Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)

NCT02836418 | Completed Phase 1 Results DMC

• 1 other identifier: ATYR1940-C-006
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 5

Brief Summary

ATYR1940-C-006 is a multi-national, multicenter study being conducted at centers in the United States (US) and Europe who participated in Study ATYR1940-C-003 (Stage 1 only) or Study ATYR1940-C-004 (that is, the parent studies).

Conditions

Facioscapulohumeral Muscular Dystrophy; Limb Girdle Muscular Dystrophy

Keywords

FSHD; LGMD

Outcome Measures

Primary Outcomes (8)

• 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 approximately Week 39)

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

  Summarized titers are reported below.

  Up to End of Study (up to approximately Week 39)

• 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 U/mL were to be discontinued from dosing of the study drug.

  Up to End of Study (up to approximately Week 39)

• 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 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, 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 approximately Week 39)

• 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 approximately Week 39)

• Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE

  ECG parameters that were evaluated included heart rate and PR, 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 approximately Week 39)

• 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 approximately Week 39)

• Change From Baseline in Manual Muscle Testing (MMT) Score at Week 12

  MMT (muscle strength) will be graded using a modified Medical Research Council scale. Scores were converted to 13-point scale (range from 0 \[on contraction palpable\] to 12 \[normal strength\]). An overall total score was calculated by summing all scores for a total possible score of 336. Decreased muscle strength was indicated by a decreased score. An overall total score was calculated as long as 24 of the 28 individual scores were non-missing.

  Baseline, Week 12

Secondary Outcomes (1)

• Change From Baseline in Creatinine Kinase at Week 12

  Baseline, Week 12

Study Arms (1)

ATYR1940

EXPERIMENTAL

Participants will receive ATYR1940 up to 3.0 milligrams per kilograms (mg/kg) intravenous (IV) infusion once weekly until approval of ATYR1940, discontinuation of its development, the study was closed by the Sponsor, or a criterion for study drug discontinuation (up to 34 weeks).

Drug: ATYR1940

Interventions

ATYR1940 DRUG

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:

• Enrolled in and completed the treatment period in the parent study.
• Demonstrated, in the Sponsor's and Investigator's opinions, acceptable tolerability of ATYR1940.
• In the Investigator's opinion, participant has shown acceptable compliance with ATYR1940 and the study procedures in the parent study and is willing and able to comply with all procedures in the current study.
• Is, in the opinion of the Investigator and Sponsor, a suitable candidate for continued ATYR1940 treatment.
• Provide written informed consent or assent after the nature of the study has been explained and prior to the performance of any research-related procedures.

You may not qualify if:

• Is expected to require treatment with curcumin or systemic albuterol (intermittent inhaled albuterol is permissible) during study participation; or use of a product that putatively enhances muscle growth (for example, insulin-like growth factor, growth hormone) or activity (for example, Coenzyme Q, Coenzyme A, creatine, L-carnitine) on a chronic basis; or statin treatment initiation or significant adjustment to statin regimen (stable, chronic statin use is permissible).
• Planned to receive any vaccination during study participation.
• Abnormal baseline findings, medical condition(s), or laboratory findings that, in the Investigator's opinion, might jeopardize the participant's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
• Evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention, other treatment, or may not allow safe participation.
• If female and of childbearing potential (premenopausal and not surgically sterile), has a positive pregnancy test at entry or is unwilling to use contraception from the time of entry through the 3-month Follow-up visit. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device.
• If male, is unwilling to use a condom plus spermicide during sexual intercourse from the time of entry through the 1 month Follow-up visit.

Sponsors & Collaborators

• aTyr Pharma, Inc.: lead

Study Sites (5)

University of California, Irvine, ALS and Neuromuscular Center

Irvine, California, 92697, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Rigshospitalet, University of Copenhagen

Copenhagen, Denmark

Location

Foundation IRCCS Neurological Institute Carlo

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral; Muscular Dystrophies, Limb-Girdle

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: June 30, 2016
• First Posted: July 19, 2016
• Study Start: July 13, 2016
• Primary Completion: April 18, 2017
• Study Completion: April 18, 2017
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DK (1); US (3)