Study Evaluating the Efficacy and Safety of Etanercept and Methotrexate in Japanese Subjects With Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

Official title:

A Randomized, Double-Blind, Multicenter, Comparative Study Evaluating the Efficacy and Safety of Etanercept and Methotrexate in Japanese Subjects With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445770
• Other study ID #: 0881A1-315
• Secondary ID: B1801002
• Status: Completed
• Phase: Phase 3
• First received: March 8, 2007
• Last updated: August 10, 2011
• Start date: July 2006
• Est. completion date: July 2010

Study information

• Verified date: August 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the effects of etanercept (10 mg and 25 mg) compared with methotrexate (up to 8 mg per week) on the slowing of joint destruction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 550
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Must be Japanese and live in Japan

• Must be age 20 to 75 years

• Diagnosed less than or equal to 10 years from time of first visit

Exclusion Criteria:

• Anyone who has received etanercept or TNF-inhibitors such as infliximab or adalimumab in the past

• Patient with other rheumatic diseases or conditions that could predispose the patient to infection

• Pregnant or lactating women

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Etanercept
10 mg twice weekly, subcutaneous injection for 52 weeks
• Etanercept
25 mg, twice weekly, subcutaneous injection for 52 weeks
• Methotrexate
up to 8 mg per week, oral dosing for 52 weeks

Locations

Country	Name	City	State
Japan	Pfizer Investigational Site	Asahi	Chiba
Japan	Pfizer Investigational Site	Asahikawa	Hokkaido
Japan	Pfizer Investigational Site	Bunkyo-ku	Tokyo
Japan	Pfizer Investigational Site	Fukui
Japan	Pfizer Investigational Site	Fukuoka
Japan	Pfizer Investigational Site	Fukuoka
Japan	Pfizer Investigational Site	Fukuoka
Japan	Pfizer Investigational Site	Goshogawara	Aomori
Japan	Pfizer Investigational Site	Hiroshima
Japan	Pfizer Investigational Site	Hyuga	Miyazaki
Japan	Pfizer Investigational Site	Iizuka	Fukuoka
Japan	Pfizer Investigational Site	Ikoma	Nara
Japan	Pfizer Investigational Site	Kagoshima
Japan	Pfizer Investigational Site	Kagoshima
Japan	Pfizer Investigational Site	Kakogawa	Hyogo
Japan	Pfizer Investigational Site	Kato city Fujita letter Higashiyama
Japan	Pfizer Investigational Site	Katoh	Hyougo
Japan	Pfizer Investigational Site	Kawagoe	Saitama
Japan	Pfizer Investigational Site	Kawasaki	Kanagawa
Japan	Pfizer Investigational Site	Komatsu	Ishikawa
Japan	Pfizer Investigational Site	Kumamoto
Japan	Pfizer Investigational Site	Kumamoto
Japan	Pfizer Investigational Site	Kurume	Fukuoka
Japan	Pfizer Investigational Site	Kurume	Fukuoka
Japan	Pfizer Investigational Site	Matsuyama	Ehime
Japan	Pfizer Investigational Site	Miyagi
Japan	Pfizer Investigational Site	Miyazaki
Japan	Pfizer Investigational Site	Munakata	Fukuoka
Japan	Pfizer Investigational Site	Nagoya	Aichi
Japan	Pfizer Investigational Site	Nagoya	Aichi
Japan	Pfizer Investigational Site	Ota	Tokyo
Japan	Pfizer Investigational Site	Sagamihara	Kanagawa
Japan	Pfizer Investigational Site	Sapporo	Hokkaido
Japan	Pfizer Investigational Site	Sasebo	Nagasaki
Japan	Pfizer Investigational Site	Sendai	Miyagi
Japan	Pfizer Investigational Site	Sumida-ku	Tokyo
Japan	Pfizer Investigational Site	Takasaki	Gunma
Japan	Pfizer Investigational Site	Tokorozawa	Saitama
Japan	Pfizer Investigational Site	Toyama
Japan	Pfizer Investigational Site	Yokohama	Kanagawa
Japan	Pfizer Investigational Site	Yuki	Ibaraki

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52	mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation 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 represents improvement.	Week 52	No
Secondary	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24	mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation 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 represents improvement.	Week 24	No
Secondary	Change From Baseline in Erosion Score at Weeks 24 and 52	Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. Change = score at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline, Week 24, and Week 52	No
Secondary	Change From Baseline in Joint Space Narrowing (JSN) Score at Weeks 24 and 52	JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline, Week 24, and Week 52	No
Secondary	Percentage of Participants With no Progression of Joint Destruction at Week 52	Absence of joint destruction defined by 3 categories (mTSS change <=0.5, <=3.0, and	Baseline and Week 52	No
Secondary	Change From Baseline in Swollen Joint Count at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	American College of Rheumatology (ACR) swollen joint count was an assessment of 68 joints. Joints classified as either swollen or not swollen. Change = scores at observation minus score at Baseline, and total possible scores ranged from -68 to 68. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Number of Painful Joints on Pressure or on Motion at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	71 joints assessed by the investigator using criteria based on pressure and joint manipulation. Change = scores at observation minus score at Baseline, and total possible scores ranged from -71 to 71. An increase in tender joint count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Physician's Global Assessment of Symptoms at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	Physician Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Patient's Global Assessment at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	Patient's Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Mean Duration of Morning Stiffness at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement. Change = scores at observation minus score at Baseline. An increase in stiffness duration from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	100 millimeter (mm) line (VAS) marked by participant. Intensity of pain range (over past week): 0mm = no pain to 100mm = worst possible pain. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in VAS for Participant General Health at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	100mm line (VAS) marked by participant. Participants asked, "In general how would you rate your health over the last 2-3 weeks?" 0mm=very well to 100mm=extremely bad. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Change = scores at observation minus score at Baseline and total possible scores ranged from -3 to 3. An increase in score from baseline represented disease progression and/or joint worsening and a decrease represented improvement.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response	ACR20 response: greater than or equal to (=) 20 percent (%) improvement in tender joint count; = 20% improvement in swollen joint count; and = 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Percentage of Participants With an ACR50 Response	ACR50 response: = 50% improvement in tender joint count; = 50% improvement in swollen joint count; and = 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Percentage of Participants With an ACR70 Response	ACR70 response: = 70% improvement in tender joint count; = 70% improvement in swollen joint count; and = 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Disease Activity Score (DAS) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	DAS: weighted calculation of joint tenderness score (Ritchie Articular Index[RAI]), swollen joint count of 44 joints, natural logarithm (ln) of erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using VAS. RAI defined as sum of 26 possible 0 to 3 tender scores. DAS = 0.53938 square root (v) (RAI) + 0.06465 (swollen joint count) + 0.330 (ln ESR) + 0.00722 (GH). Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Disease Activity Score in 28 Joints (DAS28) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	DAS based on 28 painful joint counts, 28 swollen joint counts, ESR, and GH. DAS28 score calculated as 0.56 v (28 painful joint count) + 0.28 v (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH. Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	CRP: marker of inflammation. Higher level consistent with inflammation. Normal CRP range: 0 to 1.0 milligrams per deciliter (mg/dL).	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No
Secondary	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	ESR: laboratory test that provided a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/hour. Normal range: 0-30mm/h. Higher rate consistent with inflammation.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	No

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