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

NCT ID: NCT02308163

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 509 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-08
• Study Completion Date: 2017-11-22

Brief Summary

The objective of this study was to verify the superiority of ASP015K alone or in combination with disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response to DMARDs

Detailed Description

This was a multi-center, randomized, placebo-controlled, double-blind, parallel-group, confirmatory study to evaluate the efficacy and safety of ASP015K alone or in combination with DMARDs in participants with RA who had an inadequate response to DMARDs.

Etanercept was also administered as the reference drug in an open-label manner. The study drug was orally administered once daily (QD) after breakfast for 52 weeks. Etanercept was administered subcutaneously QD for 52 weeks. At Week 12, participants in the placebo group were switched to ASP015K.

The dose of ASP015K to be started at Week 12 for the placebo group was determined randomly at baseline in advance and switched in a blinded manner.

Participants in ASP015K group or placebo groups who had completed the study were eligible for participation in an open-label extension study (015K-CL-RAJ2).

Conditions

Rheumatoid Arthritis

Study Design

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

Study Groups

Placebo

Participants were assigned to receive placebo to peficitinib once a day until week 12.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral

Peficitinib 100 mg

Participants were assigned to receive peficitinib 100 mg/day for 52 weeks.

Group Type: EXPERIMENTAL

Peficitinib

Intervention Type: DRUG

oral

Peficitinib 150 mg

Participants were assigned to receive peficitinib 150 mg/day for 52 weeks.

Group Type: EXPERIMENTAL

Peficitinib

Intervention Type: DRUG

oral

Etanercept

Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.

Group Type: ACTIVE_COMPARATOR

Etanercept

Intervention Type: BIOLOGICAL

subcutaneous injection

Interventions

Peficitinib

oral

Intervention Type: DRUG

Placebo

oral

Intervention Type: DRUG

Etanercept

subcutaneous injection

Intervention Type: BIOLOGICAL

Other Intervention Names

ASP015K

Eligibility 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
• β-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.

• 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

JP00066

Okazaki, Aichi-ken, Japan

JP00140

Toyoake, Aichi-ken, Japan

JP00108

Toyohashi, Aichi-ken, Japan

JP00156

Toyota, Aichi-ken, Japan

JP00068

Yatomi, Aichi-ken, Japan

JP00102

Kamagaya, Chiba, Japan

JP00127

Matsudo, Chiba, Japan

JP00115

Narashino, Chiba, Japan

JP00138

Yotsukaidō, Chiba, Japan

JP00120

Iizuka, Fukuoka, Japan

JP00040

Kitakyushu, Fukuoka, Japan

JP00119

Kitakyushu, Fukuoka, Japan

JP00071

Kurume, Fukuoka, Japan

JP00097

Kurume, Fukuoka, Japan

JP00106

Kurume, Fukuoka, Japan

JP00033

Takasaki, Gunma, Japan

JP00026

Asahikawa, Hokkaido, Japan

JP00090

Hakodate, Hokkaido, Japan

JP00125

Kushiro, Hokkaido, Japan

JP00001

Sapporo, Hokkaido, Japan

JP00002

Sapporo, Hokkaido, Japan

JP00003

Sapporo, Hokkaido, Japan

JP00031

Sapporo, Hokkaido, Japan

JP00038

Sapporo, Hokkaido, Japan

JP00114

Sapporo, Hokkaido, Japan

JP00158

Sapporo, Hokkaido, Japan

JP00056

Akashi, Hyōgo, Japan

JP00069

Himeji, Hyōgo, Japan

JP00113

Kakogawa, Hyōgo, Japan

JP00041

Katō, Hyōgo, Japan

JP00042

Kobe, Hyōgo, Japan

JP00092

Kobe, Hyōgo, Japan

JP00154

Kobe, Hyōgo, Japan

JP00117

Nishinomiya, Hyōgo, Japan

JP00107

Hitachi, Ibaraki, Japan

JP00073

Koga, Ibaraki, Japan

JP00054

Mito, Ibaraki, Japan

JP00049

Morioka, Iwate, Japan

JP00084

Isehara, Kanagawa, Japan

JP00048

Kawasaki, Kanagawa, Japan

JP00058

Kawasaki, Kanagawa, Japan

JP00141

Sagamihara, Kanagawa, Japan

JP00096

Yokohama, Kanagawa, Japan

JP00128

Yokosuka, Kanagawa, Japan

JP00057

Tamana, Kumamoto, Japan

JP00004

Sendai, Miyagi, Japan

JP00027

Sendai, Miyagi, Japan

JP00036

Sendai, Miyagi, Japan

JP00105

Sendai, Miyagi, Japan

JP00151

Sendai, Miyagi, Japan

JP00050

Hyūga, Miyazaki, 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

JP00078

Kawachi-Nagano, Osaka, Japan

JP00137

Sakai, Osaka, Japan

JP00070

Suita, Osaka, Japan

JP00086

Suita, Osaka, Japan

JP00061

Toyonaka, Osaka, Japan

JP00075

Ureshino, Saga-ken, Japan

JP00126

Gyōda, Saitama, Japan

JP00007

Hiki, Saitama, Japan

JP00082

Iruma, 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

JP00024

Bunkyo, Tokyo, Japan

JP00043

Bunkyo, Tokyo, Japan

JP00149

Bunkyo, Tokyo, Japan

JP00152

Bunkyo, Tokyo, Japan

JP00095

Chiyoda City, Tokyo, Japan

JP00099

Chiyoda City, Tokyo, Japan

JP00142

Chūō, Tokyo, Japan

JP00063

Hachiōji, Tokyo, Japan

JP00053

Kiyose, Tokyo, Japan

JP00072

Meguro City, Tokyo, Japan

JP00083

Meguro City, Tokyo, Japan

JP00148

Ōta-ku, Tokyo, Japan

JP00100

Setagaya City, Tokyo, Japan

JP00032

Shinjuku, Tokyo, Japan

JP00010

Takaoka, Toyama, Japan

JP00155

Nishimuro, Wakayama, Japan

JP00104

Shimonoseki, Yamaguchi, Japan

JP00047

Shūnan, Yamaguchi, 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

JP00013

Hiroshima, , Japan

JP00014

Hiroshima, , Japan

JP00015

Hiroshima, , Japan

JP00016

Hiroshima, , Japan

JP00055

Hiroshima, , Japan

JP00065

Kagoshima, , Japan

JP00074

Kagoshima, , Japan

JP00093

Kochi, , Japan

JP00022

Kumamoto, , Japan

JP00046

Kumamoto, , Japan

JP00123

Kyoto, , Japan

JP00159

Kyoto, , Japan

JP00023

Miyagi, , Japan

JP00122

Miyazaki, , Japan

JP00080

Nagano, , Japan

JP00098

Nagasaki, , Japan

JP00112

Nagasaki, , Japan

JP00147

Nagasaki, , Japan

JP00118

Okayama, , Japan

JP00150

Osaka, , Japan

JP00157

Osaka, , Japan

JP00017

Ōita, , Japan

JP00089

Shizuoka, , Japan

JP00135

Shizuoka, , Japan

JP00139

Toyama, , Japan

KR00504

Daegu, , South Korea

KR00510

Daegu, , South Korea

KR00505

Gwangju, , South Korea

KR00506

Incheon, , South Korea

KR00508

Jeonju, , South Korea

KR00501

Seoul, , South Korea

KR00502

Seoul, , South Korea

KR00503

Seoul, , South Korea

KR00509

Seoul, , South Korea

KR00511

Seoul, , South Korea

KR00507

Suwon, , South Korea

TW00708

Kaohsiung City, , Taiwan

TW00709

Kaohsiung City, , Taiwan

TW00704

Taichung, , Taiwan

TW00705

Taichung, , Taiwan

TW00710

Taichung, , Taiwan

TW00712

Tainan City, , Taiwan

TW00701

Taipei, , Taiwan

TW00702

Taipei, , Taiwan

TW00711

Taipei, , Taiwan

TW00703

Taoyuan District, , Taiwan

Countries

Japan; South Korea; Taiwan

References

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)

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)

Tanaka Y, Takeuchi T, Tanaka S, Kawakami A, Iwasaki M, Song YW, Chen YH, Wei JC, Lee SH, Rokuda M, Izutsu H, Ushijima S, Kaneko Y, Akazawa R, Shiomi T, Yamada E. Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3). Ann Rheum Dis. 2019 Oct;78(10):1320-1332. doi: 10.1136/annrheumdis-2019-215163. Epub 2019 Jul 26.

Reference Type: DERIVED

PMID: 31350270 (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=335

Link to results on Astellas Clinical Study Results website

Other Identifiers

015K-CL-RAJ3

Identifier Type: -

Identifier Source: org_study_id