A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00870467
• Other study ID #: M06-859
• Status: Completed
• Phase: Phase 3
• First received: March 26, 2009
• Last updated: August 1, 2012
• Start date: March 2009
• Est. completion date: August 2011

Study information

• Verified date: August 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: August 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Double-blind adalimumab
Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)

Drug:
• Double-blind Placebo
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)

Biological:
• Open-label Adalimumab
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
• Open-labelAdalimumabRescue
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26

Locations

Country	Name	City	State
Japan	Site Reference ID/Investigator# 46861	Anjo
Japan	Site Reference ID/Investigator# 46919	Aomori
Japan	Site Reference ID/Investigator# 46805	Chiba
Japan	Site Reference ID/Investigator# 46806	Chiba
Japan	Site Reference ID/Investigator# 46880	Chiba
Japan	Site Reference ID/Investigator# 46881	Chiba
Japan	Site Reference ID/Investigator# 46890	Fuchu
Japan	Site Reference ID/Investigator# 46902	Fukuoka
Japan	Site Reference ID/Investigator# 46903	Fukuoka
Japan	Site Reference ID/Investigator# 46904	Fukuoka
Japan	Site Reference ID/Investigator# 46856	Gifu
Japan	Site Reference ID/Investigator# 46944	Gunma
Japan	Site Reference ID/Investigator# 46893	Hiroshima
Japan	Site Reference ID/Investigator# 46894	Hiroshima
Japan	Site Reference ID/Investigator# 12161	Hokkaido
Japan	Site Reference ID/Investigator# 46916	Hokkaido
Japan	Site Reference ID/Investigator# 46918	Hokkaido
Japan	Site Reference ID/Investigator# 46865	Hyogo
Japan	Site Reference ID/Investigator# 46871	Hyogo
Japan	Site Reference ID/Investigator# 46801	Ibaraki
Japan	Site Reference ID/Investigator# 46925	Ibaraki
Japan	Site Reference ID/Investigator# 46800	Iwate
Japan	Site Reference ID/Investigator# 46873	Kagoshima
Japan	Site Reference ID/Investigator# 46874	Kagoshima
Japan	Site Reference ID/Investigator# 46845	Kanagawa
Japan	Site Reference ID/Investigator# 46899	Kanagawa
Japan	Site Reference ID/Investigator# 46901	Kanagawa
Japan	Site Reference ID/Investigator# 46851	Kanazawa
Japan	Site Reference ID/Investigator# 46852	Kanazawa
Japan	Site Reference ID/Investigator# 46802	Kawagoe
Japan	Site Reference ID/Investigator# 46900	Kawasaki
Japan	Site Reference ID/Investigator# 46875	Kirishima
Japan	Site Reference ID/Investigator# 46870	Kitakyushu
Japan	Site Reference ID/Investigator# 46872	Kumamoto
Japan	Site Reference ID/Investigator# 46912	Kumamoto
Japan	Site Reference ID/Investigator# 46864	Kyoto
Japan	Site Reference ID/Investigator# 46943	Maebashi
Japan	Site Reference ID/Investigator# 46898	Matsuyama
Japan	Site Reference ID/Investigator# 46915	Miyazaki
Japan	Site Reference ID/Investigator# 46853	Nagano
Japan	Site Reference ID/Investigator# 46855	Nagano
Japan	Site Reference ID/Investigator# 46909	Nagasaki
Japan	Site Reference ID/Investigator# 46910	Nagasaki
Japan	Site Reference ID/Investigator# 46911	Nagasaki
Japan	Site Reference ID/Investigator# 46858	Nagoya
Japan	Site Reference ID/Investigator# 46860	Nagoya
Japan	Site Reference ID/Investigator# 46877	Nara
Japan	Site Reference ID/Investigator# 46885	Nara
Japan	Site Reference ID/Investigator# 46848	Niigata
Japan	Site Reference ID/Investigator# 46906	Niigata
Japan	Site Reference ID/Investigator# 46914	Oita
Japan	Site Reference ID/Investigator# 46869	Okayama
Japan	Site Reference ID/Investigator# 46886	Okayama
Japan	Site Reference ID/Investigator# 46887	Okayama
Japan	Site Reference ID/Investigator# 46892	Okayama
Japan	Site Reference ID/Investigator# 46876	Okinawa
Japan	Site Reference ID/Investigator# 46946	Osaka
Japan	Site Reference ID/Investigator# 46947	Osaka
Japan	Site Reference ID/Investigator# 46842	Rifu
Japan	Site Reference ID/Investigator# 46846	Sagamihara
Japan	Site Reference ID/Investigator# 46803	Saitama
Japan	Site Reference ID/Investigator# 46804	Saitama
Japan	Site Reference ID/Investigator# 46878	Saitama
Japan	Site Reference ID/Investigator# 46879	Saitama
Japan	Site Reference ID/Investigator# 46917	Sapporo
Japan	Site Reference ID/Investigator# 46942	Shimotsuke
Japan	Site Reference ID/Investigator# 46854	Shizuoka
Japan	Site Reference ID/Investigator# 46857	Shizuoka
Japan	Site Reference ID/Investigator# 46859	Shizuoka
Japan	Site Reference ID/Investigator# 46895	Takamatsu
Japan	Site Reference ID/Investigator# 46843	Tokyo
Japan	Site Reference ID/Investigator# 46844	Tokyo
Japan	Site Reference ID/Investigator# 46850	Tokyo
Japan	Site Reference ID/Investigator# 46882	Tokyo
Japan	Site Reference ID/Investigator# 46883	Tokyo
Japan	Site Reference ID/Investigator# 46884	Tokyo
Japan	Site Reference ID/Investigator# 46888	Tokyo
Japan	Site Reference ID/Investigator# 46889	Tokyo
Japan	Site Reference ID/Investigator# 46891	Tokyo
Japan	Site Reference ID/Investigator# 46896	Tokyo
Japan	Site Reference ID/Investigator# 46849	Toyama
Japan	Site Reference ID/Investigator# 46907	Toyama
Japan	Site Reference ID/Investigator# 46862	Toyoake
Japan	Site Reference ID/Investigator# 46866	Toyohashi
Japan	Site Reference ID/Investigator# 46863	Tsu
Japan	Site Reference ID/Investigator# 46926	Tsukuba
Japan	Site Reference ID/Investigator# 46897	Yokohama
Japan	Site Reference ID/Investigator# 46905	Yokohama

Sponsors (2)

Lead Sponsor	Collaborator
Abbott	Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Modified Total Sharp X-Ray Score at Week 26	Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.	Baseline, Week 26	No
Secondary	Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)	Patients were ACR20 responders if they had: >= 20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.	Week 26	No
Secondary	Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)	Patients were ACR50 responders if they had: >= 50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.	Week 26	No
Secondary	Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)	Patients were ACR70 responders if they had: >= 70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.	Week 26	No
Secondary	Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.	Baseline, Week 26	No
Secondary	Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.	Week 26	No
Secondary	Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26	Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of study drug. The number of participants who experienced any adverse event (serious or non-serious) while receiving double-blind study drug is summarized. See the Reported Adverse Event section for details.	Through Week 26	Yes
Secondary	Change From Baseline in Modified Total Sharp X-Ray Score at Week 52	Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS score (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates diseae progression; small positive/no change indicates slowing/halting of disease progression.	Baseline, Week 52	No
Secondary	Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)	Patients were ACR20 responders if they had: >=20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.	Week 52	No
Secondary	Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)	Patients were ACR50 responders if they had: >=50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.	Week 52	No
Secondary	Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)	Patients were ACR70 responders if they had: >=70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.	Week 52	No
Secondary	Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.	Baseline, Week 52	No
Secondary	Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.	Week 52	No
Secondary	Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52	Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of adalimumab. The number of participants who experienced any adverse event (serious or non-serious) while receiving any adalimumab during the study (double-blind adalimumab and/or open-label) is summarized. See the Reported Adverse Event section for details.	Through Week 52	Yes