Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD) (FSHD)

An Open-Label, Intrapatient Dose Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients With Limb Girdle and Facioscapulohumeral Muscular Dystrophies

The purpose of this study is to assess the safety and biological activity of ATYR1940 in participants with LGMD2B and FSHD.

Study Overview

• Status: Completed
• Conditions: Limb-Girdle Muscular Dystrophies; Facioscapulohumeral Muscular Dystrophy
• Intervention / Treatment: Biological: ATYR1940; Biological: Placebo

Detailed Description

ATYR1940-C-004 is a Phase1b/2 open-label intrapatient study dose escalation study aiming to evaluate the safety, tolerability, immunogenicity, biological activity of intravenous ATYR1940, administered once weekly for 8 weeks, then twice a weekly for 4 weeks in adult patients with LGMD2B and FSHD. Approximately 8 LGMD2B and 8 FHSD patients will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet, University of Copenhagen
• France
  • Marseille, France, 13385
    • Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
  • Paris, France
    • Institut de Myologie, Hôpital Pitié-Salpêtrière
• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine, ALS and Neuromuscular Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute; The Johns Hopkins University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • OSU Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provided informed consent.
• Investigator's opinion, participant is willing and able to complete all study procedures and comply with the study visit schedule.

Participant with LGMD2B:

• Established, genetically confirmed diagnosis of LGMD2B.
• Either the presence of a short tau inversion recovery (STIR) positive muscle on lower extremity skeletal muscle magnetic resonance imaging (MRI), or, if no STIR positive muscles, meets muscle biomarker criteria.

Participant with FSHD:

• Established, genetically confirmed diagnosis of FSHD.
• The presence of a STIR positive muscle on lower extremity skeletal muscle MRI.

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 on a chronic basis within 30 days 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 LGMD2B or 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A - FSHD; Participants with FSHD will receive single dose of placebo intravenous (IV) infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 milligrams/kilograms (mg/kg) once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	Biological: ATYR1940; Concentrate for solution for infusion; Biological: Placebo; Concentrate for solution for infusion
Experimental: Group B - LGMD2B and FSHD; Participants with LGMD2B and FSHD will receive single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	Biological: ATYR1940; Concentrate for solution for infusion; Biological: Placebo; Concentrate for solution for infusion

What is the study measuring?

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. An AE was 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. An SAE was 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, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or 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 Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE	ECG parameters that were evaluated included heart rate, PR, and QR and QT intervals. A clinically significant ECG abnormality was based upon the 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 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)
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]); 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 Vital Sign Abnormality Resulting in a TEAE	The vital sign parameters that were evaluated included heart rate, systolic and diastolic blood pressure, and respiration rate as well as temperature. 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
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14	MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.	Baseline, Week 14

Collaborators and Investigators

• Sponsor: aTyr Pharma, Inc.
• Investigators: Study Director: Kelly Blackburn, aTyr Pharma

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2015
• Primary Completion (Actual): October 5, 2016
• Study Completion (Actual): October 5, 2016

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimated): October 19, 2015

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: LGMD2B; FSHD
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Facioscapulohumeral
• Other Study ID Numbers: ATYR1940-C-004; 2015-001910-88 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No