Evaluate Safety and Biological Activity of ATYR1940 in Patients With Early Onset Facioscapulohumeral Muscular Dystrophy (FSHD)

Study Description

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Brief Summary:

The purpose of this study is to assess the safety and biological activity of ATYR1940 in patients with early onset facioscapulohumeral muscular dystrophy (FSHD).

Condition or disease	Intervention/treatment	Phase
Facioscapulohumeral Muscular Dystrophy (FSHD)	Biological: ATYR1940; Biological: Placebo	Phase 1; Phase 2

Detailed Description:

A Phase 1b/2 open-label, intrapatient dose escalation study aiming to evaluate the safety, tolerability, immunogenicity, biological and pharmacodynamic activity of intravenous ATYR1940, administered once weekly for 12 weeks, in early onset FSHD patients with signs or symptoms prior to 10 years of age. In Stage 1, up to 8 patients between the ages of 16 and 25 years will be enrolled. Stage 2 of enrollment will include patients with early onset FSHD between the ages of 12 and 15 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 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 Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy
Actual Study Start Date :	March 30, 2016
Actual Primary Completion Date :	December 13, 2016
Actual Study Completion Date :	February 14, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: ATYR1940; Intrapatient dose escalation ATYR1940: ATYR1940 will be administered as an IV infusion at doses of 0.3, 1.0, and 3.0 mg/kg for up to 12 Weeks. The dose level in this study will not exceed 3.0 mg/kg.	Biological: ATYR1940; ATYR1940 will be administered as an IV infusion at doses of 0.3, 1.0, and 3.0 mg/kg using intrapatient dose escalation. The dose level in this study will not exceed 3.0 mg/kg
Placebo Comparator: Placebo; An initial IV infusion of placebo will be supplied as normal saline, and administered over a 30-minute period at Week 1.	Biological: Placebo; An initial IV infusion of placebo will be supplied as normal saline, and administered over a 30-minute period at Week 1.

Outcome Measures

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Primary Outcome Measures :

1. Incidences of Treatment-Emergent adverse events and serious adverse events [ Time Frame: 12 weeks ]
   Incidences of adverse events including serious and severe adverse events overall and by intensity
2. Changes from Baseline in safety laboratory test results [ Time Frame: Changes from Baseline after 12 weeks ]
   Changes from Baseline in safety laboratory test results
3. Changes from Baseline in pulmonary evaluation [ Time Frame: Changes from Baseline after 12 week ]
   Change from Baseline in pulmonary evaluation
4. Changes from Baseline in visual assessment [ Time Frame: Changes from Baseline after 12 weeks ]
   Changes in Baseline in visual acuity
5. Changes from Baseline in hearing [ Time Frame: Changes from Baseline after 12 weeks ]
   Safety Primary Outcome Measure - Changes from Baseline in hearing based on audiometry

Secondary Outcome Measures :

1. Immunogenicity Outcome Measure - Incidence and level of ADA [ Time Frame: 12 weeks ]
   Incidence and level of ADA titers
2. Immunogenicity Outcome Measure - Incidence and level of Jo-1 Ab [ Time Frame: 12 weeks ]
   Incidence and level of Jo-1 Ab titers
3. Immunogenicity Outcome Measure - Incidence of infusion reactions [ Time Frame: 12 weeks ]
   Incidence of infusion reactions

Other Outcome Measures:

1. Pharmacodynamic Additional Outcome Measure - Changes in FSHD-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 from baseline clinical parameters [ Time Frame: 12 weeks ]
   Changes from baseline in muscle strength based on manual muscle strength

Eligibility Criteria

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Ages Eligible for Study:	12 Years to 25 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Established, genetically confirmed diagnosis of FSHD.
• Onset of FSHD signs or symptoms prior to 10 years of age, as documented in the patient's medical record or based on patient or family report.
• Provide written informed consent or assent
• In the Investigator's opinion, patient is willing and able to complete all study procedures and comply with the weekly study visit schedule.

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

Contacts and Locations

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Locations

United States, California
Stanford University
Stanford, California, United States, 94305
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Ohio
OSU Wexner Medical Center
Columbus, Ohio, United States, 43210
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
France
Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
Marseille, France, 13385
Institut de Myologie
Paris, France, 75651
Italy
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Milano, Italy, 20133

Sponsors and Collaborators

aTyr Pharma, Inc.

Investigators

Study Director:	Kelly Blackburn	aTyr Pharma

More Information

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Responsible Party:	aTyr Pharma, Inc.
ClinicalTrials.gov Identifier:	NCT02603562 History of Changes
Other Study ID Numbers:	ATYR1940-C-003; 2014-003346-27 ( EudraCT Number )
First Posted:	November 13, 2015
Last Update Posted:	May 17, 2017
Last Verified:	May 2017

Keywords provided by aTyr Pharma, Inc.:

FSHD

Additional relevant MeSH terms:

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