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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00420927




Registration number
NCT00420927
Ethics application status
Date submitted
9/01/2007
Date registered
11/01/2007
Date last updated
18/04/2012

Titles & IDs
Public title
Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
Scientific title
A Multicenter, Randomized, Double-Period, Double - Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)
Secondary ID [1] 0 0
2006-004139-31
Secondary ID [2] 0 0
M06-810
Universal Trial Number (UTN)
Trial acronym
OPTIMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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
Treatment: Other - adalimumab
Treatment: Drugs - methotrexate
Treatment: Other - placebo

Experimental: ADA+MTX/PBO+MTX (Arm 1) - Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2

Experimental: ADA+MTX/ADA+MTX (Arm2) - Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2

Experimental: ADA+MTX/OL ADA+MTX (Arm 3) - Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2

Experimental: PBO+MTX/PBO+MTX (Arm 4) - Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2

Experimental: PBO+MTX/OL ADA+MTX (Arm 5) - Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.


Treatment: Other: adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)

Treatment: Drugs: methotrexate
Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.

Treatment: Other: placebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4
Timepoint [1] 0 0
Week 78
Secondary outcome [1] 0 0
Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1
Timepoint [1] 0 0
Week 78
Secondary outcome [2] 0 0
Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78
Timepoint [2] 0 0
Week 78
Secondary outcome [3] 0 0
Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78
Timepoint [3] 0 0
Week 78
Secondary outcome [4] 0 0
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78
Timepoint [4] 0 0
Week 78
Secondary outcome [5] 0 0
Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78
Timepoint [5] 0 0
Week 78
Secondary outcome [6] 0 0
Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78
Timepoint [6] 0 0
Week 78
Secondary outcome [7] 0 0
Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78
Timepoint [7] 0 0
Week 78
Secondary outcome [8] 0 0
Change From Baseline in DAS28 Score at Week 78
Timepoint [8] 0 0
Baseline to Week 78
Secondary outcome [9] 0 0
Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78
Timepoint [9] 0 0
Week 78
Secondary outcome [10] 0 0
Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78
Timepoint [10] 0 0
Week 78
Secondary outcome [11] 0 0
Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78
Timepoint [11] 0 0
Week 78
Secondary outcome [12] 0 0
Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78
Timepoint [12] 0 0
Week 78
Secondary outcome [13] 0 0
Change From Baseline in CDAI Score at Week 78
Timepoint [13] 0 0
Baseline to Week 78
Secondary outcome [14] 0 0
Change From Baseline in SDAI Score at Week 78
Timepoint [14] 0 0
Baseline to Week 78
Secondary outcome [15] 0 0
Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78
Timepoint [15] 0 0
Baseline to Week 78
Secondary outcome [16] 0 0
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78
Timepoint [16] 0 0
Week 78
Secondary outcome [17] 0 0
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78
Timepoint [17] 0 0
Week 78
Secondary outcome [18] 0 0
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78
Timepoint [18] 0 0
Week 78

Eligibility
Key inclusion criteria
Inclusion Criteria

* Subject must be 18 or older and in good health
* Subject must meet the definition of early rheumatoid arthritis (RA) defined by the 1987-revised American College of Rheumatology (ACR) classification criteria and had disease duration of less than 1 year from diagnosis
* Subject must have a Disease Activity Score (DAS28, based on C-reactive protein) greater than 3.2, at least 6 swollen joints out of the 66 assessed, and at least 8 tender joints out of the 68 assessed
* Subject must fulfill at least one of the following three criteria:

* Rheumatoid factor positive
* Greater than 1 joint erosion
* Anti-cyclic citrullinated peptide (CCP) antibody positive.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Subject has previously received systemic anti-tumor necrosis factor (TNF) therapy
* Subject has received any biologic or investigational therapy within 6 weeks prior to Baseline
* Subject has been previously treated with more than 2 disease-modifying antirheumatic drugs (DMARDs) or MTX, had been treated with intra-articular or parenteral administration of corticosteroids in preceding 4 weeks, or had undergone joint surgery within the preceding 2 months at joints to be assessed during the study.

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 4
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
1/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2010
Sample size
Target
Accrual to date
Final
1032
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site Reference ID/Investigator# 8380 - Campsie, Sydney
Recruitment hospital [2] 0 0
Site Reference ID/Investigator# 6954 - Clayton
Recruitment hospital [3] 0 0
Site Reference ID/Investigator# 6940 - Malvern East
Recruitment postcode(s) [1] 0 0
2194 - Campsie, Sydney
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3145 - Malvern East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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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
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Florida
Country [5] 0 0
United States of America
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Idaho
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United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Maryland
Country [9] 0 0
United States of America
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Massachusetts
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United States of America
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New Hampshire
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New Jersey
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New Mexico
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New York
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Washington
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Wisconsin
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Argentina
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Buenos Aires
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Argentina
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Quilmes
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Argentina
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San Miguel de Tucuman
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Austria
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Graz
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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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Genk
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Belgium
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Gilly
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Belgium
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Liege
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Belgium
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Mechelen
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Belgium
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Sint-Niklaas
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Belgium
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Yvoir
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Burlington
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Edmonton
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Halifax
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Hamilton
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Montreal
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Ottawa
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Richmond
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Sainte-Foy, Quebec
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Sarnia
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Victoria
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Halle
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Zerbst
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Auckland 6
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Timaru
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Wellington
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Alesund
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Kristiansand S
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Levanger
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Lillehammer
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Trondheim
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Katowice
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Lublin
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Caguas
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Puerto Rico
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Ponce
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Puerto Rico
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San Juan
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Slovakia
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Piestany
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South Africa
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Berea, Durban
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South Africa
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Cape Town
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South Africa
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Port Elizabeth
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South Africa
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Pretoria
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South Africa
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Soweto
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Spain
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A Coruna
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Spain
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Bilbao
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Spain
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Elche (Alicante)
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Spain
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Madrid
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Spain
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Oviedo
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Spain
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Santiago de Compostela
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Spain
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Zaragoza
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Sweden
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Eskilstuna
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Sweden
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Falun
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Sweden
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Malmoe
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Sweden
State/province [110] 0 0
Stockholm
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Sweden
State/province [111] 0 0
Uppsala
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United Kingdom
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Bath
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United Kingdom
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Huddersfield
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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
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United Kingdom
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Oxford
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United Kingdom
State/province [118] 0 0
Southampton
Country [119] 0 0
United Kingdom
State/province [119] 0 0
York

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Abbott
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study compared the safety and efficacy of combination therapy with adalimumab plus methotrexate (MTX) to that of MTX monotherapy (i.e., placebo plus MTX) in subjects with early rheumatoid arthritis (RA).
Trial website
https://clinicaltrials.gov/study/NCT00420927
Trial related presentations / publications
Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.
Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018 Nov;77(11):1566-1572. doi: 10.1136/annrheumdis-2018-213502. Epub 2018 Aug 3.
Kavanaugh A, van Vollenhoven RF, Fleischmann R, Emery P, Sainsbury I, Florentinus S, Chen S, Guerette B, Kupper H, Smolen JS. Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis. Ann Rheum Dis. 2018 Feb;77(2):289-292. doi: 10.1136/annrheumdis-2017-211871. Epub 2017 Nov 16.
Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.
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.
Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, Guerette B, Kupper H, Redden L, Arora V, Kavanaugh A. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014 Jan 25;383(9914):321-32. doi: 10.1016/S0140-6736(13)61751-1. Epub 2013 Oct 26. Erratum In: Lancet. 2014 Jan 25;383(9914):308.
Public notes

Contacts
Principal investigator
Name 0 0
Laura Redden, MD, PhD
Address 0 0
Abbott
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00420927