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

NCT ID: NCT02305849

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 519 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-25
• Study Completion Date: 2017-11-28

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

Detailed Description

This study was a multi-center, randomized, placebo-controlled, double-blind, parallel-group, confirmatory study to evaluate the efficacy and safety of ASP015K (100 and 150 mg/day) administered in combination with MTX in participants with RA who had an inadequate response to MTX.

Participants orally received ASP015K 100 mg, ASP015K 150 mg or placebo once daily (QD) in combination with MTX after breakfast for 52 weeks.

At Week 12, inadequate responders in the placebo group, as determined by a < 20% improvement from baseline (i.e., treatment initiation day) in tender or painful joint count (TJC) and swollen joint count (SJC), were switched to either ASP015K 100 mg or ASP015K 150 mg, and the dosage was maintained until the end of treatment (EOT). In addition, participants who received placebo at Week 28 were switched to either ASP015K 100 mg or ASP015K 150 mg, and the dosage was maintained until the EOT.

The ASP015K dose that was started for placebo group participants at Week 12 or Week 28 was randomly chosen at baseline. The dose was switched under the blinded condition.

Participants who completed this study were eligible for participation in the open-label extension study (015K-CL-RAJ2). Participants made a follow-up visit after the week 52 visit if they did not enroll into the extension study on the day of the week 52 visit.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Peficitinib 100 mg

Participants received 100 mg tablet of peficitinib orally once daily in combination with MTX for a period of 52 weeks.

Group Type: EXPERIMENTAL

Peficitinib

Intervention Type: DRUG

oral tablet

Methotrexate

Intervention Type: DRUG

Oral tablet/capsule

Peficitinib 150 mg

Participants received 150 mg tablet of peficitinib orally once daily in combination with MTX for a period of 52 weeks.

Group Type: EXPERIMENTAL

Peficitinib

Intervention Type: DRUG

oral tablet

Methotrexate

Intervention Type: DRUG

Oral tablet/capsule

Placebo

Participants 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral tablet

Methotrexate

Intervention Type: DRUG

Oral tablet/capsule

Interventions

Peficitinib

oral tablet

Intervention Type: DRUG

Placebo

oral tablet

Intervention Type: DRUG

Methotrexate

Oral tablet/capsule

Intervention Type: DRUG

Other Intervention Names

ASP015K

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• AST ≥ 2 × ULN
• Total bilirubin (TBL) ≥ 1.5 × ULN
• Estimated GFR ≤ 40 mL/min as measured by the MDRD method
• β-D-glucan ≥ 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 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 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

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

Countries

Japan

References

Toyoshima 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.

Reference Type: DERIVED

PMID: 33068028 (View on PubMed)

Takeuchi 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.

Reference Type: DERIVED

PMID: 31350269 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35267027 (View on PubMed)

Tanaka 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.

Reference Type: DERIVED

PMID: 34429152 (View on PubMed)

Toyoshima 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.

Reference Type: DERIVED

PMID: 33929089 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://astellasclinicalstudyresults.com/study.aspx?ID=336

Link to results on Astellas Clinical Study Results website

Other Identifiers

015K-CL-RAJ4

Identifier Type: -

Identifier Source: org_study_id