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

Study identifier:D5181C00001

ClinicalTrials.gov identifier:NCT02334306

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Primary Sjögren's Syndrome

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 08 Jun 2015

Primary Completion Date: 16 Jan 2018

Study Completion Date: 13 Aug 2018

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2019 by MedImmune, LLC

Collaborators

Amgen

Inclusion and exclusion 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:
a. Belimumab in the past 6 months prior to randomization (Day 1);
b. 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);
c. Abatacept in the past 6 months prior to randomization (Day 1);
d. Tumor necrosis factor inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) in the past 3 months prior to randomization (Day 1);
e. Tocilizumab in the past 3 months prior to randomization (Day 1);
f. 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:
a. 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);
b.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).
c.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.
d. 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).
e.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).

No locations available

Arms	Assigned Interventions
Experimental: MEDI5872 210 mg 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/Vaccine: AMG 557/MEDI5872 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).
Placebo Comparator: Placebo/MEDI5872 210 mg 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 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.

Arms

Assigned Interventions

Experimental: MEDI5872 210 mg
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/Vaccine: AMG 557/MEDI5872
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).

Placebo Comparator: Placebo/MEDI5872 210 mg
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
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.

Documents available

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Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Maria Dall'Era

UCSF