E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sjögren’s syndrome Mixed connective tissue disease |
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E.1.1.1 | Medical condition in easily understood language |
Sjögren’s syndrome Mixed connective tissue disease |
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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 | 21.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027754 |
E.1.2 | Term | Mixed connective tissue disease |
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 |
- SjS participants: to evaluate the efficacy of MHV370 compared to placebo based on change from baseline in ESSDAI at Week 24 - MCTD participants: to evaluate the efficacy of MHV370 compared to placebo based on change from baseline in Physician Global Assessment (PhGA) at Week 24 |
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E.2.2 | Secondary objectives of the trial |
SjS and MCTD: To evaluate the efficacy of MHV370 compared to placebo based on change from baseline on patient and physician-reported outcomes over time up to Week 24 To evaluate the safety and tolerability of MHV370 To assess PK parameters of MHV370 SjS: To explore the effect of MHV370 on quantitative salivary flow (unstimulated) over 24 weeks To explore the effect of MHV370 on quantitative tear production over 24 weeks MCTD: To evaluate the efficacy of MHV370 based on change from baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1, FEV2, FEV3) over time up to Week 24 To evaluate the efficacy of MHV370 based on change from baseline in the diffusing capacity of lungs for carbon monoxide (DLCO) over time up to Week 24 To evaluate the efficacy of MHV370 based on change from baseline in the patient reported outcome on lung function To evaluate the efficacy of MHV370 based on change from baseline in Raynaud's Condition Score (RCS) over time up to Week 24 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
SjS and MCTD: - Fully vaccinated with any locally approved COVID-19 vaccination at least 4 weeks prior to baseline SjS: - Unstimulated whole salivary flow rate of > 0 mL/min at screening - Classification of Sjögren's Syndrome according to the 2016 ACR/EULAR criteria at screening - Screening ESSDAI (based on weighted score) ≥ 5 from 8 defined domains (biologic, hematologic, articular, cutaneous, glandular, lymphadenopathy, renal, constitutional). MCTD: - Diagnosis of MCTD based on a)Raynaud’s phenomenon b) At least two of the four following signs: i) synovitis, ii) myositis, iii) swollen fingers and vi) interstitial lung disease - Patients with overlap syndromes, i.e. patients meeting diagnostic criteria for systemic autoimmune disease other than MCTD may be included unless they have major organ involvement as judged by the investigator
Other protocol inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
SjS and MCTD: - Prior use of B-cell depleting therapy within 6 months of baseline. For participants who received B-cell depleting therapy within 6 -12 months of baseline visit, B-cell count should be within normal range - Prior treatment with any of the following within 3 months of baseline: CTLA4-Fc Ig (abatacept), Anti-TNF mAb, Intravenous Ig, Plasmapheresis, i.v. or oral cyclophosphamide, i.v. or oral cyclosporine A - Screening CBC laboratory values as follows: Hemoglobin levels < 8 g/dL (< 5 mmol/L), Total leukocyte count < 2,000/μL (2 x 109/L), Platelets < 50,000/μL (50 x 109/L), Neutrophil count < 1,000/μL (1 x 109/L) - Pregnant or nursing (lactating) women - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they use a highly effective method of contraception SjS: - Sjögren’s Syndrome overlap syndromes where another autoimmune disease constitutes the primary illness - Required regular use of medications known to cause, as a major side effect, dry mouth / eyes
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
- SjS participants: change from baseline in Eular Sjögren's Disease Activity Index (ESSDAI) after 24 weeks of treatment - MCTD participants: change from baseline in physician’s global assessment scale (PhGA) after 24 weeks of treatment |
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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) |
SjS and MCTD participants: - Maximum Observed Blood Concentrations (Cmax) of MHV370 at steady state - Area under the blood concentration-time curve from time zero to time of last measurable concentration (AUClast) of MHV370 at steady state - Time to Reach Maximum Blood Concentrations (Tmax) of MHV370 at steady state - Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale - Change from baseline in Physician Global Assessment (PhGA) SjS participants: - Change from baseline in Eular Sjögren’s Syndrome Disease Activity Index (ESSDAI) - Change from baseline in Eular Sjögren's Syndrome Patient Reported Index (ESSPRI) - Change from baseline to the salivary flow rate - Change from baseline to the Schirmer’s test MCTD participant: - Change from baseline in articular and pulmonary domains of the Eular Sjögren’s Syndrome Disease Activity Index (ESSDAI) - Change from baseline in Forced Vital Capacity (FVC) - Change from baseline in Forced expiratory volume during the first second (FEV1) of a forced breath - Change from baseline in Forced expiratory volume during the first two seconds (FEV2) of a forced breath - Change from baseline in Forced expiratory volume during the first three seconds (FEV3) of a forced breath - Change from baseline in the diffusing capacity of the lungs for carbon monoxide (DLCO) - Change from baseline in King’s Brief Interstitial Lung Disease (K-BILD) - Change from baseline in Raynaud’s Condition Score (RCS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As per the assessment schedule provided in scope of Clinical Study Protocol |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 10 |
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 |
China |
Israel |
Taiwan |
Germany |
Hungary |
Poland |
Spain |
Switzerland |
United Kingdom |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |