An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Upadacitinib; Pneumococcal 13-valent conjugate vaccine (PCV-13)
Intervention description: Tablet taken orally; Administered by intramuscular injection
Intervention MeSH terms: Upadacitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 493.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Musculoskeletal Disease; Arthritis; Joint Diseases; Anti-inflammatory Agents; Antirheumatic agents

Summary:

      The primary objective of the study is to evaluate the long-term safety, tolerability, and
      efficacy of upadacitinib in adults with rheumatoid arthritis (RA) who have completed a
      preceding randomized controlled trial with upadacitinib.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389)
             with upadacitinib (ABT-494) and did not develop any discontinuation criteria.

          2. If the subject has evidence of new latent tuberculosis (TB) infection, the subject
             must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is
             longer) of an ongoing TB prophylaxis before continuing to receive study drug.

          3. If female, subject must be postmenopausal, OR permanently surgically sterile, OR for
             women of childbearing potential practicing at least one protocol-specified method of
             birth control, that is effective from Study Day 1 through at least 30 days after the
             last dose of study drug.

          4. Subjects must voluntarily sign and date an informed consent, approved by an
             Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
             initiation of any screening or study specific procedures.

        Substudy:

          1. Must currently be enrolled in the main study.

          2. Must have been receiving a stable dose of upadacitinib (either 15 mg QD or 30 mg QD)
             for a minimum of 4 weeks prior to the Vaccination visit.

          3. Must have been on a stable dose of background methotrexate (no change in dose or
             frequency) for a minimum of 4 weeks prior to the Vaccination visit.

          4. If subject is on corticosteroids, must remain on a stable dose of ≤ 10 mg/day of
             prednisone or equivalent corticosteroid therapy for at least 4 weeks after the
             vaccination visit.

          5. Must meet the prescribing specifications as per local label requirements to receive
             Prevnar 13® vaccine.

          6. Willing to receive Prevnar13® vaccine.

        Exclusion Criteria:

          1. Pregnant or breastfeeding female.

          2. Ongoing infections at Week 0 that have not been successfully treated. Subjects with
             ongoing infections undergoing treatment may be enrolled but not dosed until the
             infection has been successfully treated.

          3. Anticipated requirement or receipt of any live vaccine during study participation
             including up to 30 days after the last dose of study drug.

          4. Laboratory values from the visit immediately prior to Baseline Visit (local
             requirements may apply) meeting the following criteria:

               -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × upper
                  limit of normal (ULN)

               -  Estimated glomerular filtration rate by simplified 4-variable Modification of
                  Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m^2

               -  Total white blood cell count (WBC) < 2,000/μL

               -  Absolute neutrophil count (ANC) < 1,000/μL

               -  Platelet count < 50,000/μL

               -  Absolute lymphocytes count < 500/μL

               -  Hemoglobin < 8 g/dL

          5. Enrollment in another interventional clinical study while participating in this study.

          6. Consideration by the investigator, for any reason, that the subject is an unsuitable
             candidate to receive study drug.

        Substudy:

          1. Receiving any conventional synthetic disease modifying antirheumatic drugs (csDMARDs)
             other than methotrexate

          2. Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.

          3. Receipt of any steroid injection within 4 weeks prior to Vaccination visit.

          4. History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar
             13®.

          5. History of any documented pneumococcal infection within the last 6 months prior to the
             vaccination visit.

          6. Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of
             any vaccination for 4 weeks after the vaccination visit.

          7. Receipt of any pneumococcal vaccine.

          8. Subject is not suitable for the sub-study as per the Investigator's judgment.