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

NCT02334306 | Completed Phase 2 Results FDA Drug

• 1 other identifier: D5181C00001
• Study Type: interventional
• Target: 32
• Locations: 4 countries
• Sites: 13

Brief Summary

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

Conditions

Primary Sjögren's Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Day 1 predose) and Day 99

Secondary Outcomes (7)

• 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

Study Arms (2)

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.

Biological: AMG 557/MEDI5872

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.

Other: Placebo

Interventions

AMG 557/MEDI5872 BIOLOGICAL

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).

MEDI5872 210 mg

Placebo OTHER

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.

Placebo/MEDI5872 210 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• MedImmune LLC: lead
• Amgen: collaborator

Study Sites (13)

Research Site

San Francisco, California, 94143, United States

Location

Research Site

Bethesda, Maryland, 20892-1190, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Research Site

Brest, 29609, France

Location

Research Site

Le Kremlin-Bicêtre, 94275, France

Location

Research Site

Lille, 59037, France

Location

Research Site

Paris, 75651, France

Location

Research Site

Paris, 75679, France

Location

Research Site

Strasbourg, 67098, France

Location

Research Site

Stockholm, Sweden

Location

Research Site

London, EC1M 6BQ, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

Research Site

Swindon, SN3 6BB, United Kingdom

Location

Related Links

• Related Info
• Related Info
• Related Info

Results Point of Contact

• Title: Gabor Illei
• Organization: MedImmune, LLC

information.center@astrazenea.com

+1 240 558 0038 118

Study Officials

• Maria Dall'Era, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ghaith Noaiseh, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2014
• First Posted: January 8, 2015
• Study Start: June 8, 2015
• Primary Completion: January 16, 2018
• Study Completion: August 13, 2018
• Last Updated: March 19, 2019
• Results First Posted: March 19, 2019

Record last verified: 2019-02

Locations

US (3); SE (1); GB (3); FR (6)