Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)

aTyr Pharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Facioscapulohumeral Muscular Dystrophy; Limb-Girdle Muscular Dystrophies

Treatments: Biological: Placebo; Biological: ATYR1940

Study type: Interventional

Funder types: Industry

Identifiers

NCT02579239

2015-001910-88 (EudraCT Number)

ATYR1940-C-004

Details and patient eligibility

About

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

Enrollment: 18 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

18 participants in 2 patient groups

Group A - FSHD

Experimental group

Description:

Participants with FSHD will receive single dose of placebo intravenous (IV) infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 milligrams/kilograms (mg/kg) once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Treatment:

Biological: Placebo

Biological: ATYR1940

Group B - LGMD2B and FSHD

Experimental group

Description:

Participants with LGMD2B and FSHD will receive single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Treatment:

Biological: Placebo

Biological: ATYR1940