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

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ClinicalTrials.gov Identifier: NCT02334306
Recruitment Status : Completed
First Posted : January 8, 2015
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
MedImmune LLC

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

Condition or disease Intervention/treatment Phase
Primary Sjögren's Syndrome Biological: AMG 557/MEDI5872 Other: Placebo Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomized, Placebo Controlled, Proof of Mechanism Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sjögren's Syndrome
Actual Study Start Date : June 8, 2015
Actual Primary Completion Date : January 16, 2018
Actual Study Completion Date : August 13, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AMG 557/MEDI5872
Fixed subcutaneous (SC) dose of AMG 557/MEDI5872 every week for 3 weeks (Days 1 to 15) and then every 2 weeks for 9 weeks (Days 29 to 85). Beginning on Day 99, all subjects (n = 42) will receive a fixed SC dose of AMG 557/MEDI5872 every week (Days 99 to 113) and every 2 weeks (Days 127 to 183) for an additional 12 weeks.
Biological: AMG 557/MEDI5872
Fixed subcutaneous (SC) dose of AMG 557/MEDI5872 every week for 3 weeks (Days 1 to 15) and then every 2 weeks for 9 weeks (Days 29 to 85). Beginning on Day 99, all subjects (n = 42) will receive a fixed SC dose of AMG 557/MEDI5872 every week (Days 99 to 113) and every 2 weeks (Days 127 to 183) for an additional 12 weeks.

Placebo Comparator: Placebo
Fixed 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). Beginning on Day 99, all subjects (n = 42) will receive a fixed SC dose of AMG 557/MEDI5872 every week (Days 99 to 113) and every 2 weeks (Days 127 to 183) for an additional 12 weeks.
Other: Placebo
Fixed 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). Beginning on Day 99, all subjects (n = 42) will receive a fixed SC dose of AMG 557/MEDI5872 every week (Days 99 to 113) and every 2 weeks (Days 127 to 183) for an additional 12 weeks.




Primary Outcome Measures :
  1. Change in the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) score from Day 1 to Day 99 [ Time Frame: Day 1 to Day 99 ]

Secondary Outcome Measures :
  1. Outcomes in peripheral blood - Change in plasma cell (PC) levels (including plasma blast [PB] levels) from baseline to Day 99 [ Time Frame: Day 1 to Day 99 ]
  2. Outcomes in minor salivary gland tissue - Change in PC levels from baseline to Day 99 [ Time Frame: Day 1 to Day 99 ]
  3. Change in focus score from Day 1 to Day 99 [ Time Frame: Day 1 to Day 99 ]
    Focus score is an assessment of salivary gland inflammation that measures the number of lymphocytes in a 4 mm2 area

  4. Safety and tolerability of multiple subcutaneous (SC) doses of AMG 557/MEDI5872 as measured by safety laboratory tests (hematology, chemistry and urinalysis) [ Time Frame: Day 1 to Day 281 ]
  5. Change in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) score from Day 1 to Day 99 [ Time Frame: Day 1 to Day 99 ]
  6. Outcomes in peripheral blood - Change in follicular helper T cells (TFH) levels from Day 1 to Day 99 [ Time Frame: Day 1 to Day 99 ]
  7. Outcomes in minor salivary gland tissue - Change in TFH levels from Day 1 to Day 99 [ Time Frame: Day 1 to Day 99 ]
  8. Safety and tolerability of multiple subcutaneous (SC) doses of AMG 557/MEDI5872 as measured by the number of subjects with adverse events, including serious adverse events, treatment-related adverse events and adverse events of special interest [ Time Frame: Day 1 to Day 281 ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02334306


Locations
United States, California
Research Site
San Francisco, California, United States, 94143
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20892-1190
United States, Pennsylvania
Research Site
Pittsburgh, Pennsylvania, United States, 15213
France
Research Site
Brest Cedex, France, 29609
Research Site
Le Kremlin-bicêtre, France, 94275
Research Site
Lille Cedex, France, 59037
Research Site
Paris Cedex 13, France, 75651
Research Site
Paris, France, 75014
Research Site
Strasbourg, France, 67098
Sweden
Research Site
Stockholm, Sweden
United Kingdom
Research Site
London, United Kingdom, EC1M 6BQ
Research Site
Newcastle-upon-Tyne, United Kingdom, NE2 4HH
Research Site
Swindon, United Kingdom, SN3 6BB
Sponsors and Collaborators
MedImmune LLC
Amgen
Investigators
Principal Investigator: Maria Dall'Era, MD University of California, San Francisco
Principal Investigator: Ghaith Noaiseh, MD University of Pittsburgh

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02334306     History of Changes
Other Study ID Numbers: D5181C00001
First Posted: January 8, 2015    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Sjogren's Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases