A Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Facioscapulohumeral Muscular Dystrophies

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2015-001910-88-DK
• Date of registration: 30/06/2015
• Prospective Registration: Yes
• Primary sponsor: aTyr Pharma, Inc.
• Public title: A Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Facioscapulohumeral Muscular Dystrophies
• Scientific title: An Open-Label, Intrapatient Dose Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients with Limb Girdle and Facioscapulohumeral Muscular Dystrophies
• Date of first enrolment: 17/12/2015
• Target sample size: 16
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001910-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 1
• 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, France, 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. Male or female aged 18 to 75 years, inclusive.
2. Provided written informed consent.
3. In the Investigator’s opinion, is willing and able to complete all study procedures and comply with the study visit schedule.
4. Established genetically confirmed diagnosis of LGMD2B or FSHD.
5. Either the presence of a STIR positive muscle with limited fatty infiltration, as determined by the Fischer scoring system, on MRI (FHSD) or an elevated muscle marker (LGMD2B)
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 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Currently receiving treatment with an immunomodulatory agent or history of such treatment, including targeted biological therapies (e.g., etanercept, omalizumab) or corticosteroids within the 3 months before baseline; or high-dose non-steroidal anti-inflammatory agents within 2 weeks before baseline.
2. Currently receiving curcumin or albuterol or requires such treatment during study participation; use of a product that putatively enhances muscle growth or activity on a chronic basis within 30 days before baseline; or statin treatment initiation or significant adjustment to statin regimen within 3 months before baseline.
3. Use of an investigational product or device (other than a mobility assistance device) within 30 days before baseline.
4. History of severe restrictive or obstructive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence of active lung disease on screening chest radiograph.
5. History of anti-synthetase syndrome, prior Jo-1 Ab-positivity, or Jo 1 Ab level =0.6 U/mL on screening.
6. Acute or clinically relevant Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection or re-activation.
7. Chronic infection, such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) or a history of tuberculosis.
8. Vaccination within 8 weeks before baseline or vaccination is planned during study participation.
9. Symptomatic cardiomyopathy or severe cardiac arrhythmia (including bradyarrythmias), that may, in the Investigator’s opinion, limit the patient’s ability to complete the study protocol.
10. Gamma-glutamyl transferase (GGT) or serum creatinine levels >2× the upper limit of normal.
11. Muscle biopsy within 30 days before baseline.


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

Health Condition(s) or Problem(s) studied

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

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
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Safety and tolerability
• Incidence of treatment-emergent AEs and SAEs overall and by intensity.
• Changes from baseline in safety laboratory test results.
• Changes from baseline in ECG findings.
• Changes from baseline in vital signs measurements.
• Changes from baseline in pulmonary evaluations (PFTs and pulse oximetry).

Immunogenicity
• Incidence and level of ADA titers and Jo-1 Ab.
• Exploratory characterization of immune response to ATYR1940.

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 burden.
• Skeletal muscle strength.
• Upper and lower extremity muscle function.
• Quality of life measures.

Main Objective: To evaluate the safety, tolerability, and immunogenicity of the weekly and twice weekly intravenous (IV) administration of ATYR1940, at doses of 0.3, 1.0, and 3.0 mg/kg, to patiens with Dysferlinopathy (Limb Girdle Muscular Dystrophy 2B [LGMD2B]) and Facioscapulohumeral Muscular Dystrophy (FSHD).

Timepoint(s) of evaluation of this end point: Safety and tolerability
- AEs & vital signs: throughout the study
- Safety laboratory test results: Screening, weeks 1, 2 4, 6, 8, 10, 12, 14, 17 and 25 (follow-up period)
- ECG: Screening, weeks 2, 4, 6 and 10 to 14 (follow-up period)
- Pulmonary function tests: Screening, week 5, 8, 13 and 17 (follow-up period)
- Pulse oximetry: weeks 1 to 13

Immunogenicity:
- Level of ADA titers: Screening, weeks 4, 6, 8 and 10 to 25 (follow-up period)
- Level of Jo-1 Ab: Screening, weeks 3 to 13, 14, 17 and 25 (follow-up period)
- Plasma complement levels: weeks 1, 4, 8, 11 and 14 (follow-up period)
- Serum complement and tryptase levels: weeks 1 and 14 (follow-up period)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Pharmacodynamics:
- PBMCs: Screening, weeks 1, 9, 13 and 14 (follow-up period)
- Serum/plasma biomarkers: weeks 1, 2, 4, 6, 9, 10, 13 and 14 (follow-up period)
- Skeletal muscle MRI: Screening, weeks 9, 13 and 14 (follow-up period)
- MMT & Upper and lower extremity function: Screening, weeks 7, 10 and 14 (follow-up period)
- INQoL: Screening, weeks 7, 14 and 25 (follow-up period)
- Physical activity monitor: weeks 1 to 17 (daily)

Secondary end point(s): Pharmacodynamics
• Changes in muscular-dystrophy-related inflammatory immune state in peripheral blood.
• Changes in serum- and/or plasma-based muscle biomarkers.
• Changes from baseline in the following clinical parameters:
- Lower extremity skeletal muscle MRI.
- Muscle strength, based on MMT.
- Upper and lower extremity muscle function, based on the Brooke and Vignos scales, respectively.
- Physical activity monitoring.
- Quality of life based on the INQoL questionnaire.

Secondary ID(s)

ATYR1940-C-004

122045

Source(s) of Monetary Support

aTyr Pharma, Inc.