A Study to Compare Efficacy, Pharmacokinetics, Safety and Immunogenicity of MB04 [proposed Etanercept Biosimilar] to Enbrel® [EU-sourced] in Rheumatoid Arthritis

A Prospective, Randomized, Double-blind, Parallel-group Study to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of MB04 and EU-sourced Enbrel® in Patients with Moderate to Severe Rheumatoid Arthritis

A study to compare efficacy, pharmacokinetics, safety and immunogenicity of MB04 [proposed etanercept biosimilar] to Enbrel® [EU-sourced] in rheumatoid arthritis

The study will randomize approximately 458 patients aged between 18 and 75 years with active Rheumatoid Arthritis despite methotrexate therapy.

All patients shall receive methotrexate for ≥12 weeks and on a stable dose (10 to 25 mg/week) for ≥8 weeks prior to randomization, and folic acid (≥5 mg/week) from 4 weeks prior to screening until the end of the treatment period (Week 36).

Screening evaluations will be completed within 28 days prior to randomization. There will be 2 periods in the study: Main Treatment period and Transition period.

During the Main Treatment Period, eligible patients will be randomized, at a 1:1 ratio, to administer a 50 mg weekly dose of MB04 or EU- sourced Enbrel® subcutaneously (SC) using an Interactive Response System (IRT). After completing Week 24 assessment, patients will continue to receive the study treatment up to Week 36. Those patients who were originally assigned to EU-sourced Enbrel® will be randomized, at a 1:1 ratio, to receive either MB04 or EU-sourced Enbrel® SC, while patients originally assigned to MB04 will continue with the same treatment until Week 36.

After treatment discontinuation, patients will undergo a Safety follow-up period for 4 weeks, up to week 40.

Inclusion

• Documented history of RA diagnosis consistent with the 2010 ACR/EULAR classification criteria ≥6 months prior to randomization (but not exceeding 15 years prior to screening).
• Moderately to severe RA despite appropriate MTX at baseline therapy defined as having more than or equal to six swollen joints and more than or equal to six tender joints and either erythrocyte sedimentation rate (ESR, Westergren) ≥ 28 mm/h or serum C-reactive protein > 5.0 mg/dL and positive rheumatoid factor and/or CCP at screening
• Stable dose MTX between 10 to 25 mg weekly during ≥12 weeks, since ≥8 weeks prior to randomization
• Stable dose of NSAID and /or other analgesics for at least 4 weeks prior to randomization, when used
• Stable dose ≤10 mg prednisone daily or equivalent for ≥4 weeks prior to randomization, when used
• Patients who are otherwise medically stable according to investigator's discretion
• Agree to use highly effective contraceptive methods up to 6 months after las dose Exclusion
• Previously treated with any biologic or targeted synthetic DMARD
• Previously treated with any monoclonal antibody for other condition than RA
• Hypersensitivity to any component of study drug and/or prefilled syringe components
• Arthritis with onset prior to age 16 years or current diagnosis of inflammatory joint disease other than RA
• Systemic manifestations of RA other that rheumatoid nodules or secondary Sjogren's syndrome
• Active infection or potentially relapsing infections that could have a severe outcome. Latent tuberculosis infection detected during screening should start an approved treatment regimen according to standard of care and rescreened
• Solid or hematologic malignancy within the past 5 years
• Pregnant and breastfeeding women
• Any medical condition in the opinion of the investigator that would be a risk for safety, cooperation in the study or interferes with the interpretation of the study results