E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Seropositive primary Sjögren’s syndrome |
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E.1.1.1 | Medical condition in easily understood language |
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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 | PT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
• To compare the effect of a single i.v. dose VAY736 versus placebo on the clinical disease activity of primary Sjögren’s syndrome patients as measured by the change of a modified EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) between base line and week 12
• To assess the safety and tolerability of a single i.v. dose VAY736 in patients with primary Sjögren’s syndrome as measured by adverse events (AEs)
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of a single i.v. dose VAY736 versus placebo on self-reported outcomes in pSS patients at 12 weeks compared to baseline as measured by the EULAR Sjögren’s Syndrome Patient Reported Intensity (ESSPRI), the Short Form (36) Health Survey (SF-36), and the Multidimensional Fatigue Inventory (MFI) Questionnaire.
• To determine the changes in the physician global assessment of the patient’s overall disease activity between baseline and week 12 as recorded by a visual analog scale (VAS)
• To determine the changes in the patients’ global assessment of their disease activity between baseline and week 12 as recorded by a VAS
• To determine the pharmacokinetics following a single dose i.v. VAY736 in pSS patients
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed
2. Male and female subjects age 18 to 75 years of age included
3. Fulfilled revised European US consensus criteria for pSS (Vitali et al 2002); if key inclusion criteria are missing from medical history, information will be obtained at screening and may be used as a baseline value if required
4. ESSDAI value ≥ 6
5. Elevated serum titers at screening of ANA (≥ 1:160) and of RF
OR
Seropositive at screening for anti-SSA (± anti-SSB) antibodies
6. Stimulated whole salivary flow rate at screening of > 0 mL/min
7. Subjects must weigh at least 50 kg and no more than 150 kg to
participate in the study, and must have a body mass index (BMI) within
the range of 18 - 35 kg/m2
8. Able to communicate well with the investigator, to understand and
comply with the requirements of the study. |
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E.4 | Principal exclusion criteria |
- Prior or previous use of (specific dosages and intervals prior to study start may apply): B-cell depleting therapy (e.g., rituximab), Prednisone, anti-BAFF mAb, CTLA4-Fc Ig (abatacept), anti-TNF-α mAb, cyclophosphamide, methotrexate, azathioprine and medications known to cause dry mouth. Hydroxychloroquine or methotrexate in a consistent dose for ≥ 3 months prior to randomization is allowed.
- Active or recent history of clinically significant infection
- Vaccination within 2 month prior to study
- History of primary or secondary immunodeficiency
- Other protocol-defined inclusion/exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary aim of this study is to evaluate the effect of a single i.v. dose VAY736 on the clinical disease activity of primary Sjögren’s syndrome patients as measured by the ESSDAI at week 12 compared to baseline. The statistical analysis model will include data on the ESSDAI from all timepoints at which it was recorded (baseline, weeks 6, 12 and 24) but the primary comparison is made for week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy variable is the ESSDAI recorded at baseline and week 12. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy variables supporting the exploratory objectives are:
• EULAR Sjögren’s Syndrome Patient Reported Intensity (ESSPRI) change from baseline.
• Change in physician global assessment of the patient’s overall disease activity between baseline and week 12 as recorded by a visual analog scale (VAS)
• Change in the patient’s global assessment of their disease activity between baseline and week 12 as recorded by a VAS
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary efficacy variables will be analyzed following the same approach used for the primary efficacy variable.
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability, immunogenicity |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The study will complete when the last subject completes their Study Completion visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator.
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |