E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Facioscapulohumeral muscular dystrophy |
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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] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064087 |
E.1.2 | Term | Facioscapulohumeral muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of multiple doses of intravenous (IV) ATYR1940 in adults 18 to 65 years of age, inclusive, with FSHD |
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E.2.2 | Secondary objectives of the trial |
Explore pharmacodynamic (PD) changes in the following biological parameters:
• FSHD-related inflammatory immune responses in skeletal muscle, as assessed by quantitative magnetic resonance imaging (MRI).
• FSHD-related inflammatory immune state in peripheral blood, as assessed by:
• Circulating immune proteins such as cytokines.
• Ex vivo inflammatory immune protein (including cytokines) release from peripheral blood mononuclear cells (PBMCs).
• Immunophenotyping (general and FSHD-related) of circulating PBMCs.
Explore PD changes in the following clinical parameters:
• Manual muscle testing (MMT), as determined by the Investigator.
• Individualized Neuromuscular Quality of Life (INQoL) instrument, as determined by the patient. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a male or female aged 18 to 65 years, inclusive.
2. Patient has an established, genetically-confirmed, diagnosis of FSHD with clinical findings meeting existing criteria.
3. Patient has provided written informed consent after the nature of the study has been explained and prior to the performance of any research-related procedures.
4. Patient is, in the Investigator’s opinion, willing and able to comply with all study procedures.
5. Cohorts ≥2 only: Patient has imaging findings meeting defined criteria for muscle inflammation in at least 1 skeletal muscle (MRI criteria). |
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E.4 | Principal exclusion criteria |
1. Patient is currently receiving treatment with an immunomodulatory agent or has a history of such treatment, including targeted biological therapies (e.g., etanercept, omalizumab) within the 3 months before Baseline; corticosteroids within 4 weeks before Baseline; or non-steroidal anti-inflammatory agents (NSAIDs) within 2 weeks before Baseline.
2. Patient has evidence of an alternative diagnosis other than FSHD, based on prior muscle biopsy or genetic test findings.
3. Patient has a presumptive diagnosis of FSHD, based on clinical assessment, but does not yet have genetic confirmation of the diagnosis.
4. Patient has a severe retinopathy.
5. Patient has a history of obstructive or restrictive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for interstitial lung disease on Screening chest radiograph.
6. Patient has a history of anti-synthetase syndrome, prior Jo-1 antibody (Ab)-positivity, or has a positive or equivocally positive test result during Screening.
7. Patient has symptomatic cardiomyopathy or severe cardiac arrhythmia that may, in the Investigator's opinion, limit the patient's ability to complete the study protocol.
8. Patient has abnormal baseline findings, medical condition(s), or laboratory findings that, in the Investigator's opinion, might jeopardize patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
9. Patient has evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention or other treatment or may not allow safe participation.
10. Patient has used any investigational product or device (other than a mobility assistance device) within 30 days before Baseline.
11. If female and of childbearing potential (premenopausal and not surgically sterile), patient has a positive pregnancy test at Screening or is unwilling to use contraception from the time of Screening through the 1-month Follow-up visit. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device.
12. If male, patient is unwilling to use a condom plus spermicide during sexual intercourse from the time of Screening through the 1 month Follow-up visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and Tolerability endpoints:
• Change from Baseline of physical examination.
• Incidence of AEs.
• Change from Baseline in safety laboratory test results.
• Change from Baseline in ECG findings.
• Change from Baseline in vital sign measurements and pulmonary evaluations.
• Antibody test results.
• Incidence of infusion reactions and infusion site examination findings.
PK Endpoints:
• Standard PK parameters (Cmax, tmax, t1/2, etc). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs: visites 1 to 9
Cinical laboratory test results & vital signs: Screening, visits 1 to 9
ECG: Screening, visits 2, 4, 6, 8 and 9
Pulmonary function tests: Screening, visits 3, 5, 8 and 9
Peripheral venous O2 saturation: visits 1, 2, 3, 4 and 6
ADA titers: Screening, visits 3 to 9
Jo-1 antibody tests: Screening, visits 3 to 9
PK blood sampling: Cohort 1 = visits 2 to 7, Cohort ≥2 = visits 2 to 7 |
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E.5.2 | Secondary end point(s) |
PD Endpoints:
• Changes in FSHD-related inflammatory immune state in peripheral blood and muscle.
• Changes in the clinical parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
MRI & INQoL: Screening and visit 7
MMT: Sceening and visits 3, 5 and 7
Serum/plasma for biomarkers: Screening, visits 1, 2, 5 and 7
Immunophenotyping in PBMCs & Ex vivo immune protein release: visits 1, 5 and 7
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
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 |
Tolerability, Immunogenecity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b/2a: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics |
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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 | No |
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
| 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 | 3 |
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 |
Italy |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Last visit of the last patient, including the 1 to 3-month follow-up visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |