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

NCT02579239 | Completed Phase 1 Results

• 2 other identifiers: ATYR1940-C-0042015-001910-88
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 6

Brief Summary

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

Conditions

Limb-Girdle Muscular Dystrophies; Facioscapulohumeral Muscular Dystrophy

Keywords

LGMD2B; FSHD

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14

  Baseline, Week 14

Study Arms (2)

Group A - FSHD

EXPERIMENTAL

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; Biological: Placebo

Group B - LGMD2B and FSHD

EXPERIMENTAL

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; Biological: Placebo

Interventions

ATYR1940 BIOLOGICAL

Concentrate for solution for infusion

Group A - FSHD; Group B - LGMD2B and FSHD

Placebo BIOLOGICAL

Concentrate for solution for infusion

Group A - FSHD; Group B - LGMD2B and FSHD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• aTyr Pharma, Inc.: lead

Study Sites (6)

University of California, Irvine, ALS and Neuromuscular Center

Irvine, California, 92697, United States

Location

Kennedy Krieger Institute; The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Rigshospitalet, University of Copenhagen

Copenhagen, Denmark

Location

Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)

Marseille, 13385, France

Location

Institut de Myologie, Hôpital Pitié-Salpêtrière

Paris, France

Location

MeSH Terms

Conditions

Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Facioscapulohumeral; Limb-girdle muscular dystrophy, type 2B

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: aTyr Pharma

clinicaltrials@atyrpharma.com

858 731 8389

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: October 19, 2015
• Study Start: November 30, 2015
• Primary Completion: October 5, 2016
• Study Completion: October 5, 2016
• Last Updated: October 19, 2023
• Results First Posted: October 19, 2023

Record last verified: 2023-09

Locations

US (3); FR (2); DK (1)