Clinical trial NCT02836418: Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
Official title: An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Patients With Limb Girdle and Facioscapulohumeral Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Facioscapulohumeral Muscular Dystrophy
Limb Girdle Muscular Dystrophy
Keywords: FSHD
LGMD
Lead sponsor: aTyr Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-19
Enrollment: 8
Sex: ALL
Minimum age (years): 16
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: ATYR1940-C-006 is a multi-national, multicenter study being conducted at centers in the United States (US) and Europe who participated in Study ATYR1940-C-003 (Stage 1 only) or Study ATYR1940-C-004 (that is, the parent studies).

Detailed description: Study ATYR1940-C-006 is a multi-national, multi-center, open-label extension study designed to evaluate the long-term safety, effects on muscle, and pharmacodynamics of ATYR1940 in participants with Limb-girdle muscular dystrophy (LGMD) or FSHD previously treated in the Study ATYR1940-C-003 (Stage 1 only) or Study ATYR1940-C-004 that is, the parent studies). This study will be conducted at the same study centers at which participants were enrolled in the parent studies.

Participants who completed the treatment period in the parent study and, in the Investigator's opinion, demonstrated acceptable tolerability of ATYR1940, are considered by the Investigator to be compliant with ATYR1940 and the study procedures, and do not meet any criterion for ATYR1940 discontinuation are eligible for participation in the current study, contingent upon Investigator and participant agreement to continue ATYR1940 treatment.

For the first 12 weeks in this extension study, participants will receive ATYR1940 at the highest tolerated dose received in the parent study; no dose adjustments are allowed during this 12-week period. After 12 weeks, if the participant is demonstrating good tolerability, the ATYR1940 dose may be increased on a participant-specific basis at the Investigator's discretion, in consultation with the Sponsor and Medical Monitor. ATYR1940 dose increases to \>3.0 mg/kg are not permissible.

All participants will receive ATYR1940 on a weekly basis in this study, regardless of the frequency of dosing in the parent study. ATYR1940 will be administered via intravenous (IV) infusion over 90 minutes. If medically indicated, the infusion duration and volume may be adjusted at the Investigator's discretion in consultation with the Medical Monitor and Sponsor.

Eligibility criteria: Inclusion Criteria:

1. Enrolled in and completed the treatment period in the parent study.
2. Demonstrated, in the Sponsor's and Investigator's opinions, acceptable tolerability of ATYR1940.
3. In the Investigator's opinion, participant has shown acceptable compliance with ATYR1940 and the study procedures in the parent study and is willing and able to comply with all procedures in the current study.
4. Is, in the opinion of the Investigator and Sponsor, a suitable candidate for continued ATYR1940 treatment.
5. Provide written informed consent or assent after the nature of the study has been explained and prior to the performance of any research-related procedures.

Exclusion Criteria:

1. Is expected to require treatment with curcumin or systemic albuterol (intermittent inhaled albuterol is permissible) during study participation; or use of a product that putatively enhances muscle growth (for example, insulin-like growth factor, growth hormone) or activity (for example, Coenzyme Q, Coenzyme A, creatine, L-carnitine) on a chronic basis; or statin treatment initiation or significant adjustment to statin regimen (stable, chronic statin use is permissible).
2. Planned to receive any vaccination during study participation.
3. Abnormal baseline findings, medical condition(s), or laboratory findings that, in the Investigator's opinion, might jeopardize the participant's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
4. Evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention, other treatment, or may not allow safe participation.
5. If female and of childbearing potential (premenopausal and not surgically sterile), has a positive pregnancy test at entry or is unwilling to use contraception from the time of entry through the 3-month Follow-up visit. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device.
6. If male, is unwilling to use a condom plus spermicide during sexual intercourse from the time of entry through the 1 month Follow-up visit.

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 approximately Week 39)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA)
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL)
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Number of Participants With a Clinical Laboratory Abnormality Leading to an AE
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Number of Participants With Vital Sign Abnormality Resulting in a TEAE
timeFrame: Up to End of Study (up to approximately Week 39)
measure: Change From Baseline in Manual Muscle Testing (MMT) Score at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Creatinine Kinase at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine, ALS and Neuromuscular Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: Milan
country: Italy
facility: Foundation IRCCS Neurological Institute Carlo
Study officials:
References: