An Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Fascioscapulohumeral Muscular Dystrophy

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2016-000624-25-DK
• Date of registration: 19/04/2016
• Prospective Registration: Yes
• Primary sponsor: aTyr Pharma, Inc.
• Public title: An Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Fascioscapulohumeral Muscular Dystrophy
• Scientific title: An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Fascioscapulohumeral Muscular Dystrophy
• Date of first enrolment: 22/06/2016
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000624-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Denmark, Italy, United States

Contacts

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

• Name: Clinical Trial Operations
• Affiliation: Voisin Consulting

Key inclusion & exclusion criteria

Inclusion criteria:
1. Enrolled in and completed the treatment period in the parent study.
2. Demonstrated, in the Investigator’s opinion, acceptable tolerability of ATYR1940.
3. In the Investigator’s opinion, patient 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 Investigator’s and Sponsor’s opinion, a suitable candidate for continued ATYR1940 treatment.
5. Provide written informed consent after the nature of the study has been explained and prior to the performance of any research-related procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range: 2
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. At any time during participation in the parent study, met a ATYR1940 discontinuation criterion, including, but not limited to:
- Jo-1 antibody (Ab) levels =1.5 U/mL.
- Clinical evidence of a generalized infusion-related reaction (IRR).
- Clinical evidence of a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) =Grade 2, study-drug-related serious adverse event (SAE).
- Pregnancy.
- Progression of disease that, in the opinion of the Investigator, precluded further participation in the study.
- Withdrawal of consent.
- Other findings that, at the discretion of the Investigator and/or Sponsor, indicated that study drug administration should be discontinued.
2. 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 (e.g., insulin-like growth factor, growth hormone) or activity (e.g., 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).
3. Patient planned to receive any vaccination during study participation.
4. Abnormal baseline findings, medical condition(s), or laboratory findings that, in the Investigator’s opinion, might jeopardize the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
5. 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.
6. 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.
7. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy
MedDRA version: 19.0 Level: PT Classification code 10064087 Term: Facioscapulohumeral muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: ATYR1940
Product Code: ATYR1940
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not available yet
Current Sponsor code: ATYR1940
Other descriptive name: ATYR1940
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: To explore the biological and pharmacodynamic (PD) activity of ATYR1940 in patients with LGMD2B and FSHD, based on changes in:
• Serum-based muscle biomarkers.
• Inflammatory immune state in peripheral blood.
• Muscle disease and muscle disease burden, based on skeletal muscle MRI.
• Skeletal muscle strength.
• Upper and lower extremity muscle function.
• Quality of life measures.

Primary end point(s): Safety and tolerability:
• Incidence of treatment-emergent adverse events (TEAEs) and SAEs overall and by intensity
• Changes from baseline in:
- Safety laboratory test results
- Electrocardiogram (ECG) findings
- Vital signs measurements
- Pulmonary evaluations (pulmonary function tests [PFTs] and pulse oximetry)
- Incidence and level of anti-drug antibodies (ADA) titers and Jo-1 Ab levels
• Exploratory characterization of immune response to ATYR1940

Main Objective: To evaluate the safety, tolerability, and immunogenicity of long-term treatment with intravenous (IV) ATYR1940 in patients with limb girdle muscular dystrophy 2B (LGMD2B) or fascioscapulohumeral muscular dystrophy (FSHD) previously enrolled in clinical study ATYR1940-C-003 (Stage 1 only) or ATYR1940-C-004.

Timepoint(s) of evaluation of this end point: Safety and tolerability:
- Adverse events & vital signs & pulse oximetry & Jo-1 Ab: at week 1, every week and at 1, 4 and 12-week follow-up
- Lab test results & ADA: at week 1, every month and at 1, 4 and 12-week follow-up
- ECG: at week 1, every month and at 1 and 4-week follow-up
- Pulmonary function tests: at week 1, every 6 weeks or every 3 months and at 4-week follow-up

Secondary Outcome(s)

Secondary end point(s): Muscle strength and function:
• Changes from baseline in the following clinical parameters:
- Muscle disease burden on lower extremity skeletal muscle MRI
- Muscle strength, based on manual muscle testing (MMT)
- Upper and lower extremity muscle function, based on the Brooke and Vignos scales, respectively

Pharmacodynamics (exploratory):
• Changes in muscular-dystrophy-related inflammatory immune state in peripheral blood, as assessed by:
- Circulating immune proteins, such as cytokines
- Ex vivo inflammatory immune protein (including cytokines) release from peripheral blood mononuclear cells (PBMCs)
- Immunophenotyping of circulating PBMCs
• Changes in serum- and/or plasma-based muscle biomarkers

Quality of life (exploratory):
• INQoL questionnaire
• For patients with FSHD, the FSHD-specific Health Inventory (FSHD-HI) questionnaire

Systemic exposure:
• Sparse pharmacokinetic (PK) sampling

Timepoint(s) of evaluation of this end point: Muscle strength and function:
- Surveillance skeletal muscle MRI: at week 1, every 3 months and at 12-week follow-up
- MMT & Upper and lower extremity muscle function: at week 1, every 3 months and at 1-week follow-up

Pharmacodynamics:
- PBMCs & muscle biomarkers: at week 1, every 3 months and at 1 and 4-week follow-up

Quality of life:
INQoL & FSHD-HI: at week 1, every 3 months and at 1 and 12-week follow-up

Systemic exposure:
- Serum ATYR1940 concentrations: at week 1, every 6 weeks and at 1-week follow-up

Secondary ID(s)

122045

ATYR1940-C-006

Source(s) of Monetary Support

aTyr Pharma, Inc.