Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and biological activity of ATYR1940 in participants with early onset FSHD.

Detailed Description
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A Phase 1b/2 open-label, intraparticipant dose-escalation study aiming to evaluate the safety, tolerability, immunogenicity, biological and pharmacodynamic activity of intravenous ATYR1940, administered once weekly for 12 weeks, in early onset FSHD participants with signs or symptoms prior to 10 years of age.

Official Title
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An Open-Label, Intrapatient Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients With Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy

Conditions
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Facioscapulohumeral Muscular Dystrophy (FSHD)

Intervention / Treatment
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* Biological: ATYR1940


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established, genetically confirmed diagnosis of FSHD. Onset of FSHD signs or symptoms prior to 10 years of age, as documented in the participant's medical record or based on participant or family report. Provide written informed consent or assent In the Investigator's opinion, participant is willing and able to complete all study procedures and comply with the weekly study visit schedule. Exclusion Criteria: Currently receiving treatment with an immunomodulatory agent including targeted biological therapies within the 3 months before baseline; corticosteroids within 3 months before baseline; or high-dose non-steroidal anti-inflammatory agents within 2 weeks before baseline. Currently receiving curcumin or albuterol; use of a product that putatively enhances muscle growth or activity on a chronic basis within 4 weeks before baseline; statin treatment initiation or significant adjustment to statin regimen within 3 months before baseline (stable, chronic statin use is permissible). Use of an investigational product or device within 30 days before baseline. Evidence of an alternative diagnosis other than FSHD or a coexisting myopathy or dystrophy, based on prior muscle biopsy or other available investigations. History of severe restrictive or obstructive lung disease, or evidence for interstitial lung disease on screening chest radiograph. History of anti-synthetase syndrome, prior Jo-1 Ab-positivity, or a positive or equivocally positive Jo-1 Ab test result during screening. Chronic infection, such as hepatitis B, hepatitis C, or human immunodeficiency virus or a history of tuberculosis. Vaccination within 8 weeks before baseline or vaccination is planned during study participation. Symptomatic cardiomyopathy or severe cardiac arrhythmia, that may, in the Investigator's opinion, limit the participant's ability to complete the study protocol. Muscle biopsy within 30 days before baseline.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATYR1940<br>Participants received ATYR1940 intravenous (IV) infusion at doses of 0.3, 1.0, and 3.0 milligrams/kilograms (mg/kg) once weekly using intraparticipant dose escalation for 12 weeks. | Biological: ATYR1940<br>* Concentrate for solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. AEs were defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section. | Up to End of Study (up to Week 25) | 
| Number of Participants With a Clinical Laboratory Abnormality Leading to an AE | Laboratory parameters included hematology (hematocrit, hemoglobin, red blood cell count, white blood cell count with differential [neutrophils, lymphocytes, monocytes, eosinophils, basophils], and platelet count); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total protein, sodium, potassium, bicarbonate, calcium, chloride, magnesium, inorganic phosphate, creatine kinase, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, and cholesterol [nonfasting]); and urinalysis (color, pH, specific gravity, protein, glucose, ketones, and blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Up to End of Study (Up to Week 25) | 
| Number of Participants With an Ocular Abnormality Leading to a TEAE | Ocular parameters included vitreous, retina, macula, choroid, optic nerve, and optic nerve pallor. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Up to End of Study (Up to Week 25) | 
| Number of Participants With an Impact on Hearing From ATYR1940 Treatment |  | Up to End of Study (Up to Week 25) | 
| Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE | Pulmonary evaluations included pulmonary function tests and pulse oximetry. Clinically significant changes were to be reported as adverse events. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Up to End of Study (up to Week 25) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | Titers through Week 12 are summarized. | Baseline up to Week 12 | 
| Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL) | Participants with Jo-1 Ab levels ≥1.5 units/milliliter (U/mL) were to be discontinued from dosing of the study drug. | Baseline up to Week 12 | 
| Number of Participants With Infusion-Related Reactions | Infusion-related reactions included fever, chills, rigors, myalgia, facial erythema, systemic erythema, pallor, facial swelling, chest tightness, difficulty breathing, wheezing, stridor, tachypnea, bronchospasm, cough, tachycardia, significant pulse rate increase from baseline without obvious cause, bradycardia, significant pulse rate decrease from baseline, pre-syncope or syncope, hypotension, orthostatic hypotension, blood pressure swings (including hypertension), skin rash, urticaria, angioedema, pruritus, difficulty speaking, hoarse voice, raspy voice, excessive salivation, difficulty swallowing, nausea, vomiting, cramps, diarrhea; swelling of the throat, tongue, mouth, or lip, and development of a headache especially moderate or greater after start of infusion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Baseline up to Week 12 | 
| Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14 | MMT was graded on a scale from 0 (no movement) to 10 (normal movement). Each side of the body and the position in which each muscle was tested were recorded for each participant. The total MMT score were calculated by averaging a converted-MMT scores across all tested muscle groups. Decreased motor function was indicated by decreased individual muscle or composite MMT score. | Baseline, Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FSHD