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

NCT02603562 | Completed Phase 1 Results DMC

• 2 other identifiers: ATYR1940-C-0032014-003346-27
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 7

Brief Summary

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

Conditions

Facioscapulohumeral Muscular Dystrophy (FSHD)

Keywords

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. 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 Outcomes (4)

• Number of Participants With Positive Anti-Drug Antibodies (ADA)

  Baseline up to Week 12

• Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL)

  Baseline up to Week 12

• Number of Participants With Infusion-Related Reactions

  Baseline up to Week 12

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

  Baseline, Week 14

Study Arms (1)

ATYR1940

EXPERIMENTAL

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

Interventions

ATYR1940 BIOLOGICAL

Concentrate for solution for infusion

ATYR1940

Eligibility Criteria

• Age: 16 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• aTyr Pharma, Inc.: lead

Study Sites (7)

Stanford University

Stanford, California, 94305, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

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

Marseille, 13385, France

Location

Institut de Myologie

Paris, 75651, France

Location

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral

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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 13, 2015
• Study Start: March 30, 2016
• Primary Completion: December 12, 2016
• Study Completion: December 12, 2016
• Last Updated: October 19, 2023
• Results First Posted: October 19, 2023

Record last verified: 2023-09

Locations

IT (1); US (4); FR (2)