Clinical trial NCT02334306: A Phase 2a, Randomized, Placebo Controlled, Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sjögren's Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sjögren's Syndrome
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2015-01-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
Secondary outcomes:
measure: Ratio to Baseline in Peripheral Blood Biomarkers at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
measure: Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
measure: Ratio to Baseline in Focus Score at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
measure: Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
measure: Percentage of ESSDAI Responders at Day 99
timeFrame: Baseline (Day 1 predose) and Day 99
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: 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
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: 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
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Research Site
state: California
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Brest Cedex
country: France
facility: Research Site
city: Le Kremlin-bicêtre
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Research Site
city: Swindon
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of California, San Francisco
name: Maria Dall'Era, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Ghaith Noaiseh, MD
role: PRINCIPAL_INVESTIGATOR
References: