A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Experimental: Arm A: DRL_RI; Arm B: Rituxan®/Mabthera®
Intervention description: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion; Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized, double-blind, parallel group, multicenter study to assess the immunogenicity and safety of transitioning subjects with rheumatoid arthritis to biosimilar rituximab (DRL_RI) or continued treatment with Rituxan® or MabThera®
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of the current study is to assess the immunogenicity and safety of
      transitioning subjects with RA to DRL_RI from US-rituximab/EU-rituximab to continued
      treatment with US-rituximab/EU-rituximab.

      The primary objective of this study is to assess the immunogenicity of transitioning subjects
      with RA to DRL_RI (biosimilar rituximab) from US-rituximab/EU-rituximab to continued
      treatment with US-rituximab/EU-rituximab

      To assess the safety of transitioning subjects with RA to DRL_RI from
      US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects aged 18 years or older who have provided valid written
             informed consent.

          2. Subjects with a diagnosis of active RA who are eligible for the subsequent treatment
             course with US-rituximab or EU-rituximab according to the clinical judgment of the
             investigator.

          3. Documented evidence that subject has received at least 1 full course comprising two
             1000 mg infusions of either US-rituximab at least 16 weeks prior to the randomization
             visit or EU-rituximab at least 24 weeks prior to the day of randomization visit.

          4. Subjects receiving a stable dose of weekly methotrexate (MTX) for at least 4 weeks
             prior to randomization (between 7.5 mg and 25 mg) and folic acid (at least 5 mg per
             week.

        EXCLUSION CRITERIA;

          1. Subjects with RA in functional Class IV

          2. Subjects with human immunodeficiency virus (positive HIV1Ab or HIV2Ab), hepatitis B
             virus and/or hepatitis C virus infection, including those with positive results in the
             viral disease screening.

          3. Subjects with active tuberculosis. Subjects with evidence of latent TB or a history of
             TB must have completed treatment or have initiated treatment for at least 1 month
             before the first dose of study treatment (Day 1). TB testing is required only if it is
             required by local regulations or practice.

          4. Active systemic infection.

          5. Severely immunocompromised.

          6. History of severe hypersensitivity to either US-rituximab or EU-rituximab or any of
             its excipients requiring drug discontinuation.

          7. Any serious illness or uncontrolled medical condition, including but not limited to
             severe infections, significant hepatic or renal disease, uncontrolled hypertension
             despite treatment (defined as blood pressure ≥160/95 mmHg), congestive heart failure
             (New York Heart Association [NYHA] Class III or IV), or other severe, uncontrolled
             cardiac disease or uncontrolled diabetes with immediate risk of acute complications.

          8. Any condition that in the opinion of the investigator represents an obstacle for study
             conduct and/or represents a potential unacceptable risk for subjects.

          9. Requires treatment with any biological medicinal product during the study other than
             the study treatment.

         10. Previous treatment with B-cell modulating or cell depleting biologic therapy except
             US-rituximab or EU-rituximab.

         11. Prior participation in this clinical trial or prior participation in any clinical
             trial with any monoclonal antibody within 12 months of screening or prior
             participation in any clinical trial within 3 months of screening or within 5
             half-lives of the investigational drug or until the expected PD effect has returned to
             baseline, whichever is longer.

         12. Treatment with other biologic disease-modifying anti-rheumatic drugs, or Janus kinase
             (JAK) inhibitors administered within 12 weeks before the first dose of rituximab of
             the prior treatment course onwards till the date of randomization.

         13. Subjects with the following laboratory abnormalities:

               -  Subjects with screening total white blood cell count <3000/μL, platelets
                  <100,000/μL, neutrophils <1,500/μL, or hemoglobin <8.5 g/dL

               -  Abnormal liver function tests such as aspartate aminotransferase, alanine
                  aminotransferase, or alkaline phosphatase >2 × upper limit of normal (ULN). A
                  single parameter >2 × ULN can be re-checked as soon as possible, at least prior
                  to randomization, if required as per the investigator's discretion.

               -  Creatinine clearance (Cockcroft & Gault formula) of less than 50 mL/min.

         14. History of vaccination with live vaccines within 4 weeks of the first dose of study
             treatment (Day 1) or known to require live vaccines during the study.

         15. Lactating or pregnant female.

         16. Women of childbearing potential who do not consent to use highly effective methods of
             birth control (e.g., barrier contraceptives, oral contraceptives, intrauterine
             devices, true abstinence if it allowed as per the country specific regulatory
             requirement [periodic abstinence {e.g., calendar ovulation, symptothermal,
             post-ovulation methods} and withdrawal are not acceptable methods of contraception],
             or sterilization) during treatment and for at least 12 months after the last
             administration of study treatment.

         17. For men involved in any sexual intercourse that could lead to pregnancy, subjects must
             agree to use 1 of the highly effective methods of birth control listed in Exclusion
             Criterion #16 during treatment and for at least 12 months after the last
             administration of study treatment.

         18. Subject with serum IgG < lower limit of normal.