E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sjogren’s Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Primary Sjogren's syndrome is an autoimmune disease. The most common symptoms are mild-to-severe dryness of the eyes and mouth with no other condition that might be contributing to these symptoms. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042846 |
E.1.2 | Term | Syndrome Sjogren's |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 through 75 years at the time of signing the informed consent form (ICF).
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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.
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E.4 | Principal exclusion criteria |
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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).
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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.
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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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 99; safety each visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |