MedImmune Sjogren's Syndrome Study

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-003896-41-GB
• Date of registration: 05/02/2015
• Prospective Registration: Yes
• Primary sponsor: MedImmune, LLC
• Public title: MedImmune Sjogren's Syndrome Study
• Scientific 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 Sjogren’s Syndrome
• Date of first enrolment: 27/03/2015
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003896-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trial Enquiries
• Affiliation: MedImmune, LLC

• Name: Clinical Trial Enquiries
• Affiliation: MedImmune, LLC

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 18 through 75 years at the time of signing the informed consent form (ICF).
……
6. Fulfill American-European Consensus Group (AECG) criteria for pSS.
7. European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score = 6.
8. Positive anti-SS-A and/or anti-SS-B autoantibodies AND at least one of the following laboratory abnormalities:
a. Immunoglobulin G (IgG) > 13 g/L
b. Rheumatoid factor (RF) level > upper limit of normal (ULN)
c. Positive test for cryoglobulins
9. Willingness to undergo protocol-required minor salivary gland biopsies.
10. Meet all of the following tuberculosis (TB) criteria (see protocol)
11. Immunization up to date as determined by local standard of care.

For a detailed list of inclusion criteria, please refer to the protocol.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
..
3. Previous treatment with AMG 557/MEDI5872.
4. Evidence of signs or symptoms of a viral, bacterial, or systemic fungal infection within 2 weeks (14 days) prior to randomization (Day 1) according to the assessment of the investigator; any infection requiring intravenous (IV) antibiotic or antiviral treatment within 8 weeks of randomization (Day 1); history of herpes zoster within 3 months prior to randomization (Day 1).
...
6. Evidence of significant renal insufficiency, defined by estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73m2.
7. Positive test at screening for either hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
...
16. 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).
...
20. Receiving any of the following:
a. Corticosteroids:
i. > 10 mg/day oral prednisone (or equivalent);
ii. Any change or initiation of new dose of oral corticosteroids within 4 weeks prior to signing the ICF through randomization (Day 1);
iii. Intramuscular, IV, or intra-articular corticosteroids within 4 weeks prior to signing the ICF through randomization (Day 1);
iv. 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:
i. > 20 mg/week methotrexate;
ii. Any change or initiation of new dose of methotrexate within 4 weeks prior to signing the ICF through randomization (Day 1);
iii. 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. Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine eye drops (Restasis) within 2 weeks prior to signing the ICF through randomization (Day 1).

For a detailed list of exclusion criteria, please refer to the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary Sjogren’s Syndrome
MedDRA version: 18.1 Level: LLT Classification code 10042846 Term: Syndrome Sjogren's System Organ Class: 100000004859

Intervention(s)

Product Name: AMG 557/MEDI5872
Product Code: AMG 557/MEDI5872
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMG 557/MEDI5872
Current Sponsor code: AMG 557/MEDI5872
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective is to evaluate the effect of AMG 557/MEDI5872 compared to placebo in reducing objective measures of overall disease activity in subjects with primary Sjogren’s syndrome (pSS).

Secondary Objective: The secondary objectives are:
• To evaluate the effect of AMG 557/MEDI5872 compared to placebo on peripheral blood and salivary gland biomarkers in subjects with pSS.
• To evaluate the safety and tolerability of multiple subcutaneous (SC) doses of AMG 557/MEDI5872 in subjects with pSS.
• To evaluate the effect of AMG 557/MEDI5872 compared to placebo in reducing subjective measures of overall disease activity.

Timepoint(s) of evaluation of this end point: Day 99

Primary end point(s): The primary endpoint of the study is the change in the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score from Baseline to Day 99.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints of the study are:
• Biomarkers:
Outcomes in peripheral blood
? Change in plasma cell (PC) levels (including plasma blast [PB] levels) from Baseline to Day 99
? Change in T follicular helper (TFH) levels from Baseline to Day 99
Outcomes in minor salivary gland tissue
? Change in PC levels from Baseline to Day 99
? Change in TFH levels from Baseline to Day 99
Focus score
? Change in focus score from Baseline to Day 99
• Safety and tolerability of multiple SC doses of AMG 557/MEDI5872 as measured by the incidence of treatment-emergent adverse events, treatment-emergent serious adverse events, adverse events of special interest, and laboratory abnormalities
• Change in European League Against Rheumatism Sjogren’s Syndrome Patient Reported Index score from Baseline to Day 99
Exploratory endpoints of the study are provided in the protocol

Timepoint(s) of evaluation of this end point: Day 99; safety each visit

Secondary ID(s)

D5181C00001

NCT02334306

Source(s) of Monetary Support

MedImmune, LLC

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 23/08/2019
• Date Completed: 13/08/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003896-41/results