Study to Demonstrate Non-Inferior Efficacy and Safety of CinnoRA® Versus Humira® for Treatment of Active RA
Condition: Active Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Adalimumab; Methotrexate; Folic Acid; Prednisolone
Intervention description: 40 mg Adalimumab every other week is administered subcutaneously to all the patients.; 15 mg Methotrexate is weekly administered to all the patients.; At least 1 mg Folic acid is daily administered to all the patients.; 7.5 mg Prednisolone is daily administered to all the patients.
Intervention MeSH terms: Folic Acid; Prednisolone; Adalimumab; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 136.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare the efficacy and safety of adalimumab produced by
      CinnaGen company and AbbVie adalimumab in subjects with active Rheumatoid Arthritis. Patients
      with the diagnosis of active Rheumatoid arthritis according to EULAR criteria (European
      League Against Rheumatism) aged between 18 to 75 years will be included. This study is a
      Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel
      active-controlled non-inferiority clinical trial. The eligible patients are randomized in a
      1:1 ratio to receive CinnoRA® or Humira®. Every two weeks, 40 mg of either of the drugs will
      be administered to each patient subcutaneously along with methotrexate (15 mg/week), folic
      acid (1 mg/day), and prednisolone (7.5 mg/day) over six months.

      The primary objective of the study is to compare the efficacy of test- adalimumab (CinnoRA®)
      and the reference adalimumab (Humira®) in patients with moderately to severely active
      rheumatoid arthritis regarding the evaluation of EULAR criteria based on Disease activity
      score (DAS).

      The secondary objectives of this study are:

        -  To further compare the efficacy of test- adalimumab to reference adalimumab

        -  To assess the safety of test- adalimumab compared to reference adalimumab
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female aged 18-75 years at the time of signing the informed consent form.

          -  Have been diagnosed as having active rheumatoid arthritis (RA) according to The
             European League Against Rheumatism criteria

          -  moderately to severely active RA for at least six months

          -  Patients who have an inadequate response to the treatment with the usual
             non-biological regimen for at least 12 weeks according to their investigator judgment.

          -  Ability to comprehend and willingness to sign the Informed Consent Form for this
             study.

        Exclusion Criteria:

          -  Tuberculosis patient or latent tuberculosis patient (PPD >5mm or abnormal Chest X-ray)

          -  Have been treated previously with any biological agents including any tumor necrosis
             factor inhibitors (including ORENCIA® (abatacept), KINERET® (anakinra), REMICADE®
             (infliximab), ENBREL® (etanercept), CIMZIA® (certolizumab pegol), SIMPONI®
             (golimumab), or Adalimumab).

          -  Have a known hypersensitivity to human immunoglobulin proteins or other components of
             Humira or test- Adalimumab

          -  Women who are pregnant, breastfeeding or planning to become pregnant during the study

          -  Have a positive serological test for hepatitis B or hepatitis C or have a known
             history of infection with human immunodeficiency virus (HIV) of the past three months.

          -  Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound)

          -  Have had a serious infection or have been treated with intravenous antibiotics for an
             infection within eight weeks or oral antibiotics within two weeks prior to screening

          -  Have a history of chronic or recurrent infection

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > two times upper
             limit of normal.

          -  Hemoglobin <8.5 g/dL.

          -  Platelets <125,000/µL.

          -  Leukocyte count <3500/µL.

          -  Serum Creatinine>2 mg/dl

          -  Concomitant use of Prednisolone > 10 mg/day and NSAIDs

          -  Treatment with intravenous, intramuscular, intra-articular and oral corticosteroids
             within four weeks prior to Day 1 (prednisolone, more than 7.5 mg/daily)

          -  Ever used RITUXAN® (rituximab), IMURAN® (azathioprine), or PURINETHOL®
             (mercaptopurine, 6-MP).

          -  Have any of the following conditions:

               1. History of congestive heart failure.

               2. History of acute myocardial infarction or unstable angina within the previous 12
                  months prior to Screening.

               3. History of demyelinating disorders (e.g., MS)

               4. History of multiple sclerosis

               5. History of any malignancy within the previous five years prior to Screening.

               6. Any other disease or disorder which, in the opinion of the Investigator, will put
                  the subject at risk if they are enrolled.