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Clinical Trials/NCT02334306
NCT02334306CompletedPhase 2

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

MedImmune LLC14 sites in 4 countries32 target enrollmentStarted: June 8, 2015Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Phase 2
Status
Completed
Enrollment
32
Locations
14
Primary Endpoint
Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99

Study Overview

Brief Summary

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

Detailed Description

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 Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages
18 Years to 75 Years (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

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 ≥
  • 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/MEDI
  • 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:
  • Belimumab in the past 6 months prior to randomization (Day 1);
  • 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);
  • Abatacept in the past 6 months prior to randomization (Day 1);
  • Tumor necrosis factor inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) in the past 3 months prior to randomization (Day 1);
  • Tocilizumab in the past 3 months prior to randomization (Day 1);
  • 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:
  • 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);
  • 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).
  • 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.
  • 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).
  • 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).

Arms & Interventions

MEDI5872 210 mg

Experimental

Participants will receive a fixed SC dose of 210 mg MEDI5872 every week (QW) from Days 1 to 15 and then every 2 weeks (Q2W) from Days 29 to 85 in double-blind period. In open-label period, participants will continue dosing of MEDI5872 210mg Q2W from Days 99 to 183 and will receive an additional dose of blinded placebo on Day 106.

Intervention: AMG 557/MEDI5872 (Biological)

Placebo/MEDI5872 210 mg

Placebo Comparator

Participants will receive a SC dose of placebo matching with MEDI5872 QW on Days 1, 8, and 15 and then Q2W from Days 29 to 85 in double-blind period. In open-label period, participants will receive a fixed SC dose of 210 mg MEDI5872 QW (Days 99 to 113) and Q2W (Days 127 to 183) in open-label period.

Intervention: Placebo (Other)

Outcomes

Primary Outcomes

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

Time Frame: Baseline (Day 1 predose) and 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.

Secondary Outcomes

  • Ratio to Baseline in Peripheral Blood Biomarkers at Day 99(Baseline (Day 1 predose) and Day 99)
  • Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99(Baseline (Day 1 predose) and Day 99)
  • Ratio to Baseline in Focus Score at Day 99(Baseline (Day 1 predose) and Day 99)
  • Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99(Baseline (Day 1 predose) and Day 99)
  • Percentage of ESSDAI Responders at Day 99(Baseline (Day 1 predose) and Day 99)
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period)
  • Number of Participants With Adverse Events of Special Interest (AESIs)(Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (14)

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