Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: etanercept pre-filled syringe subcutaneous injection; Oral methotrexate; Placebo for etanercept subcutaneous injection; Placebo for methotrexate; Folic acid (non-investigational product)
Intervention description: etanercept for injection in pre-filled syringes; During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets.
During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.; etanercept placebo for injection in pre-filled syringes; methotrexate placebo capsules; Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.
Intervention MeSH terms: Folic Acid; Etanercept; 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: 371.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy of etanercept monotherapy compared to
      methotrexate monotherapy on maintenance of remission in participants with rheumatoid
      arthritis (RA) who were on etanercept plus methotrexate therapy.

      This is a multicenter, randomized withdrawal, double-blind controlled study in participants
      with rheumatoid arthritis on etanercept plus methotrexate therapy who are in very good
      disease control for 6 months prior to study entry. The study will consist of a 30-day
      screening period, a 24-week open label run-in period, a 48-week double-blind treatment period
      and a 30-day safety follow-up period.
    

Eligibility criteria:

        Inclusion Criteria (Part 1, Run-In Period):

          -  Subjects must be adults with a history of moderate to severe rheumatoid arthritis;

          -  Subjects must be in very good rheumatoid arthritis disease control for ≥ 6 months and
             be in remission as defined by a Simplified Disease Activity Index ≤ 3.3 at screening
             and at the end of the run-in period.

          -  Subjects must be on etanercept 50 mg per week plus methotrexate therapy for ≥ 6 months
             prior to the start of the run-in period. The methotrexate dose must be 10 to 25 mg per
             week for ≥ 6 months prior to the start of the run-in period and the dose must be
             stable for ≥ 8 weeks prior to the start of the run-in period.

          -  Subject has no known history of active tuberculosis, and has a negative test for
             tuberculosis during screening.

        Exclusion Criteria (Part 1, Run-In Period):

          -  Subject has used biologic disease modifying antirheumatic drug other than etanercept
             OR has used an oral janus kinase inhibitor ≤ 6 months prior to run-in visit 1

          -  Subject has any active infection (including chronic or localized infections) for which
             anti-infectives were indicated within 4 weeks prior to run-in visit 1.

          -  Subject has known alcohol addiction or dependency or uses alcohol daily.

          -  Subject has one or more significant concurrent medical conditions per investigator
             judgment, including the following:

               -  poorly controlled diabetes

               -  chronic kidney disease stage IIIb, IV, or V

               -  symptomatic heart failure (New York Heart Association class II, III, or IV)

               -  myocardial infarction or unstable angina pectoris within the past 12 months prior
                  to randomization

               -  uncontrolled hypertension

               -  severe chronic pulmonary disease (eg, requiring oxygen therapy)

               -  multiple sclerosis or any other demyelinating disease

               -  major chronic inflammatory disease or connective tissue disease other than
                  rheumatoid arthritis (eg, systemic lupus erythematosus with the exception of
                  secondary Sjögren's syndrome)

        Inclusion Criteria (Part 2, Treatment Period):

          -  SDAI ≤ 3.3 at run-in visit 3

          -  Subject if female and not at least 2 years postmenopausal or history of hysterectomy,
             bilateral salpingectomy, or bilateral oophorectomy, has a negative urine pregnancy
             test at baseline (day 1).

        Exclusion Criteria (Part 2, Treatment Period):

          -  Any clinically significant change in the Part 1 eligibility criteria during the run-in
             period

          -  SDAI > 3.3 and ≤ 11 on two consecutive visits at least two weeks apart OR SDAI > 3.3
             and ≤ 11 on two or more separate visits OR SDAI > 11 at any time during the run-in
             period

          -  Subject has a clinically significant laboratory abnormality during run-in period which
             in the opinion of the investigator poses a safety risk, will prevent the subject from
             completing the study, or will interfere with the interpretation of the study results
             during the run-in period.

        NOTE: Other inclusion/exclusion criteria may apply per protocol.