The Safety and Biological Activity of ATYR1940 in Patients With Limb Girdle or Facioscapulohumeral Muscular Dystrophies (FSHD)

• ClinicalTrials.gov Identifier: NCT02579239
• Recruitment Status: Completed
• First Posted: October 19, 2015
• Last Update Posted: May 17, 2017
• Sponsor: aTyr Pharma, Inc.
• Information provided by (Responsible Party): aTyr Pharma, Inc.

Study Description

Brief Summary:

The purpose of this study is to assess the safety and biological activity of ATYR1940 in patients with Limb Girdle (LGMD2B) or Facioscapulohumeral Muscular Dystrophy (FSHD).

Condition or disease	Intervention/treatment	Phase
Limb-Girdle Muscular Dystrophies; Facioscapulohumeral Muscular Dystrophy	Biological: ATYR1940; Biological: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 5, 2015
• Actual Primary Completion Date: October 5, 2016
• Actual Study Completion Date: October 5, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: ATYR1940; Intrapatient dose escalation of intravenous ATYR1940 administered twice weekly at doses of 0.3, 1.0, or 3.0 mg/kg for up to 12 weeks.	Biological: ATYR1940; Intrapatient dose escalation of intravenous ATYR1940 administered twice weekly at doses of 0.3, 1.0, or 3.0 mg/kg for up to 12 weeks.
Placebo Comparator: Placebo; Patients will receive an initial infusion of placebo at Week 1, supplied as normal saline and administered via IV infusion over a 30-minute period.	Biological: Placebo; Patients will receive an initial infusion of placebo at Week 1, supplied as normal saline and administered via IV infusion over a 30-minute period.

Outcome Measures

Primary Outcome Measures :

1. Tolerability Primary Outcome Measure - incidence of treatment-emergent adverse events (AEs) and serious adverse events overal (SAEs) overall and by intensity [ Time Frame: 12 weeks ]
   Incidences of Adverse Events (AEs), including serious and severe AEs
2. Safety Primary Outcome Measure - change from Baseline in safety laboratory test results [ Time Frame: 12 weeks ]
   Change from Baseline in safety laboratory test results (clinical chemistry, hematology, and urinalysis)
3. Safety Primary Outcome Measure - change from Baseline in ECG [ Time Frame: 12 weeks ]
   Change from Baseline in 12-lead ECG findings
4. Safety Primary Outcome Measure - change from Baseline in vital signs measurements and pulmonary evaluations [ Time Frame: 12 week ]
   Change from Baseline in vital signs measurements (blood pressure, pulse, respiratory rate, and body temperature) and pulmonary evaluations (PFTs and pulse oximetry)

Secondary Outcome Measures :

1. Pharmacodynamic Additional Outcome Measure - changes in muscular dystrophy-related inflammatory immune state [ Time Frame: 12 weeks ]
   Effects assessed by changes in muscular dystrophy-related inflammatory immune state in peripheral blood
2. Pharmacodynamic Additional Outcome Measure - changes in serum- and/or plasma-based muscle biomarkers. [ Time Frame: 12 weeks ]
   Serum-based muscle biomarkers

Eligibility Criteria

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

Criteria

Inclusion Criteria:

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

Patients with LGMD2B:

• Established, genetically confirmed diagnosis of LGMD2B.
• Either the presence of a STIR-positive muscle on lower extremity skeletal muscle MRI, or, if no STIR-positive muscles, meets muscle biomarker criteria.

Patients 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 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 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 patient's ability to complete the study protocol.
• Muscle biopsy within 30 days before baseline.

Contacts and Locations

Locations

United States, California

University of California, Irvine, ALS and Neuromuscular Center

Irvine, California, United States, 92697

United States, Maryland

Kennedy Krieger Institute; The Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21205

United States, Ohio

OSU Wexner Medical Center

Columbus, Ohio, United States, 43210

Denmark

Rigshospitalet, University of Copenhagen

Copenhagen, Denmark

France

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

Marseille, France, 13385

Institut de Myologie, Hôpital Pitié-Salpêtrière

Paris, France

Sponsors and Collaborators

aTyr Pharma, Inc.

Investigators

• Study Director: Kelly Blackburn; aTyr Pharma

More Information

• Responsible Party: aTyr Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT02579239
• Other Study ID Numbers: ATYR1940-C-004; 2015-001910-88 ( EudraCT Number )
• First Posted: October 19, 2015
• Last Update Posted: May 17, 2017
• Last Verified: May 2017

Keywords provided by aTyr Pharma, Inc.:

LGMD2B; FSHD

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Facioscapulohumeral; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn