A Phase 2a, Randomized, Placebo Controlled, Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sjögren's Syndrome

MedImmune LLC32 enrolled

Overview

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

This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the clinical and biologic efficacy, as well as the safety of SC doses of AMG 557/MEDI5872 in adult subjects with Primary Sjögren's Syndrome.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Primary Sjögren's Syndrome

Interventions

AMG 557/MEDI5872BIOLOGICAL

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).

PlaceboOTHER

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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).

Locations (13)

Research Site

San Francisco, California, United States

Research Site

Bethesda, Maryland, United States

Research Site

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99

The European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (i.e., no, low, moderate, high) according to their severity (no disease activity equals to 0 and for high disease activity the domain score equals 3 or 4). Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. Adjusted mean change and standard error are presented.

Time frame: Baseline (Day 1 predose) and Day 99

Secondary Outcomes

Ratio to Baseline in Peripheral Blood Biomarkers at Day 99

The peripheral blood biomarkers included total plasma cell levels (including plasma blast levels) and T follicular helper (TFH) cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.

Time frame: Baseline (Day 1 predose) and Day 99

Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99

The minor salivary gland biopsy biomarkers included total plasma cell levels, CD4/ inducible T-cell costimulator (ICOS) TFH cells, and PD-1/ICOS TFH cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.

Time frame: Baseline (Day 1 predose) and Day 99

Ratio to Baseline in Focus Score at Day 99

The focus score is a semi-quantitative assessment of focal lymphocytic sialoadenitis, which is defined as the presence of \>= 1 dense aggregate of 50 or more lymphocytes in a 4 mm2 area. Higher numbers are associated with more inflammation.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.