MSB11456 in Participants With Moderately to Severely Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: MSB11456; EU-approved RoActemra
Intervention description: Participants will receive MSB11456 subcutaneously, once a week.; Participants will receive EU-approved RoActemra® subcutaneously, once a week.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 604.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MSB11456; RoActemra®

Summary:

      The purpose of the study is to compare the efficacy, safety and immunogenicity of MSB11456
      and EU approved RoActemra® in participants with moderately to severely active rheumatoid
      arthritis.

      Participants will be randomized at the beginning of the Core Treatment Period (Baseline to
      Week 24) to receive either MSB11456 or EU approved RoActemra® once a week (QW). At the
      beginning of the Extended Treatment Period (Week 24 to Week 52), participants who received
      RoActemra® will be re-randomized to either continue receiving RoActemra® QW or switch to
      receive MSB11456 QW.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are ≥18 years of age.

          -  Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/European League
             Against Rheumatism (EULAR) Classification 2010 criteria with disease duration of ≥6
             months.

          -  Have moderately to severely active rheumatoid arthritis.

          -  Must have been treated with methotrexate for at least 12 consecutive weeks immediately
             prior to randomization and are on a stable dose between 10 and 25 mg/week methotrexate
             for the last 8 weeks prior to screening.

          -  Have had previous inadequate clinical response to at least one modifying
             anti-rheumatic drug.

          -  Women of childbearing potential (i.e., considered fertile following menarche and until
             becoming postmenopausal unless permanently sterile) can participate only if they have
             a negative serum pregnancy test at screening and a negative urine pregnancy test at
             Day -1 before randomization. Women of childbearing potential must have used and agree
             to use a highly effective contraception (i.e., methods with a failure rate of less
             than 1% per year), for 4 weeks before randomization and must agree to continue to
             practice adequate contraception for 3 months after the last study drug administration.

          -  Must voluntarily give written informed consent before any study-related activities are
             performed. Participants must read and fully understand the Informed Consent Form and
             the requirements of the study. Participants must be willing to comply with all study
             visits and assessments. Participants must be willing to complete each study procedure.
             Note: A separate Informed Consent Form (containing important information about COVID
             19, clinical research study participation and participant consent) will be provided to
             and signed by each participant to provide information on the general risks of study
             participation related to COVID-19 and to document that it is understood by the
             participant. Another separate Informed Consent Form will be required to be understood
             and signed by partners of male participating patients who become pregnant during the
             study or within 10 weeks after the participating patient's last dose of study drug.

        Exclusion Criteria:

          -  American College of Rheumatology functional class IV as defined by the ACR
             classification of functional status or wheelchair/bedbound.

          -  Previously received tocilizumab, an investigational or licensed biosimilar of
             tocilizumab or any interleukin-6 acting drugs.

          -  Prior use of targeted synthetic disease-modifying anti-rheumatic drugs like janus
             kinase inhibitors.

          -  Prior use of more than 2 biologic treatments for rheumatoid arthritis.

          -  Received a live or attenuated vaccine within 4 weeks prior to randomization.

          -  Participant is considered by the Investigator, for any reason, to be an unsuitable
             candidate for the study. Investigator should specifically evaluate the participant's
             eligibility taking into consideration COVID-19 risk factors and situation.

          -  Has a serious and/or unstable and/or poorly controlled medical condition such as but
             not limited to poorly controlled diabetes, unstable ischemic heart disease,
             uncontrolled hypertension or other cardiovascular, cerebrovascular, cardiovascular,
             gastrointestinal disease, hepatic, renal, hematological, endocrine, nervous system or
             pulmonary disease or other relevant medical condition or a history of clinically
             significant disease or any other condition that, in the opinion of the Investigator,
             would put the participant at risk by participation in the study.

          -  Confirmed or, based on the signs and symptoms observed at the time of assessment,
             suspected active COVID-19 infection at the time of screening and/or randomization.

          -  Has had any infection as follows:

               1. Herpes zoster or any opportunistic invasive infection within 6 months of
                  screening.

               2. Frequent, chronic or recurrent infections.

               3. A positive test for human immunodeficiency virus subtype 1 (HIV-1) or 2 (HIV-2),
                  hepatitis C antibody, hepatitis B surface antigen and/or core antibody for
                  immunoglobulin G and/or immunoglobulin M or total immunoglobulin at screening.

               4. A serious infection within 8 weeks prior to randomization.

               5. Required treatment with oral antibiotics and/or anti-fungal drugs within 14 days
                  prior to randomization.

          -  Medical evidence of active or latent tuberculosis as indicated by a positive
             QuantiFERON®-TB Gold Plus test, chest X-ray and/or clinical examination or has had
             active or latent tuberculosis disease at any time in the past.

          -  Received a COVID 19 vaccine within 4 weeks prior to randomization, are receiving
             ongoing COVID-19 vaccination at the time of screening or plan to receive COVID-19
             vaccination before the completion of the Week 30 visit of the study. COVID-19
             vaccination is considered ongoing if a multidose regimen has been started but has not
             been completed.