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

UCB

Status and phase: Completed; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Biological: Certolizumab Pegol (CZP); Drug: Methotrexate (MTX); Biological: Adalimumab (ADA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01500278

2011-002067-20 (EudraCT Number)

RA0077

Details and patient eligibility

About

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.

Enrollment: 915 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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915 participants in 4 patient groups

Certolizumab Pegol + Methotrexate (CZP + MTX)

Active Comparator group

Treatment:

Drug: Methotrexate (MTX)

Biological: Certolizumab Pegol (CZP)

Adalimumab + Methotrexate (ADA + MTX)

Active Comparator group

Treatment:

Drug: Methotrexate (MTX)

Biological: Adalimumab (ADA)

CZP + MTX followed by ADA + MTX

Active Comparator group

Description:

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.

Treatment:

Drug: Methotrexate (MTX)

Biological: Certolizumab Pegol (CZP)

Biological: Adalimumab (ADA)

ADA + MTX followed by CZP + MTX

Active Comparator group

Description:

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:

Drug: Methotrexate (MTX)

Biological: Certolizumab Pegol (CZP)

Biological: Adalimumab (ADA)