Clinical trial NCT00870467: A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis
Official title: A Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Eisai Co., Ltd.
First posted: 2009-03-27
Enrollment: 334
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the potential of adalimumab to inhibit radiographic progression in joint destruction compared with placebo in adult Japanese subjects with recent onset of rheumatoid arthritis.

Detailed description: This was a Phase 3 multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the inhibition of radiographic progression by adalimumab compared with placebo in adult Japanese patients with early rheumatoid arthritis (RA) who had not been previously treated with methotrexate (MTX). Eligible participants were randomized 1:1 to receive either a subcutaneous injection of adalimumab 40 mg or matching placebo every other week (eow) during the 26-week double-blind phase. All participants also received 6 mg to 8 mg MTX weekly as basal treatment for their disease. Participants who experienced an increase in disease activity (more than 20% increase in tender joint count and swollen joint count) at Week 12, 16, or 20 compared with Baseline after having increased MTX dose to 8 mg per week for at least 4 weeks were discontinued from the double-blind phase and were eligible to receive open-label adalimumab 40 mg eow as rescue treatment. Participants who completed the 26 weeks of treatment (either double-blind study drug \[adalimumab or placebo\] treatment or open-label adalimumab treatment) were eligible to enter the 26-week open-label phase in which they received adalimumab 40 mg eow. Efficacy and safety assessments were performed at Baseline and at designated study visits.

Eligibility criteria: Inclusion Criteria

* Rheumatoid arthritis based on the American College of Rheumatology criteria
* Methotrexate or leflunomide naïve
* Disease duration less than or equal to 2 years from diagnosis

Exclusion Criteria

* History of acute inflammatory joint disease of different origin from rheumatoid arthritis, cancer, lymphoma, leukemia or lymphoproliferative disease, active TB, HIV
* Previously received anti-TNF therapy anti-IL-6 receptor antibody, CTLA4-Ig, anti-CD20 antibody, cyclophosphamide, cyclosporine, azathioprine, or tacrolimus
* Joint surgery involving joints to be assessed within 8 weeks prior to Screening

Primary outcomes:
measure: Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)
timeFrame: Week 26
measure: Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)
timeFrame: Week 26
measure: Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)
timeFrame: Week 26
measure: Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26
timeFrame: Baseline, Week 26
measure: Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26
timeFrame: Week 26
measure: Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26
timeFrame: Through Week 26
measure: Change From Baseline in Modified Total Sharp X-Ray Score at Week 52
timeFrame: Baseline, Week 52
measure: Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)
timeFrame: Week 52
measure: Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)
timeFrame: Week 52
measure: Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)
timeFrame: Week 52
measure: Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52
timeFrame: Baseline, Week 52
measure: Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52
timeFrame: Week 52
measure: Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52
timeFrame: Through Week 52
Other outcomes:
Locations:
city: Anjo
country: Japan
facility: Site Reference ID/Investigator# 46861
city: Aomori
country: Japan
facility: Site Reference ID/Investigator# 46919
city: Chiba
country: Japan
facility: Site Reference ID/Investigator# 46805
city: Chiba
country: Japan
facility: Site Reference ID/Investigator# 46806
city: Chiba
country: Japan
facility: Site Reference ID/Investigator# 46880
city: Chiba
country: Japan
facility: Site Reference ID/Investigator# 46881
city: Fuchu
country: Japan
facility: Site Reference ID/Investigator# 46890
city: Fukuoka
country: Japan
facility: Site Reference ID/Investigator# 46902
city: Fukuoka
country: Japan
facility: Site Reference ID/Investigator# 46903
city: Fukuoka
country: Japan
facility: Site Reference ID/Investigator# 46904
city: Gifu
country: Japan
facility: Site Reference ID/Investigator# 46856
city: Gunma
country: Japan
facility: Site Reference ID/Investigator# 46944
city: Hiroshima
country: Japan
facility: Site Reference ID/Investigator# 46893
city: Hiroshima
country: Japan
facility: Site Reference ID/Investigator# 46894
city: Hokkaido
country: Japan
facility: Site Reference ID/Investigator# 12161
city: Hokkaido
country: Japan
facility: Site Reference ID/Investigator# 46916
city: Hokkaido
country: Japan
facility: Site Reference ID/Investigator# 46918
city: Hyogo
country: Japan
facility: Site Reference ID/Investigator# 46865
city: Hyogo
country: Japan
facility: Site Reference ID/Investigator# 46871
city: Ibaraki
country: Japan
facility: Site Reference ID/Investigator# 46801
city: Ibaraki
country: Japan
facility: Site Reference ID/Investigator# 46925
city: Iwate
country: Japan
facility: Site Reference ID/Investigator# 46800
city: Kagoshima
country: Japan
facility: Site Reference ID/Investigator# 46873
city: Kagoshima
country: Japan
facility: Site Reference ID/Investigator# 46874
city: Kanagawa
country: Japan
facility: Site Reference ID/Investigator# 46845
city: Kanagawa
country: Japan
facility: Site Reference ID/Investigator# 46899
city: Kanagawa
country: Japan
facility: Site Reference ID/Investigator# 46901
city: Kanazawa
country: Japan
facility: Site Reference ID/Investigator# 46851
city: Kanazawa
country: Japan
facility: Site Reference ID/Investigator# 46852
city: Kawagoe
country: Japan
facility: Site Reference ID/Investigator# 46802
city: Kawasaki
country: Japan
facility: Site Reference ID/Investigator# 46900
city: Kirishima
country: Japan
facility: Site Reference ID/Investigator# 46875
city: Kitakyushu
country: Japan
facility: Site Reference ID/Investigator# 46870
city: Kumamoto
country: Japan
facility: Site Reference ID/Investigator# 46872
city: Kumamoto
country: Japan
facility: Site Reference ID/Investigator# 46912
city: Kyoto
country: Japan
facility: Site Reference ID/Investigator# 46864
city: Maebashi
country: Japan
facility: Site Reference ID/Investigator# 46943
city: Matsuyama
country: Japan
facility: Site Reference ID/Investigator# 46898
city: Miyazaki
country: Japan
facility: Site Reference ID/Investigator# 46915
city: Nagano
country: Japan
facility: Site Reference ID/Investigator# 46853
city: Nagano
country: Japan
facility: Site Reference ID/Investigator# 46855
city: Nagasaki
country: Japan
facility: Site Reference ID/Investigator# 46909
city: Nagasaki
country: Japan
facility: Site Reference ID/Investigator# 46910
city: Nagasaki
country: Japan
facility: Site Reference ID/Investigator# 46911
city: Nagoya
country: Japan
facility: Site Reference ID/Investigator# 46858
city: Nagoya
country: Japan
facility: Site Reference ID/Investigator# 46860
city: Nara
country: Japan
facility: Site Reference ID/Investigator# 46877
city: Nara
country: Japan
facility: Site Reference ID/Investigator# 46885
city: Niigata
country: Japan
facility: Site Reference ID/Investigator# 46848
city: Niigata
country: Japan
facility: Site Reference ID/Investigator# 46906
city: Oita
country: Japan
facility: Site Reference ID/Investigator# 46914
city: Okayama
country: Japan
facility: Site Reference ID/Investigator# 46869
city: Okayama
country: Japan
facility: Site Reference ID/Investigator# 46886
city: Okayama
country: Japan
facility: Site Reference ID/Investigator# 46887
city: Okayama
country: Japan
facility: Site Reference ID/Investigator# 46892
city: Okinawa
country: Japan
facility: Site Reference ID/Investigator# 46876
city: Osaka
country: Japan
facility: Site Reference ID/Investigator# 46946
city: Osaka
country: Japan
facility: Site Reference ID/Investigator# 46947
city: Rifu
country: Japan
facility: Site Reference ID/Investigator# 46842
city: Sagamihara
country: Japan
facility: Site Reference ID/Investigator# 46846
city: Saitama
country: Japan
facility: Site Reference ID/Investigator# 46803
city: Saitama
country: Japan
facility: Site Reference ID/Investigator# 46804
city: Saitama
country: Japan
facility: Site Reference ID/Investigator# 46878
city: Saitama
country: Japan
facility: Site Reference ID/Investigator# 46879
city: Sapporo
country: Japan
facility: Site Reference ID/Investigator# 46917
city: Shimotsuke
country: Japan
facility: Site Reference ID/Investigator# 46942
city: Shizuoka
country: Japan
facility: Site Reference ID/Investigator# 46854
city: Shizuoka
country: Japan
facility: Site Reference ID/Investigator# 46857
city: Shizuoka
country: Japan
facility: Site Reference ID/Investigator# 46859
city: Takamatsu
country: Japan
facility: Site Reference ID/Investigator# 46895
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46843
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46844
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46850
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46882
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46883
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46884
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46888
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46889
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46891
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 46896
city: Toyama
country: Japan
facility: Site Reference ID/Investigator# 46849
city: Toyama
country: Japan
facility: Site Reference ID/Investigator# 46907
city: Toyoake
country: Japan
facility: Site Reference ID/Investigator# 46862
city: Toyohashi
country: Japan
facility: Site Reference ID/Investigator# 46866
city: Tsukuba
country: Japan
facility: Site Reference ID/Investigator# 46926
city: Tsu
country: Japan
facility: Site Reference ID/Investigator# 46863
city: Yokohama
country: Japan
facility: Site Reference ID/Investigator# 46897
city: Yokohama
country: Japan
facility: Site Reference ID/Investigator# 46905
Study officials:
affiliation: Abbott Japan Co.,Ltd
name: Hiroshi Ukai, BS
role: STUDY_DIRECTOR
References:
citation: Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.
citation: Yamanaka H, Ishiguro N, Takeuchi T, Miyasaka N, Mukai M, Matsubara T, Uchida S, Akama H, Kupper H, Arora V, Tanaka Y. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial. Rheumatology (Oxford). 2014 May;53(5):904-13. doi: 10.1093/rheumatology/ket465. Epub 2014 Jan 17.