Back to resultsEvaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy (FSHD)
Primary Purpose
Facioscapulohumeral Muscular Dystrophy (FSHD)
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ATYR1940
Sponsored by
About this trial
This is an interventional treatment trial for Facioscapulohumeral Muscular Dystrophy (FSHD) focused on measuring FSHD
Eligibility Criteria
Inclusion Criteria:
- Established, genetically confirmed diagnosis of FSHD.
- Onset of FSHD signs or symptoms prior to 10 years of age, as documented in the patient's medical record or based on patient or family report.
- Provide written informed consent or assent
- In the Investigator's opinion, patient is willing and able to complete all study procedures and comply with the weekly study visit schedule.
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 or activity 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 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
- Stanford University
- University of Iowa Children's Hospital
- OSU Wexner Medical Center
- University of Utah
- Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
- Institut de Myologie
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ATYR1940
Arm Description
Participants received ATYR1940 intravenous (IV) infusion at doses of 0.3, 1.0, and 3.0 milligrams/kilograms (mg/kg) once weekly using intraparticipant dose escalation for 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. AEs were 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. SAEs were 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, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, 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 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]); and 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 an Ocular Abnormality Leading to a TEAE
Ocular parameters included vitreous, retina, macula, choroid, optic nerve, and optic nerve pallor. 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 an Impact on Hearing From ATYR1940 Treatment
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.
Secondary Outcome Measures
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Titers through Week 12 are summarized.
Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL)
Participants with Jo-1 Ab levels ≥1.5 units/milliliter (U/mL) were to be discontinued from dosing of the study drug.
Number of Participants With Infusion-Related Reactions
Infusion-related reactions included fever, chills, rigors, myalgia, facial erythema, systemic erythema, pallor, facial swelling, chest tightness, difficulty breathing, wheezing, stridor, tachypnea, bronchospasm, cough, tachycardia, significant pulse rate increase from baseline without obvious cause, bradycardia, significant pulse rate decrease from baseline, pre-syncope or syncope, hypotension, orthostatic hypotension, blood pressure swings (including hypertension), skin rash, urticaria, angioedema, pruritus, difficulty speaking, hoarse voice, raspy voice, excessive salivation, difficulty swallowing, nausea, vomiting, cramps, diarrhea; swelling of the throat, tongue, mouth, or lip, and development of a headache especially moderate or greater after start of infusion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
MMT was graded on a scale from 0 (no movement) to 10 (normal movement). Each side of the body and the position in which each muscle was tested were recorded for each participant. The total MMT score were calculated by averaging a converted-MMT scores across all tested muscle groups. Decreased motor function was indicated by decreased individual muscle or composite MMT score.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02603562
Brief Title
Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy
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 Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
March 30, 2016 (Actual)
Primary Completion Date
December 12, 2016 (Actual)
Study Completion Date
December 12, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
aTyr Pharma, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the safety and biological activity of ATYR1940 in participants with early onset FSHD.
Detailed Description
A Phase 1b/2 open-label, intraparticipant dose-escalation study aiming to evaluate the safety, tolerability, immunogenicity, biological and pharmacodynamic activity of intravenous ATYR1940, administered once weekly for 12 weeks, in early onset FSHD participants with signs or symptoms prior to 10 years of age.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facioscapulohumeral Muscular Dystrophy (FSHD)
Keywords
FSHD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ATYR1940
Arm Type
Experimental
Arm Description
Participants received ATYR1940 intravenous (IV) infusion at doses of 0.3, 1.0, and 3.0 milligrams/kilograms (mg/kg) once weekly using intraparticipant dose escalation for 12 weeks.
Intervention Type
Biological
Intervention Name(s)
ATYR1940
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. AEs were 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. SAEs were 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, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, 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 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]); and 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 an Ocular Abnormality Leading to a TEAE
Description
Ocular parameters included vitreous, retina, macula, choroid, optic nerve, and optic nerve pallor. 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 an Impact on Hearing From ATYR1940 Treatment
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)
Secondary Outcome Measure Information:
Title
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Description
Titers through Week 12 are summarized.
Time Frame
Baseline up to Week 12
Title
Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL)
Description
Participants with Jo-1 Ab levels ≥1.5 units/milliliter (U/mL) were to be discontinued from dosing of the study drug.
Time Frame
Baseline up to Week 12
Title
Number of Participants With Infusion-Related Reactions
Description
Infusion-related reactions included fever, chills, rigors, myalgia, facial erythema, systemic erythema, pallor, facial swelling, chest tightness, difficulty breathing, wheezing, stridor, tachypnea, bronchospasm, cough, tachycardia, significant pulse rate increase from baseline without obvious cause, bradycardia, significant pulse rate decrease from baseline, pre-syncope or syncope, hypotension, orthostatic hypotension, blood pressure swings (including hypertension), skin rash, urticaria, angioedema, pruritus, difficulty speaking, hoarse voice, raspy voice, excessive salivation, difficulty swallowing, nausea, vomiting, cramps, diarrhea; swelling of the throat, tongue, mouth, or lip, and development of a headache especially moderate or greater after start of infusion. 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
Baseline up to Week 12
Title
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
Description
MMT was graded on a scale from 0 (no movement) to 10 (normal movement). Each side of the body and the position in which each muscle was tested were recorded for each participant. The total MMT score were calculated by averaging a converted-MMT scores across all tested muscle groups. Decreased motor function was indicated by decreased individual muscle or composite MMT score.
Time Frame
Baseline, Week 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Established, genetically confirmed diagnosis of FSHD.
Onset of FSHD signs or symptoms prior to 10 years of age, as documented in the participant's medical record or based on participant or family report.
Provide written informed consent or assent
In the Investigator's opinion, participant is willing and able to complete all study procedures and comply with the weekly study visit schedule.
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 or activity 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 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
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
OSU Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
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
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
City
Milano
ZIP/Postal Code
20133
Country
Italy
12. IPD Sharing Statement
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Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy
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