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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01500278




Registration number
NCT01500278
Ethics application status
Date submitted
22/12/2011
Date registered
28/12/2011
Date last updated
31/07/2018

Titles & IDs
Public title
Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate
Scientific title
A Multicenter, Single-blind, Randomized Parallel-group Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis Responding Inadequately to Methotrexate
Secondary ID [1] 0 0
2011-002067-20
Secondary ID [2] 0 0
RA0077
Universal Trial Number (UTN)
Trial acronym
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(has expanded access)
Description of intervention(s) / exposure
Treatment: Other - Certolizumab Pegol (CZP)
Treatment: Other - Adalimumab (ADA)
Treatment: Drugs - Methotrexate (MTX)

Active comparator: Certolizumab Pegol + Methotrexate (CZP + MTX) -

Active comparator: Adalimumab + Methotrexate (ADA + MTX) -

Active comparator: CZP + MTX followed by ADA + MTX - Those subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.

Active comparator: ADA + MTX followed by CZP + MTX - Those subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.


Treatment: Other: Certolizumab Pegol (CZP)
* Active substance: an injectable volume of 1 ml solution for injection CZP
* Pharmaceutical form: prefilled syringes CZP
* Concentration: 200 mg/ml CZP
* Route of Administration: injections will be given subcutaneously: loading dose of CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal.

Treatment: Other: Adalimumab (ADA)
* Active substance: an injectable volume of 0.8 ml solution for injection ADA
* Pharmaceutical form: prefilled syringes ADA
* Concentration: 40 mg/0.8 ml ADA
* Route of Administration: injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal.

Treatment: Drugs: Methotrexate (MTX)
* Active substance: Methotrexate
* Pharmaceutical form: oral tablet
* Concentration: 15-25 mg/week
* Route of Administration: MTX orally
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
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
Timepoint [1] 0 0
Week 12
Primary outcome [2] 0 0
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104
Timepoint [2] 0 0
Week 104
Secondary outcome [1] 0 0
Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104
Timepoint [1] 0 0
Week 104
Secondary outcome [2] 0 0
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6
Timepoint [2] 0 0
Week 6
Secondary outcome [3] 0 0
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 6
Timepoint [3] 0 0
Week 6
Secondary outcome [4] 0 0
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12
Timepoint [5] 0 0
Week 104
Secondary outcome [6] 0 0
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104
Timepoint [6] 0 0
From Baseline to Week 104
Secondary outcome [7] 0 0
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12
Timepoint [7] 0 0
From Week 12 up to Week 104

Eligibility
Key inclusion criteria
* Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aletaha D et al, 2010)
* Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening
* Subject must have moderate to severe RA disease at Screening and Baseline defined as:

1. Screening (all criteria required)

* = 4 swollen joints (of 28 prespecified joints)
* Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
* C-Reactive Protein (CRP) concentration = 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) = 28 mm/hr
2. Baseline (both criteria required)

* = 4 swollen joints (of 28 prespecified joints)
* Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
* Subject must have inadequately responded previously to Methotrexate (MTX)
* Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase
* Diagnosis of any other inflammatory arthritis
* Infected with Tuberculosis (TB) or high risk of acquiring TB infection
* Subjects with concurrent acute or chronic viral hepatitis B or C infection
* Subjects with a history of chronic or recurrent infections or subjects at high risk of infection
* Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid

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 assessing the outcomes
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
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2016
Sample size
Target
Accrual to date
Final
915
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
6 - Camperdown
Recruitment hospital [2] 0 0
5 - Kogarah
Recruitment hospital [3] 0 0
2 - Maroochydore
Recruitment hospital [4] 0 0
4 - Hobart
Recruitment hospital [5] 0 0
7 - Clayton
Recruitment hospital [6] 0 0
8 - Fitzroy
Recruitment hospital [7] 0 0
1 - Malvern
Recruitment hospital [8] 0 0
3 - Subiaco
Recruitment postcode(s) [1] 0 0
- Camperdown
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- Kogarah
Recruitment postcode(s) [3] 0 0
- Maroochydore
Recruitment postcode(s) [4] 0 0
- Hobart
Recruitment postcode(s) [5] 0 0
- Clayton
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- Fitzroy
Recruitment postcode(s) [7] 0 0
- Malvern
Recruitment postcode(s) [8] 0 0
- Subiaco
Recruitment outside Australia
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Porto
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Iasi
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A Coruna
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Madrid
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Sabadell
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Vigo
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Zürich
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Ashford
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Brighton
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Leeds
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London
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Poole
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Sheffield
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Upton
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United Kingdom
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Wigan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
UCB Pharma SA
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Parexel
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.
Trial website
https://clinicaltrials.gov/study/NCT01500278
Trial related presentations / publications
Smolen JS, Burmester GR, Combe B, Curtis JR, Hall S, Haraoui B, van Vollenhoven R, Cioffi C, Ecoffet C, Gervitz L, Ionescu L, Peterson L, Fleischmann R. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study. Lancet. 2016 Dec 3;388(10061):2763-2774. doi: 10.1016/S0140-6736(16)31651-8. Epub 2016 Nov 15. Erratum In: Lancet. 2017 Feb 4;389(10068):e2. doi: 10.1016/S0140-6736(17)30145-9.
Paul S, Marotte H, Kavanaugh A, Goupille P, Kvien TK, de Longueville M, Mulleman D, Sandborn WJ, Vande Casteele N. Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis. Clin Transl Sci. 2020 Jul;13(4):743-751. doi: 10.1111/cts.12760. Epub 2020 Apr 1.
Public notes

Contacts
Principal investigator
Name 0 0
UCB Cares
Address 0 0
+1 877 822 9493 (UCB)
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/NCT01500278