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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00195663




Registration number
NCT00195663
Ethics application status
Date submitted
13/09/2005
Date registered
20/09/2005
Date last updated
12/07/2013

Titles & IDs
Public title
Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis
Scientific title
A Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFa Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER).
Secondary ID [1] 0 0
DE013
Universal Trial Number (UTN)
Trial acronym
PREMIER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Adalimumab - Participants received adalimumab 40 mg subcutaneous injection once every other week and placebo to methotrexate orally once a week during the 2-year double-blind treatment phase and then adalimumab 40 mg every other week for up to 8 years in the open-label extension.

Experimental: Adalimumab + methotrexate - Participants received adalimumab 40 mg subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.

Experimental: Methotrexate - Participants received placebo to adalimumab subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52
Timepoint [1] 0 0
Baseline and 52 Weeks
Primary outcome [2] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Timepoint [2] 0 0
Baseline and Week 52
Secondary outcome [1] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [2] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 104
Timepoint [2] 0 0
Baseline and Week 104
Secondary outcome [3] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 104
Timepoint [3] 0 0
Baseline and Week 104
Secondary outcome [4] 0 0
Number of Participants Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at Week 52
Timepoint [4] 0 0
Week 52
Secondary outcome [5] 0 0
Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36) at Week 52
Timepoint [5] 0 0
Baseline and Week 52
Secondary outcome [6] 0 0
Number of Participants With Major Clinical Response After 104 Weeks of Treatment
Timepoint [6] 0 0
Any 6 continuous months from Baseline to Week 104
Secondary outcome [7] 0 0
Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36) at Week 52
Timepoint [7] 0 0
Baseline and Week 52
Secondary outcome [8] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Weeks 26 and 76
Timepoint [8] 0 0
Baseline and Weeks 26 and 76
Secondary outcome [9] 0 0
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria During the Double-blind Phase
Timepoint [9] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [10] 0 0
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria During the Double-blind Phase
Timepoint [10] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [11] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase
Timepoint [11] 0 0
Baseline and Weeks 12, 26, 76, and 104
Secondary outcome [12] 0 0
Number of Participants With Improvement in the HAQ-DI Score = 0.3 During the Double-blind Treatment Phase
Timepoint [12] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [13] 0 0
Change From Baseline in Health Utilities Index Mark 2 and Mark 3 (HUI 2/3) During the Double-blind Treatment Phase
Timepoint [13] 0 0
Baseline and Weeks 26, 52, and 104
Secondary outcome [14] 0 0
Change From Baseline in the Short Form-36 Health Status Survey (SF-36) During the Double-blind Treatment Phase
Timepoint [14] 0 0
Baseline and Weeks 26 and 104
Secondary outcome [15] 0 0
Numeric American College of Rheumatology (ACR-N) During the Double-blind Treatment Phase
Timepoint [15] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [16] 0 0
Change From Baseline in Disease Activity Score (DAS28) During the Double-blind Treatment Phase
Timepoint [16] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [17] 0 0
Change From Baseline in Joint Erosion Score During the Double-blind Treatment Period
Timepoint [17] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [18] 0 0
Change From Baseline in Joint Space Narrowing Score During the Double-blind Treatment Period
Timepoint [18] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [19] 0 0
Number of Participants With No Worsening in Modified Total Sharp Score or Components During the Double-blind Treatment Phase
Timepoint [19] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [20] 0 0
Number of Participants With No Erosions at Baseline and No New Erosions at Weeks 52 and 104
Timepoint [20] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [21] 0 0
Number of Participants With Non-Involved Joints at Baseline and No Newly Involved Joints at Weeks 52 and 104
Timepoint [21] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [22] 0 0
Number of Participants Meeting ACR20 Response Criteria Over 10 Years by Adalimumab Exposure
Timepoint [22] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [23] 0 0
Number of Participants Meeting ACR50 Response Criteria Over 10 Years by Adalimumab Exposure
Timepoint [23] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [24] 0 0
Number of Participants Meeting ACR70 Response Criteria Over 10 Years by Adalimumab Exposure
Timepoint [24] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [25] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure
Timepoint [25] 0 0
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
Secondary outcome [26] 0 0
Change From Baseline in DAS28 Over 10 Years by Adalimumab Exposure
Timepoint [26] 0 0
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
Secondary outcome [27] 0 0
Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by Adalimumab Exposure
Timepoint [27] 0 0
After 1, 2, 5, and 10 years of adalimumab exposure
Secondary outcome [28] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) Over 10 Years
Timepoint [28] 0 0
Baseline (prior to first study drug treatment) and Years 2 and 10
Secondary outcome [29] 0 0
Number of Participants With No Radiographic Progression Over 10 Years
Timepoint [29] 0 0
Baseline (prior to first study drug treatment) and Years 2 and 10.
Secondary outcome [30] 0 0
Composite Score of ACR50 Plus No Change in Modified Total Sharp Score
Timepoint [30] 0 0
Year 10
Secondary outcome [31] 0 0
Number of Participants With a Major Clinical Response Over 10 Years by Adalimumab Exposure
Timepoint [31] 0 0
From the first dose of adalimumab (at Week 1 or Week 106 for patients initially randomized to methotrexate in the DB phase) to Year 10
Secondary outcome [32] 0 0
Number of Participants With Improvement in HAQ-DI by 0.22 and 0.5 Units Over 10 Years by Adalimumab Exposure
Timepoint [32] 0 0
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.

Eligibility
Key inclusion criteria
* Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
* Diagnosis of rheumatoid arthritis (RA) as defined by the 1987-revised American College of Rheumatology (ACR) criteria, with a disease duration less than 3 years, at least 8 swollen joints out of the 66 joints assessed, at least 10 tender joints out of the 68 joints assessed, at least 1 joint erosion or rheumatoid factor (RF) positivity, erythrocyte sedimentation rate (ESR) >= 28 mm/1h or C-reactive protein (CRP) >= 1.5 mg/dl
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Chronic arthritis diagnosed before the age of 16
* Preceding treatment with MTX, cyclophosphamide, cyclosporin, azathioprine or more than 2 other disease-modifying anti-rheumatic drugs (DMARDs)
* Subject previously received anti-tumor necrosis factor (TNF) therapy
* Permanently wheelchair-bound or bedridden patients
* Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
* Female subject who is pregnant or breast-feeding or considering becoming pregnant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site Reference ID/Investigator# 310 - Brisbane
Recruitment hospital [2] 0 0
Site Reference ID/Investigator# 755 - Camperdown
Recruitment hospital [3] 0 0
Site Reference ID/Investigator# 337 - Clayton
Recruitment hospital [4] 0 0
Site Reference ID/Investigator# 331 - Darlinghurst, Sydney
Recruitment hospital [5] 0 0
Site Reference ID/Investigator# 745 - Kogarah
Recruitment hospital [6] 0 0
Site Reference ID/Investigator# 738 - Maroochydore
Recruitment hospital [7] 0 0
Site Reference ID/Investigator# 335 - New Lambton
Recruitment hospital [8] 0 0
Site Reference ID/Investigator# 737 - Shenton Park
Recruitment hospital [9] 0 0
Site Reference ID/Investigator# 307 - South Hobart
Recruitment hospital [10] 0 0
Site Reference ID/Investigator# 427 - West Heidelberg
Recruitment hospital [11] 0 0
Site Reference ID/Investigator# 739 - Woodville
Recruitment postcode(s) [1] 0 0
4102 - Brisbane
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
4558 - Maroochydore
Recruitment postcode(s) [7] 0 0
2305 - New Lambton
Recruitment postcode(s) [8] 0 0
6008 - Shenton Park
Recruitment postcode(s) [9] 0 0
7004 - South Hobart
Recruitment postcode(s) [10] 0 0
3081 - West Heidelberg
Recruitment postcode(s) [11] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New Hampshire
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
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Austria
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Vienna
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Belgium
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Brussels
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Belgium
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Diepenbeek
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Belgium
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Ghent
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Belgium
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Leuven
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Belgium
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Liege
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Canada
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Ontario
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Canada
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Edmonton
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Canada
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Hamilton
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Montreal
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Newmarket
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Pointe-Claire
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Richmond
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St. John's
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Toronto
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Victoria
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Winnipeg
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Czech Republic
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Hradec Kralove
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Czech Republic
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Plzen
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Czech Republic
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Prague 2
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Denmark
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Grasten
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Finland
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Heinola
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Helsinki
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Pierre Benite
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Berlin
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Erlangen
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Freiburg
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Munich
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Ratingen
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Vogelsang-Gommern
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Ireland
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Cork
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Ireland
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Dublin 4
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Italy
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Genoa
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Italy
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Naples
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Italy
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Udine
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Italy
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Verona
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Groningen
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Leiden
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Netherlands
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Maastricht
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Netherlands
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Nijmegen
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Norway
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Osla
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Slovakia
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Piestany
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Guadalajara
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Madrid
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Spain
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Santiago de Compostela
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Spain
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Sevilla
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Sweden
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Stockholm
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Sweden
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Umea
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Uppsala
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Sweden
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Vasteras
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Switzerland
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Lausanne
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United Kingdom
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Bangor
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United Kingdom
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Cambridge
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United Kingdom
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Hereford
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie (prior sponsor, Abbott)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dawn Carlson
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.