Facioscapulohumeral Muscular Dystrophy
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability profile of ATYR1940 in the treatment of adult participants with molecularly defined genetic muscular dystrophies.
Detailed description
The purpose of this study is to assess the safety and tolerability profile of ATYR1940 in the treatment of adult participants with molecularly defined genetic muscular dystrophies, and to additionally explore the pharmacokinetics and biologic activity of ATYR1940 in adult participants with molecularly defined genetic muscular dystrophies. Participants who successfully complete the parent study (NCT02239224) are eligible for enrollment into this long-term extension study.
Interventions
BIOLOGICALATYR1940
Concentrate for solution for infusion
Sponsors
aTyr Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant has an established, genetically-confirmed, diagnosis of facioscapulohumeral dystrophy with clinical findings meeting existing criteria. * Participant is a male or female aged 18 to 65 years, inclusive. * Participants who previously participated in study ATYR1940-C-002 and who meet the entry criteria above for the current study will be eligible for enrollment.
Exclusion criteria
* Participant is currently receiving treatment with an immunomodulatory agent or has a history of such treatment, including targeted biological therapies (for example, etanercept, omalizumab) within the 3 months before Baseline; corticosteroids within 4 weeks before Baseline; or non-steroidal anti-inflammatory agents (NSAIDs) within 2 weeks before Baseline. * Participant has a severe retinopathy. * Participant has a history of obstructive or restrictive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for interstitial lung disease on Screening chest radiograph. * Participant has evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention, other treatment or may not allow safe participation. * Participant has used any investigational product or device (other than a mobility assistance device) within 30 days before Baseline. * If female and of childbearing potential (premenopausal and not surgically sterile), participant has a positive pregnancy test at Screening or is unwilling to use contraception from the time of Screening through the 1-month Follow-up visit. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device. * If male, participant is unwilling to use a condom plus spermicide during sexual intercourse from the time of Screening through the 1-month Follow-up visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to End of Study (up to Week 36) | TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. AEs ware 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 Clinically Significant Physical Examination Abnormality | Up to End of Study (up to Week 36) | Body systems that were evaluated during the physical examination included general appearance, head, eyes, ears, nose, throat, cardiovascular system, respiratory system, gastrointestinal system (abdomen), lymphatic system, musculoskeletal system, skin, psychiatric, and neurologic. Neurologic examination included assessment of mental status, memory, cranial nerves, motor function, reflexes, and sensory testing. 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 Vital Sign-Related Event Resulting in a TEAE | Up to End of Study (up to Week 36) | The vital sign parameters that were evaluated included blood pressure, pulse and respiration rates, and body temperature. Vital signs abnormalities that were considered by the Investigator to be clinically significant were reported as AEs if the finding represented a change from baseline. 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 | Up to End of Study (up to Week 36) | Pulmonary evaluations included pulmonary function tests. 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 Resulting in an AE | Up to End of Study (Up to Week 36) | 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, 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. |
Countries
Italy, Netherlands, United States
Participant flow
Pre-assignment details
Participants who participated in Cohort 2 or 3, completed the double-blind treatment period and were considered to be compliant with the study drug by the Investigator in the Study ATYR1940-C-002 (NCT02239224) were eligible for participation in this study.
Participants by arm
| Arm | Count |
|---|---|
| ATYR1940 Participants received ATYR1940 3.0 mg/kg IV infusion once weekly for 24 weeks. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | ATYR1940 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 53.2 years |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Number of Participants With a Clinical Laboratory Abnormality Resulting in 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, 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 36)
Population: ITT analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATYR1940 | Number of Participants With a Clinical Laboratory Abnormality Resulting in an AE | 3 Participants |
Primary
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
Pulmonary evaluations included pulmonary function tests. 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 36)
Population: ITT analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATYR1940 | Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE | 0 Participants |
Primary
Number of Participants With a Vital Sign-Related Event Resulting in a TEAE
The vital sign parameters that were evaluated included blood pressure, pulse and respiration rates, and body temperature. Vital signs abnormalities that were considered by the Investigator to be clinically significant were reported as AEs if the finding represented a change from baseline. 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 36)
Population: ITT analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATYR1940 | Number of Participants With a Vital Sign-Related Event Resulting in a TEAE | 0 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Abnormality
Body systems that were evaluated during the physical examination included general appearance, head, eyes, ears, nose, throat, cardiovascular system, respiratory system, gastrointestinal system (abdomen), lymphatic system, musculoskeletal system, skin, psychiatric, and neurologic. Neurologic examination included assessment of mental status, memory, cranial nerves, motor function, reflexes, and sensory testing. 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 36)
Population: ITT analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATYR1940 | Number of Participants With Clinically Significant Physical Examination Abnormality | 4 Participants |
Primary
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 ware 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 36)
Population: ITT analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATYR1940 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 9 Participants |
| ATYR1940 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |