Clinical trial NCT02579239: Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Limb-Girdle Muscular Dystrophies
Facioscapulohumeral Muscular Dystrophy
Keywords: LGMD2B
FSHD
Lead sponsor: aTyr Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to End of Study (up to Week 25)
measure: Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE
timeFrame: Up to End of Study (up to Week 25)
measure: Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
timeFrame: Up to End of Study (up to Week 25)
measure: Number of Participants With a Clinical Laboratory Abnormality Leading to an AE
timeFrame: Up to End of Study (up to Week 25)
measure: Number of Participants With Vital Sign Abnormality Resulting in a TEAE
timeFrame: Up to End of Study (Up to Week 25)
Secondary outcomes:
measure: Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
timeFrame: Baseline, Week 14
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine, ALS and Neuromuscular Center
state: California
city: Baltimore
country: United States
facility: Kennedy Krieger Institute; The Johns Hopkins University School of Medicine
state: Maryland
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: Marseille
country: France
facility: Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
city: Paris
country: France
facility: Institut de Myologie, Hôpital Pitié-Salpêtrière
Study officials:
References: