A Phase 2a, Randomized, Placebo Controlled, Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sjögren's Syndrome
Condition: Primary Sjögren's Syndrome
MeSH terms: Sjogren's Syndrome; Syndrome
Intervention: AMG 557/MEDI5872; Placebo
Intervention description: Participants will receive a fixed SC dose of 210 mg MEDI5872 (AMG 557/MEDI5872) QW for 3 weeks (Days 1 to 15) and then Q2W for 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, all participants from double-blind period will receive a fixed SC dose of 210 mg MEDI5872 from Day 99 to Day 183 (QW from Days 99 to 113 for participants from Placebo arm and on Days 99 and 113 for participants from MEDI5872 210 mg arm; and Q2W from Days 127 to 183 for participants from both arms).; The SC dose of placebo every week for 3 weeks (Days 1 to 15) and then every 2 weeks for 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, an additional dose of blinded placebo will be administered on Day 106 for participants who will receive MEDI5872 210mg in double-blinded period.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      A Phase 2a study to evaluate the efficacy and safety of AMG 557/MEDI5872 in Primary Sjögren's
      Syndrome
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 through 75 years at the time of signing the ICF.

          -  Fulfill American-European Consensus Group (AECG) criteria for pSS

          -  ESSDAI score ≥ 6.

          -  Positive anti-SS-A and/or anti-SS-B autoantibodies and at least IgG > 13 g/L or RF
             level > upper limit of normal (ULN) or positive test for cryoglobulins

          -  Willingness to undergo protocol-required minor salivary gland biopsies.

          -  Negative TB test during screening

          -  Immunization up to date as determined by local standard of care.

        Exclusion Criteria:

          -  Previous treatment with AMG 557/MEDI5872.

          -  Evidence of signs or symptoms of a viral, bacterial, or fungal infection within 2
             weeks (14 days) prior to randomization (Day 1) according to the assessment of the
             investigator; any infection requiring IV antibiotic or antiviral treatment within 8
             weeks of randomization (Day 1); history of herpes zoster within 3 months prior to
             randomization (Day 1).

          -  Evidence of significant renal insufficiency

          -  Positive test at screening for hepatitis B, hepatitis C, or human immunodeficiency
             virus (HIV) antibody.

          -  Prior administration of any of the following:

               1. Belimumab in the past 6 months prior to randomization (Day 1);

               2. Rituximab in the past 12 months or CD19+ B cells < 5/µL if rituximab treatment
                  was more than 12 months prior to randomization (Day 1);

               3. Abatacept in the past 6 months prior to randomization (Day 1);

               4. Tumor necrosis factor inhibitors (adalimumab, certolizumab, etanercept,
                  golimumab, infliximab) in the past 3 months prior to randomization (Day 1);

               5. Tocilizumab in the past 3 months prior to randomization (Day 1);

               6. Cyclophosphamide (or any other alkylating agent) in the past 6 months prior to
                  randomization (Day 1); cyclosporine (except for eye drops), tacrolimus,
                  sirolimus, mycophenolate mofetil, azathioprine, or leflunomide in the past 3
                  months prior to randomization (Day 1).

          -  Receiving any of the following:

               1. Corticosteroids: > 10 mg/day oral prednisone (or equivalent); Any change or
                  initiation of new dose within 4 weeks prior to signing the ICF through
                  randomization (Day 1); Intramuscular, IV, or intra-articular corticosteroids
                  within 4 weeks prior to signing the ICF through randomization (Day 1); Any change
                  or initiation of new dose of topical corticosteroids within 2 weeks prior to
                  signing the ICF through randomization (Day 1);

               2. Antimalarials: any increase or initiation of new dose of antimalarials (eg,
                  chloroquine, hydroxychloroquine, quinacrine) within 12 weeks prior to signing the
                  ICF through randomization (Day 1).

               3. Methotrexate: > 20 mg/week methotrexate; Any change or initiation of new dose of
                  methotrexate within 4 weeks prior to signing the ICF through randomization (Day
                  1); Any change in route of administration.

               4. Any increase or initiation of new dose of regularly scheduled nonsteroidal anti
                  inflammatory drugs (NSAIDs) within 2 weeks prior to signing the ICF through
                  randomization (Day 1).

               5. Cevimeline or pilocarpine and cyclosporine eye drops (Restasis): any increase or
                  initiation of new doses within 2 weeks prior to signing the ICF through
                  randomization (Day 1).