheumatoid-arthritis
146 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 25, 2014
CompletedFirst Submitted
Initial submission to the registry
December 1, 2014
CompletedFirst Posted
Study publicly available on registry
December 3, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 20, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 28, 2017
CompletedResults Posted
Study results publicly available
August 3, 2020
CompletedOctober 28, 2024
October 1, 2024
2.9 years
December 1, 2014
June 3, 2020
October 17, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12
ACR20 response: greater than and equal to (≥) 20 percent (%) improvement in tender and swollen joint count; and ≥ 20% improvement in at least 3 of the following 5 criteria compared with baseline: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
Baseline and week 12/Early termination (ET)
Change From Baseline in mTSS at Week 28
mTSS was defined as the sum of joint erosion scores graded by assessing erosion severity in 44 joints (16 per hand and 6 per feet) and JSN scores graded by assessing narrowing of joint spaces in 42 joints (15 per hand and 6 per feet). Erosion score was scored from 0 (no erosion) to 5 (complete collapse of bone) and the score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). JSN including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change from baseline was calculated as score at week 28 (ET) minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Baseline and week 28/ET
Secondary Outcomes (69)
Percentage of Participants With an ACR20-CRP Response Through Week 52
Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT
Percentage of Participants With an ACR50-CRP Response at Week 12
Baseline and week 12/ET
Percentage of Participants With an ACR50-CRP Response Through Week 52
Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT
Percentage of Participants With an ACR70-CRP Response at Week 12
Baseline and week 12/ET
Percentage of Participants With an ACR70-CRP Response Through Week 52
Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT
- +64 more secondary outcomes
Study Arms (3)
Peficitinib 100 mg
EXPERIMENTALParticipants received 100 mg tablet of peficitinib orally once daily in combination with MTX for a period of 52 weeks.
Peficitinib 150 mg
EXPERIMENTALParticipants received 150 mg tablet of peficitinib orally once daily in combination with MTX for a period of 52 weeks.
Placebo
PLACEBO COMPARATORParticipants who received placebo matching to peficitinib 100 mg or 150 mg orally once daily in combination with MTX until week 12 or 28 were switched to receive 100 mg or 150 mg tablet of peficitinib orally once daily in combination with MTX from week 12 or 28 to week 52.
Interventions
Eligibility Criteria
You may qualify if:
- Subject has RA of \< 10 years duration at baseline that was 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 with a local action), 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 (latex agglutination test) of ≥ 1.00 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 responders to MTX which was continuously administered for at least 90 days prior to screening and MTX ≥ 8 mg/week for at least 28 days prior to baseline. However, inadequate responder to MTX \< 8 mg/week is eligible if intolerance precludes dose increase and defined as MTX-IR
- Subject is able to continue stable dose of MTX (a maximum of 16 mg/week) from at least 28 days prior to screening until the end of treatment
- Subject has bone erosion at the joint (as evidenced by x-rays of hands and feet) assessed in mTSS and any of the following apply at screening. Bone erosion may be evidenced by x-rays within 90 days prior to baseline.
- Positive anti-CCP antibody: ≥ 4.5 U/mL
- Positive rheumatoid factor: \> 15 IU/mL
You may not qualify if:
- Subject has received a biologic DMARD within the specified period
- Inadequate responders to biologic DMARD 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
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (146)
JP00037
Nagoya, Aichi-ken, Japan
JP00109
Nagoya, Aichi-ken, Japan
JP00130
Nagoya, Aichi-ken, Japan
JP00175
Nagoya, Aichi-ken, Japan
JP00066
Okazaki, Aichi-ken, Japan
JP00108
Toyohashi, Aichi-ken, Japan
JP00170
Toyohashi, Aichi-ken, Japan
JP00156
Toyota, Aichi-ken, Japan
JP00068
Yatomi, Aichi-ken, Japan
JP00180
Asahi, Chiba, Japan
JP00166
Funabashi, Chiba, Japan
JP00115
Narashino, Chiba, Japan
JP00138
Yotsukaidō, Chiba, Japan
JP00120
Iizuka, Fukuoka, Japan
JP00110
Kasuga, Fukuoka, Japan
JP00040
Kitakyushu, Fukuoka, Japan
JP00119
Kitakyushu, Fukuoka, Japan
JP00071
Kurume, Fukuoka, Japan
JP00106
Kurume, Fukuoka, Japan
JP00033
Takasaki, Gunma, Japan
JP00163
Higashihiroshima, Hiroshima, Japan
JP00124
Tomakomai, Hokaido, Japan
JP00026
Asahikawa, Hokkaido, Japan
JP00090
Hakodate, Hokkaido, Japan
JP00172
Kitami, Hokkaido, Japan
JP00125
Kushiro, Hokkaido, Japan
JP00001
Sapporo, Hokkaido, Japan
JP00002
Sapporo, Hokkaido, Japan
JP00003
Sapporo, Hokkaido, Japan
JP00038
Sapporo, Hokkaido, Japan
JP00114
Sapporo, Hokkaido, Japan
JP00056
Akashi, Hyōgo, Japan
JP00069
Himeji, Hyōgo, Japan
JP00136
Itami, Hyōgo, Japan
JP00113
Kakogawa, Hyōgo, Japan
JP00041
Katō, Hyōgo, Japan
JP00042
Kobe, Hyōgo, Japan
JP00092
Kobe, Hyōgo, Japan
JP00154
Kobe, Hyōgo, Japan
JP00171
Kobe, Hyōgo, Japan
JP00117
Nishinomiya, Hyōgo, Japan
JP00107
Hitachi, Ibaraki, Japan
JP00181
Hitachi-Naka, Ibaraki, Japan
JP00073
Koga, Ibaraki, Japan
JP00054
Mito, Ibaraki, Japan
JP00039
Tsukuba, Ibaraki, Japan
JP00179
Komatsu, Ishikawa-ken, Japan
JP00049
Morioka, Iwate, Japan
JP00088
Kida, Kagawa-ken, Japan
JP00084
Isehara, Kanagawa, Japan
JP00048
Kawasaki, Kanagawa, Japan
JP00058
Kawasaki, Kanagawa, Japan
JP00141
Sagamihara, Kanagawa, Japan
JP00096
Yokohama, Kanagawa, Japan
JP00045
Zushi, Kanagawa, Japan
JP00019
Kōshi, Kumamoto, Japan
JP00057
Tamana, Kumamoto, Japan
JP00168
Yokkaichi, Mie-ken, Japan
JP00169
Ōsaki, Miyagi, Japan
JP00004
Sendai, Miyagi, Japan
JP00036
Sendai, Miyagi, Japan
JP00105
Sendai, Miyagi, Japan
JP00151
Sendai, Miyagi, Japan
JP00050
Hyūga, Miyazaki, Japan
JP00129
Matsumoto, Nagano, Japan
JP00162
Isehaya, Nagasaki, Japan
JP00101
Ōmura, Nagasaki, Japan
JP00103
Ōmura, Nagasaki, Japan
JP00153
Sasebo, Nagasaki, Japan
JP00094
Kashihara, Nara, Japan
JP00025
Nagaoka, Niigata, Japan
JP00144
Shibata, Niigata, Japan
JP00064
Beppu, Oita Prefecture, Japan
JP00051
Setouchi, Okayama-ken, Japan
JP00011
Hannan, Osaka, Japan
JP00134
Higashiosaka, Osaka, Japan
JP00178
Hirakata, Osaka, Japan
JP00078
Kawachi-Nagano, Osaka, Japan
JP00137
Sakai, Osaka, Japan
JP00070
Suita, Osaka, Japan
JP00146
Suita, Osaka, Japan
JP00061
Toyonaka, Osaka, Japan
JP00075
Ureshino, Saga-ken, Japan
JP00126
Gyōda, Saitama, Japan
JP00007
Hiki, Saitama, Japan
JP00060
Kawagoe, Saitama, Japan
JP00161
Kawagoe, Saitama, Japan
JP00062
Kawaguchi, Saitama, Japan
JP00052
Sayama, Saitama, Japan
JP00008
Tokorozawa, Saitama, Japan
JP00133
Kakegawa, Shizuoka, Japan
JP00077
Kanuma, Tochigi, Japan
JP00145
Shimotsuke, Tochigi, Japan
JP00024
Bunkyo, Tokyo, Japan
JP00143
Bunkyo, Tokyo, Japan
JP00149
Bunkyo, Tokyo, Japan
JP00152
Bunkyo, Tokyo, Japan
JP00099
Chiyoda City, Tokyo, Japan
JP00142
Chūō, Tokyo, Japan
JP00063
Hachiōji, Tokyo, Japan
JP00053
Kiyose, Tokyo, Japan
JP00072
Meguro City, Tokyo, Japan
JP00148
Ōta-ku, Tokyo, Japan
JP00081
Shibuya City, Tokyo, Japan
JP00010
Takaoka, Toyama, Japan
JP00155
Nishimuro, Wakayama, Japan
JP00104
Shimonoseki, Yamaguchi, Japan
JP00047
Shūnan, Yamaguchi, Japan
JP00176
Fukui, Japan
JP00018
Fukuoka, Japan
JP00020
Fukuoka, Japan
JP00035
Fukuoka, Japan
JP00059
Fukuoka, Japan
JP00067
Fukuoka, Japan
JP00076
Fukuoka, Japan
JP00131
Fukuoka, Japan
JP00164
Fukuoka, Japan
JP00165
Fukushima, Japan
JP00013
Hiroshima, Japan
JP00014
Hiroshima, Japan
JP00016
Hiroshima, Japan
JP00055
Hiroshima, Japan
JP00074
Kagoshima, Japan
JP00167
Kagoshima, Japan
JP00093
Kochi, Japan
JP00022
Kumamoto, Japan
JP00046
Kumamoto, Japan
JP00085
Kyoto, Japan
JP00123
Kyoto, Japan
JP00160
Kyoto, Japan
JP00023
Miyagi, Japan
JP00122
Miyazaki, Japan
JP00080
Nagano, Japan
JP00174
Nagano, Japan
JP00098
Nagasaki, Japan
JP00112
Nagasaki, Japan
JP00147
Nagasaki, Japan
JP00118
Okayama, Japan
JP00150
Osaka, Japan
JP00157
Osaka, Japan
JP00177
Osaka, Japan
JP00017
Ōita, Japan
JP00044
Shizuoka, Japan
JP00089
Shizuoka, Japan
JP00135
Shizuoka, Japan
JP00139
Toyama, Japan
Related Publications (5)
Tanaka Y, Takeuchi T, Kato D, Kaneko Y, Fukuda M, Izutsu H, Rokuda M, van der Heijde D. Post hoc analysis of clinical characteristics of patients with radiographic progression in a Japanese phase 3 trial of peficitinib and methotrexate treatment (RAJ4). Mod Rheumatol. 2023 Jan 3;33(1):73-80. doi: 10.1093/mr/roac021.
PMID: 35267027DERIVEDTanaka Y, Takeuchi T, Izutsu H, Kaneko Y, Kato D, Fukuda M, Rokuda M, Schultz NM. Patient- and physician-reported outcomes from two phase 3 randomized studies (RAJ3 and RAJ4) of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis. Arthritis Res Ther. 2021 Aug 24;23(1):221. doi: 10.1186/s13075-021-02590-z.
PMID: 34429152DERIVEDToyoshima J, Kaibara A, Shibata M, Kaneko Y, Izutsu H, Nishimura T. Exposure-response modeling of peficitinib efficacy in patients with rheumatoid arthritis. Pharmacol Res Perspect. 2021 May;9(3):e00744. doi: 10.1002/prp2.744.
PMID: 33929089DERIVEDToyoshima J, Shibata M, Kaibara A, Kaneko Y, Izutsu H, Nishimura T. Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis. Br J Clin Pharmacol. 2021 Apr;87(4):2014-2022. doi: 10.1111/bcp.14605. Epub 2020 Dec 1.
PMID: 33068028DERIVEDTakeuchi T, Tanaka Y, Tanaka S, Kawakami A, Iwasaki M, Katayama K, Rokuda M, Izutsu H, Ushijima S, Kaneko Y, Shiomi T, Yamada E, van der Heijde D. Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan. Ann Rheum Dis. 2019 Oct;78(10):1305-1319. doi: 10.1136/annrheumdis-2019-215164. Epub 2019 Jul 26.
PMID: 31350269DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 1, 2014
First Posted
December 3, 2014
Study Start
July 25, 2014
Primary Completion
June 20, 2017
Study Completion
November 28, 2017
Last Updated
October 28, 2024
Results First Posted
August 3, 2020
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.