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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01185301
Other study ID # M12-073
Secondary ID 2010-019514-24
Status Completed
Phase Phase 3
First received August 18, 2010
Last updated September 11, 2013
Start date October 2010
Est. completion date September 2012

Study information

Verified date September 2013
Source AbbVie
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationGermany: Paul-Ehrlich-InstitutCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsCanada: Health CanadaArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsSpain: Ministry of Health
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).


Recruitment information / eligibility

Status Completed
Enrollment 395
Est. completion date September 2012
Est. primary completion date September 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Male and female subjects at least 18 years of age

- Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider

- Subject must meet the following criteria:

1. Disease Activity Score of C-reactive Protein (DAS28[CRP]) = 3.2 (at the Baseline visit only)

2. At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)

3. At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)

4. C-reactive protein (CRP) = 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) = 28 mm/1h (at the Screening and Baseline visits)

5. Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive

- Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening

Exclusion Criteria:

- Subject has previous exposure to any systemic biologic therapy including adalimumab

- Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)

- Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)

- Subject has chronic arthritis diagnosed before age 17 years

- History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)

- Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test

- Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit

- Female subject who is pregnant or breast-feeding or considering becoming pregnant

Study Design

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


Intervention

Biological:
adalimumab
Pre-filled syringe every other week
Drug:
methotrexate
weekly oral capsule dosing

Locations

Country Name City State
Argentina Site Reference ID/Investigator# 44924 Buenos Aires
Argentina Site Reference ID/Investigator# 44926 Buenos Aires
Argentina Site Reference ID/Investigator# 44925 Rosario, Santa Fe
Argentina Site Reference ID/Investigator# 47302 San Juan
Austria Site Reference ID/Investigator# 44928 Graz
Austria Site Reference ID/Investigator# 44927 Vienna
Austria Site Reference ID/Investigator# 44930 Vienna
Belgium Site Reference ID/Investigator# 44934 Brussels
Belgium Site Reference ID/Investigator# 44935 Genk
Belgium Site Reference ID/Investigator# 44933 Gilly
Belgium Site Reference ID/Investigator# 44932 Liege
Canada Site Reference ID/Investigator# 43783 Edmonton
Canada Site Reference ID/Investigator# 43782 Winnipeg
Czech Republic Site Reference ID/Investigator# 44937 Brno
Czech Republic Site Reference ID/Investigator# 48962 Ceske Budejovice
Czech Republic Site Reference ID/Investigator# 44939 Ostrava
Czech Republic Site Reference ID/Investigator# 44936 Prague 2
Czech Republic Site Reference ID/Investigator# 44938 Uherske Hradiste
Czech Republic Site Reference ID/Investigator# 48963 Zlin
Germany Site Reference ID/Investigator# 44941 Berlin
Germany Site Reference ID/Investigator# 44945 Berlin-Buch
Germany Site Reference ID/Investigator# 44942 Munich
Germany Site Reference ID/Investigator# 44944 Ratingen
Germany Site Reference ID/Investigator# 44943 Zerbst
Poland Site Reference ID/Investigator# 44946 Bydgoszcz
Poland Site Reference ID/Investigator# 44982 Lodz
Poland Site Reference ID/Investigator# 46584 Torun
Poland Site Reference ID/Investigator# 44983 Warsaw
Poland Site Reference ID/Investigator# 44984 Warsaw
Puerto Rico Site Reference ID/Investigator# 38975 Caguas
Puerto Rico Site Reference ID/Investigator# 38916 San Juan
Puerto Rico Site Reference ID/Investigator# 39693 San Juan
Puerto Rico Site Reference ID/Investigator# 40122 San Juan
Puerto Rico Site Reference ID/Investigator# 39692 Vega Baja
Spain Site Reference ID/Investigator# 44947 A Coruna
Spain Site Reference ID/Investigator# 44987 Elche (Alicante)
Spain Site Reference ID/Investigator# 44948 Oviedo (Asturias)
Spain Site Reference ID/Investigator# 47782 Valencia
United States Site Reference ID/Investigator# 44284 Atlanta Georgia
United States Site Reference ID/Investigator# 41424 Bronx New York
United States Site Reference ID/Investigator# 38971 Charleston South Carolina
United States Site Reference ID/Investigator# 40651 Clifton New Jersey
United States Site Reference ID/Investigator# 42202 Columbus Ohio
United States Site Reference ID/Investigator# 39672 Covington Louisiana
United States Site Reference ID/Investigator# 39643 Dallas Texas
United States Site Reference ID/Investigator# 45325 Dallas Texas
United States Site Reference ID/Investigator# 41423 Duncansville Pennsylvania
United States Site Reference ID/Investigator# 41422 Freehold New Jersey
United States Site Reference ID/Investigator# 38907 Gainesville Georgia
United States Site Reference ID/Investigator# 40463 Greenville North Carolina
United States Site Reference ID/Investigator# 38912 Hemet California
United States Site Reference ID/Investigator# 52042 Houston Texas
United States Site Reference ID/Investigator# 38973 Huntsville Alabama
United States Site Reference ID/Investigator# 39666 Jackson Tennessee
United States Site Reference ID/Investigator# 38909 Jacksonville Florida
United States Site Reference ID/Investigator# 38972 Lawrenceville Georgia
United States Site Reference ID/Investigator# 45323 Little Rock Arkansas
United States Site Reference ID/Investigator# 41962 Mesa Arizona
United States Site Reference ID/Investigator# 40422 Miami Florida
United States Site Reference ID/Investigator# 44282 Norman Oklahoma
United States Site Reference ID/Investigator# 42204 Omaha Nebraska
United States Site Reference ID/Investigator# 39260 Phoenix Arizona
United States Site Reference ID/Investigator# 39670 Rock Island Illinois
United States Site Reference ID/Investigator# 38910 Sarasota Florida
United States Site Reference ID/Investigator# 40602 Seattle Washington
United States Site Reference ID/Investigator# 42282 Springfield Illinois
United States Site Reference ID/Investigator# 39673 Victorville California
United States Site Reference ID/Investigator# 38911 Wichita Kansas

Sponsors (1)

Lead Sponsor Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Canada,  Czech Republic,  Germany,  Poland,  Puerto Rico,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26 Percentage of participants achieving low disease activity as defined by a clinical response (DAS28[CRP] < 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. Week 26 No
Secondary Percentage of Participants With DAS28(CRP) Remission at Week 26 Disease remission was defined as a disease activity score, based on CRP, for 28 joints that was < 2.6 (DAS28[CRP] < 2.6). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. Week 26 No
Secondary Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26 Response, as defined by ACR 20 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: = 20% improvement in tender joint count; = 20% improvement in swollen joint count; and = 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Disability Index of the Health Assessment Questionnaire
Acute phase reactant value (C-reactive protein).
Baseline, Week 26 No
Secondary Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26 Response, as defined by ACR 50 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: = 50% improvement in tender joint count; = 50% improvement in swollen joint count; and = 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Disability Index of the Health Assessment Questionnaire
Acute phase reactant value (C-reactive protein).
Baseline, Week 26 No
Secondary Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26 Response, as defined by ACR 70 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: = 70% improvement in tender joint count; = 70% improvement in swollen joint count; and = 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Disability Index of the Health Assessment Questionnaire
Acute phase reactant value (C-reactive protein).
Baseline, Week 26 No
Secondary Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26 Response, as defined by ACR 90 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: = 90% improvement in tender joint count; = 90% improvement in swollen joint count; and = 90% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Disability Index of the Health Assessment Questionnaire
Acute phase reactant value (C-reactive protein).
Baseline, Week 26 No
Secondary Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26 Response, as defined by ACR 100 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: = 100% improvement in tender joint count; = 100% improvement in swollen joint count; and = 100% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Disability Index of the Health Assessment Questionnaire
Acute phase reactant value (C-reactive protein).
Baseline, Week 26 No
Secondary Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26 The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement. Baseline, Week 26 No
Secondary Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) = -0.22 at Week 26 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is a change from Baseline of = 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement. Baseline, Week 26 No
Secondary Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26 The modified Total Sharp Score (mTSS) is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. Baseline, Week 26 No
Secondary Percentage of Participants With No Radiographic Progression at Week 26 "No radiographic progression" was defined as a change from Baseline in modified Total Sharp Score (mTSS) at Week 26 of = 0.5. mTSS is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. Baseline, Week 26 No
Secondary Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26 SDAI is a measure of disease activity derived as follows: SDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) + CRP (mg/dL), where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]), and CRP is C-reactive protein measured in mg/dL. SDAI total score = 0 to 86. SDAI = 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. Week 26 No
Secondary Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26 CDAI is a measure of disease activity derived as follows: CDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]). CDAI total score = 0 to 76. CDAI = 2.8 indicates disease remission, > 2.8 to 10 = low disease activity, > 10 to 22 = moderate disease activity, and > 22 = high disease activity. Week 26 No
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