Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA)
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Otilimab (GSK3196165); csDMARD(s)
Intervention description: GSK3196165 solution in vial/pre-filled syringe (PFS) and auto injector (AI) to be administered SC.; Stable dose of csDMARD(s) as standard of care (SoC).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants who received GSK3196165 in their qualifying study will continue in this study on the same dose. Participants who received a comparator (tofacitinib or sarilumab) in their qualifying study will be centrally randomized using interactive response technology (IRT) in a ratio of 1:1 to either GSK3196165 90 mg or 150 mg.
Masking: Double (Participant, Investigator)
Masking description: This is a parallel group treatment study with two arms that are initially participant and investigator blinded. A participant's treatment allocation will remain blinded at least until their qualifying study has been reported.
Enrollment: 2916.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid arthritis; GSK3196165; Otilimab; Long-term safety; Long-term efficacy

Summary:

      RA is a chronic, systemic inflammatory autoimmune disease which requires treatment for a long
      time period, hence it is important to study the long-term safety and efficacy of the
      continuous treatment with GSK3196165 over several years. This is a Phase 3, multicenter,
      parallel group treatment and long-term extension study primarily to assess safety with
      efficacy assessment as a secondary objective. Adult participants with RA who have completed
      the treatment phase of a qualifying GSK3196165 clinical studies (Phase 3 studies contRAst 1
      (201790: NCT03980483), contRAst 2 (201791: NCT03970837) and contRAst 3 (202018: NCT04134728)
      and who, in investigator's judgement will benefit from extended treatment with GSK3196165
      will be included in this study (contRAst X [209564: NCT04333147]). Participants will continue
      to receive the same background conventional synthetic disease modifying anti-rheumatic
      drug(s) [csDMARD(s)] treatment as they received in their qualifying study. Eligible
      participants will be enrolled to receive weekly GSK3196165 90 milligrams (mg) or 150 mg by
      subcutaneous (SC) injection. The anticipated study duration is approximately 4 years which
      will enable participants to receive treatment with GSK3196165 until it is expected to become
      commercially available. Approximately 3000 participants from the qualifying studies will
      participate in this long-term extension study
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with rheumatoid arthritis who are aged >=18 years at the time of signing
             informed consent, who have completed one of the qualifying GSK3196165 clinical studies
             and who, in the opinion of the investigator, may benefit from treatment with
             GSK3196165.

          -  Body weight >=40 kilograms (kg).

          -  Male or female participants are eligible to participate as long as they meet the
             contraceptive eligibility criteria and agree to abide by the contraceptive
             requirements.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol.

          -  For participants on methotrexate (MTX): must be willing to continue treatment with
             oral folic acid (at least 5 mg/week) or equivalent while receiving MTX (mandatory
             co-medication for MTX treatment).

        Exclusion Criteria:

          -  Had study intervention permanently discontinued at any time during a qualifying study
             except any participant with a new diagnosis of latent Mycobacterium tuberculosis (TB)
             at the end of study assessment in a qualifying study and currently undertaking or
             willing to complete at least 4 weeks of anti-TB treatment off study treatment, per
             world health organization (WHO) or national guidelines prior to re-commencing therapy
             and complete the remainder of anti-TB treatment while on study.

          -  Evidence of latent TB (as documented by a positive QuantiFERON-TB Gold plus test or
             T-SPOT.TB test, no findings on medical history or clinical examination consistent with
             active TB, and a normal chest radiograph) except for participants that

               -  Are currently undertaking or willing to complete at least 4 weeks of anti-TB
                  therapy off study treatment, as per WHO or national guidelines prior to re-
                  commencing study treatment and agree to complete the remainder of anti-TB
                  treatment while in the study or

               -  Had documented evidence of satisfactory anti-TB treatment as per WHO or national
                  guidelines following review by a physician specializing in TB on entry to a
                  qualifying study.

          -  Current or previous active TB regardless of treatment.

          -  Were temporarily discontinued from study intervention at the time of the final study
             visit of a qualifying study and, in the opinion of the investigator, participation in
             the extension study poses an unacceptable risk for the participant's participation.

          -  A new cancer or malignancy except for basal and squamous cell carcinoma of the skin or
             in situ carcinoma of the cervix treated and considered cured by the investigator.

          -  Have developed any lymphoproliferative disorder during a qualifying study, such as
             Epstein Barr Virus (EBV) related lymphoproliferative disorder, or signs and symptoms
             suggestive of current lymphatic disease.

          -  Have significant uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic,
             renal, gastrointestinal, endocrine, hematologic, or neuropsychiatric disorders, or
             abnormal laboratory values that developed during a qualifying study that, in the
             opinion of the investigator, poses an unacceptable risk for the participant's
             participation.

          -  Participants who are expected to be non-compliant with restrictions on medications and
             vaccinations prior to the study, during the study or during the 8-week safety
             follow-up of the study.

          -  Participants who are currently participating in any interventional clinical study
             other than a qualifying GSK3196165 clinical study.

          -  Abnormal chest radiograph within the last 12 weeks judged by the investigator as
             clinically-significant.

          -  Pregnant or lactating, or women planning to become pregnant or initiating
             breastfeeding.

          -  History of sensitivity to any of the study treatments, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or Medical
             Monitor, contraindicates their participation.