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A Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATYR1940 in Adult Patients with Molecularly Defined Genetic Muscular Dystrophies

Completed
Conditions
Facioscapulohumeral muscular dystrophy
genetic myopathy
10028396
Registration Number
NL-OMON42284
Lead Sponsor
aTyr Pharma, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
16
Inclusion Criteria

1. Patient is a male or female aged 18 to 65 years, inclusive.;2. Patient has an established, genetically-confirmed, diagnosis of FSHD with clinical findings meeting existing criteria.;3. Patient has provided written informed consent after the nature of the study has been explained and prior to the performance of any research-related procedures.;4. Cohorts >=2 only: Patient has imaging findings meeting defined criteria for muscle inflammation in at least 1 skeletal muscle (as per MRI Procedural Manual).

Exclusion Criteria

1. Patient is currently receiving treatment with an immunomodulatory agent or has a history of such treatment, including targeted biological therapies (e.g., etanercept, omalizumab) within the 3 months before Baseline; corticosteroids within 4 weeks before Baseline; or high-dose non-steroidal anti-inflammatory agents (NSAIDs) (either chronic or intermittent) within 2 weeks before Baseline.;2. Patient has evidence of an alternative diagnosis other than FSHD, based on prior muscle biopsy or genetic test findings.;3. Patient has a presumptive diagnosis of FSHD, based on clinical assessment, but does not yet have genetic confirmation of the diagnosis.;4. Patient has a history of obstructive or restrictive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for interstitial lung disease on Screening chest radiograph.;5. Patient has a history of anti-synthetase syndrome, prior Jo-1 antibody (Ab)-positivity, or has a positive or equivocally positive Jo 1 Ab test result during Screening.;6. Patient has symptomatic cardiomyopathy or severe cardiac arrhythmia that may, in the Investigator*s opinion, limit the patient*s ability to complete the study protocol.;7. Patient has evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention or other treatment or may not allow safe participation.;8. Patient has used any investigational product or device (other than a mobility assistance device) within 30 days before Baseline.;9. Patient underwent muscle biopsy within 30 days before Baseline.;10. If female and of childbearing potential (premenopausal and not surgically sterile), patient has a positive pregnancy test at Screening or is unwilling to use contraception.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Safety and tolerability will be evaluated by the following:<br /><br>• Change from Baseline of physical examination.<br /><br>• Incidence of AEs.<br /><br>• Change from Baseline in safety laboratory test results.<br /><br>• Change from Baseline in ECG findings.<br /><br>• Change from Baseline in vital sign measurements and pulmonary evaluations.<br /><br>• Antibody test results.<br /><br>• Incidence of infusion reactions and infusion site examination findings.<br /><br><br /><br>The following PK parameters will be determined or calculated from the drug<br /><br>concentration time data as follows using WinNonlin:<br /><br>• Standard PK parameters (Cmax, tmax, t1/2, etc).</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>The PD effects of ATYR1940 will be evaluated by the following:<br /><br>• Changes in FSHD-related inflammatory immune state in peripheral blood and<br /><br>muscle.<br /><br>• Changes in the following clinical parameters.</p><br>
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