A Study to Evaluate the Long-Term Safety, Tolerability, Biological Activity, and Exposure of ATYR1940 in Adult Patients with Genetic Myopathy

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2015-001912-36-NL
• Date of registration: 22/06/2015
• Prospective Registration: Yes
• Primary sponsor: aTyr Pharma, Inc.
• Public title: A Study to Evaluate the Long-Term Safety, Tolerability, Biological Activity, and Exposure of ATYR1940 in Adult Patients with Genetic Myopathy
• Scientific title: An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, Biological Activity, and Systemic Exposure of ATYR1940 in Adult Patients with Facioscapulohumeral Muscular Dystrophy (FSHD)
• Date of first enrolment: 04/08/2015
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001912-36
• 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

Italy, Netherlands, 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 =Cohort 2 and completed the double-blind treatment period in the parent study.
2. Demonstrated, in the Investigator’s opinion, acceptable tolerability of study drug.
3. In the Investigator’s opinion, patient has shown acceptable compliance with study drug 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 study drug treatment.
5. Provided 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? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
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 study drug discontinuation criterion, including, but not limited to:
a. Jo-1 Ab levels =1.5 U/mL.
b. Clinical evidence of a generalized infusion-related reaction (IRR).
c. Clinical evidence of a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) =Grade 2, study-drug-related SAE.
d. Pregnancy.
e. Progression of disease that, in the opinion of the Investigator, precluded further participation in the study.
f. Withdrawal of consent.
g. 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. 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 1-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

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

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

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)

Main Objective: Evaluate the safety, tolerability, and immunogenicity of long-term treatment with intravenous (IV) ATYR1940 in adult patients with facioscapulohumeral muscular dystrophy (FSHD) previously enrolled in clinical study ATYR1940-C-002

Primary end point(s): Safety and tolerability:
• Change from baseline in physical examination, including neurological examination.
• Incidence of AEs, including serious and severe AEs.
• Change from baseline in safety laboratory test results.
• Change from baseline in electrocardiogram (ECG) findings.
• Change from baseline in vital sign measurements and pulmonary evaluations (pulmonary function tests and pulse oximetry).
• Anti-drug antibody (ADA) titers and Jo-1 antibody levels.
• Exploratory characterization of immune response to ATYR1940.

Secondary Objective: • Evaluate the effects of long-term ATYR1940 treatment on clinically relevant measures of muscle strength and function, including: Quantitative Muscle Testing (QMT) and Manual muscle testing (MMT), as determined by the Investigator
• Evaluate the effects of long-term ATYR1940 treatment on patient-reported quality of life (QoL)
• Evaluate the effects of long-term ATYR1940 treatment on muscle disease burden, based on skeletal muscle magnetic resonance imaging (MRI)
• Explore biological and pharmacodynamic (PD) changes in the inflammatory immune state in peripheral blood
• Determine the long-term systemic exposure to ATYR1940 through pharmacokinetic (PK) sampling

Timepoint(s) of evaluation of this end point: Physical Exam: at eligibility check, W4, every 3M and at 1 and 4-week FU
AEs: weekly and at 1, 4 and 12-week FU
Safety lab tests: at eligibility check, W1 to W4, monthly and at 1, 4 and 12-week FU
ECG: at W1, W2, W4, every 3M and at 1 and 4-week FU
Vital signs: at eligibility check, weekly and at 1, 4 and 12-week FU
Pulmonary function tests: at W1, every 3M and at 4-week FU
Pulse Oximetry: at W1 to W4, every 3M and at 1, 4 and 12-week FU
Jo-1 Ab: at eligibility check, weekly from W2 and at 1, 4 and 12-week FU
ADA: at eligibility check, W2, W3, every 3M and at 1, 4 and 12-week FU
Plasma complement factors: at W1, W3, W16, every 3M starting at W24 and at 1-week FU
Serum complement and tryptase levels: at W1, W16, every 3M starting at W24 and at 1-week FU

Secondary Outcome(s)

Secondary end point(s): Muscle strength and function:
• Muscle strength, based on Quantitative muscle testing (QMT) and Manual muscle testing (MMT)
• Lower extremity muscle function based on the Vignos scale

Quality of life:
• INQoL questionnaire
• FSHD-HI questionnaire
• Additional measures of quality of life (e.g., sleep status)

Pharmacodynamic effects of ATYR1940:
• Muscle disease burden on lower extremity skeletal muscle MRI
• Changes in FSHD-related inflammatory immune state in peripheral blood

Systemic exposure:
• PK sampling

Timepoint(s) of evaluation of this end point: QMT & MMT & Vignos scale & INQoL & sleep status: at eligibility check, every 3M and at 1-week FU
FSHD-HI: at eligibility check and every 3M
Skeletal Muscle Surveillance MRI: at eligibility check, at M3 and then every 6M and at 4-week FU
PBMCs & biomarkers: at eligibility check, at W4, every 3M and at 1 and 4-week FU
Pharmacokinetics: at W1 to W4, every 3M and at 1-week FU

Secondary ID(s)

ATYR1940-C-005

122045

Source(s) of Monetary Support

aTyr Pharma, Inc.