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

Primary Purpose

Limb-Girdle Muscular Dystrophies, Facioscapulohumeral Muscular Dystrophy

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ATYR1940
Placebo
Sponsored by
aTyr Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Limb-Girdle Muscular Dystrophies focused on measuring LGMD2B, FSHD

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provided informed consent
  • Investigator's opinion, patient is willing and able to complete all study procedures and comply with the study visit schedule.

Patients with LGMD2B:

  • Established, genetically confirmed diagnosis of LGMD2B.
  • Either the presence of a STIR-positive muscle on lower extremity skeletal muscle MRI, or, if no STIR-positive muscles, meets muscle biomarker criteria.

Patients 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 4 weeks 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 patient's ability to complete the study protocol.
  • Muscle biopsy within 30 days before baseline.

Sites / Locations

  • University of California, Irvine, ALS and Neuromuscular Center
  • Kennedy Krieger Institute; The Johns Hopkins University School of Medicine
  • OSU Wexner Medical Center
  • Rigshospitalet, University of Copenhagen
  • Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
  • Institut de Myologie, Hôpital Pitié-Salpêtrière

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A - FSHD

Group B - LGMD2B and FSHD

Arm 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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.
Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE
ECG parameters that were evaluated included heart rate, PR, and QR and QT intervals. A clinically significant ECG abnormality was based upon the Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
Pulmonary evaluations included pulmonary function tests and pulse oximetry. Clinically significant changes were to be reported as adverse events. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Number of Participants With a Clinical Laboratory Abnormality Leading to an AE
Laboratory parameters included hematology (hematocrit, hemoglobin, red blood cell count, white blood cell count with differential [neutrophils, lymphocytes, monocytes, eosinophils, basophils], and platelet count); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total protein, sodium, potassium, bicarbonate, calcium, chloride, magnesium, inorganic phosphate, creatine kinase, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, and cholesterol [(nonfasting]); urinalysis (color, pH, specific gravity, protein, glucose, ketones, and blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Number of Participants With Vital Sign Abnormality Resulting in a TEAE
The vital sign parameters that were evaluated included heart rate, systolic and diastolic blood pressure, and respiration rate as well as temperature. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Secondary Outcome Measures

Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.

Full Information

First Posted
September 28, 2015
Last Updated
September 26, 2023
Sponsor
aTyr Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02579239
Brief Title
Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
Acronym
FSHD
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
November 30, 2015 (Actual)
Primary Completion Date
October 5, 2016 (Actual)
Study Completion Date
October 5, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
aTyr Pharma, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limb-Girdle Muscular Dystrophies, Facioscapulohumeral Muscular Dystrophy
Keywords
LGMD2B, FSHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A - FSHD
Arm Type
Experimental
Arm 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.
Arm Title
Group B - LGMD2B and FSHD
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
ATYR1940
Intervention Description
Concentrate for solution for infusion
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Concentrate for solution for infusion
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.
Time Frame
Up to End of Study (up to Week 25)
Title
Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE
Description
ECG parameters that were evaluated included heart rate, PR, and QR and QT intervals. A clinically significant ECG abnormality was based upon the Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time Frame
Up to End of Study (up to Week 25)
Title
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
Description
Pulmonary evaluations included pulmonary function tests and pulse oximetry. Clinically significant changes were to be reported as adverse events. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time Frame
Up to End of Study (up to Week 25)
Title
Number of Participants With a Clinical Laboratory Abnormality Leading to an AE
Description
Laboratory parameters included hematology (hematocrit, hemoglobin, red blood cell count, white blood cell count with differential [neutrophils, lymphocytes, monocytes, eosinophils, basophils], and platelet count); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total protein, sodium, potassium, bicarbonate, calcium, chloride, magnesium, inorganic phosphate, creatine kinase, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, and cholesterol [(nonfasting]); urinalysis (color, pH, specific gravity, protein, glucose, ketones, and blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time Frame
Up to End of Study (up to Week 25)
Title
Number of Participants With Vital Sign Abnormality Resulting in a TEAE
Description
The vital sign parameters that were evaluated included heart rate, systolic and diastolic blood pressure, and respiration rate as well as temperature. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time Frame
Up to End of Study (Up to Week 25)
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
Description
MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.
Time Frame
Baseline, Week 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
University of California, Irvine, ALS and Neuromuscular Center
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
Kennedy Krieger Institute; The Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
OSU Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Rigshospitalet, University of Copenhagen
City
Copenhagen
Country
Denmark
Facility Name
Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Institut de Myologie, Hôpital Pitié-Salpêtrière
City
Paris
Country
France

12. IPD Sharing Statement

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

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