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ATYR1940-C-006 is a multi-national, multicenter study being conducted at centers in the United States (US) and Europe who participated in Study ATYR1940-C-003 (Stage 1 only) or Study ATYR1940-C-004 (that is, the parent studies).
Study ATYR1940-C-006 is a multi-national, multi-center, open-label extension study designed to evaluate the long-term safety, effects on muscle, and pharmacodynamics of ATYR1940 in participants with Limb-girdle muscular dystrophy (LGMD) or FSHD previously treated in the Study ATYR1940-C-003 (Stage 1 only) or Study ATYR1940-C-004 that is, the parent studies). This study will be conducted at the same study centers at which participants were enrolled in the parent studies.
Participants who completed the treatment period in the parent study and, in the Investigator's opinion, demonstrated acceptable tolerability of ATYR1940, are considered by the Investigator to be compliant with ATYR1940 and the study procedures, and do not meet any criterion for ATYR1940 discontinuation are eligible for participation in the current study, contingent upon Investigator and participant agreement to continue ATYR1940 treatment.
For the first 12 weeks in this extension study, participants will receive ATYR1940 at the highest tolerated dose received in the parent study; no dose adjustments are allowed during this 12-week period. After 12 weeks, if the participant is demonstrating good tolerability, the ATYR1940 dose may be increased on a participant-specific basis at the Investigator's discretion, in consultation with the Sponsor and Medical Monitor. ATYR1940 dose increases to >3.0 mg/kg are not permissible.
All participants will receive ATYR1940 on a weekly basis in this study, regardless of the frequency of dosing in the parent study. ATYR1940 will be administered via intravenous (IV) infusion over 90 minutes. If medically indicated, the infusion duration and volume may be adjusted at the Investigator's discretion in consultation with the Medical Monitor and Sponsor.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATYR1940 | Experimental | Participants will receive ATYR1940 up to 3.0 milligrams per kilograms (mg/kg) intravenous (IV) infusion once weekly until approval of ATYR1940, discontinuation of its development, the study was closed by the Sponsor, or a criterion for study drug discontinuation (up to 34 weeks). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATYR1940 | Drug | Concentrate for solution for infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to End of Study (up to approximately Week 39) |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | Summarized titers are reported below. | Up to End of Study (up to approximately Week 39) |
| 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 U/mL were to be discontinued from dosing of the study drug. | Up to End of Study (up to approximately Week 39) |
| 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 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Creatinine Kinase at Week 12 | Baseline, Week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Irvine, ALS and Neuromuscular Center | Irvine | California | 92697 | United States | ||
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When a participant transferred from the parent study to this extension study, the duration between the last ATYR1940 dose in the parent study and first ATYR1940 dose in this extension study was to be 1 week; however, a maximum duration of 3 weeks was permissible.
Participants who participated in and completed the treatment period and were considered to be compliant with the study drug by the Investigator in the parent studies (ATYR1940-C-003 [NCT02603562] or ATYR1940-C-004 [NCT02579239]) were eligible for participation in this study. Note that only data for this study are reported in this Results Record. Data for the parent studies (ATYR1940-C-003 [NCT02603562] and ATYR1940-C-004 [NCT02579239]) are reported in the respective Results Records.
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| ID | Title | Description |
|---|---|---|
| FG000 | ATYR1940 | Participants received ATYR1940 up to 3.0 milligrams per kilograms (mg/kg) intravenous (IV) infusion once weekly until approval of ATYR1940, discontinuation of its development, the study was closed by the Sponsor, or a criterion for study drug discontinuation was met (up to a maximum of 34 weeks). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 22, 2016 | Oct 3, 2023 |
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| Up to End of Study (up to approximately Week 39) |
| 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. | Up to End of Study (up to approximately Week 39) |
| Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE | ECG parameters that were evaluated included heart rate and PR, 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. | Up to End of Study (up to approximately Week 39) |
| 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. | Up to End of Study (up to approximately Week 39) |
| Change From Baseline in Manual Muscle Testing (MMT) Score at Week 12 | MMT (muscle strength) will be graded using a modified Medical Research Council scale. Scores were converted to 13-point scale (range from 0 [on contraction palpable] to 12 [normal strength]). An overall total score was calculated by summing all scores for a total possible score of 336. Decreased muscle strength was indicated by a decreased score. An overall total score was calculated as long as 24 of the 28 individual scores were non-missing. | Baseline, Week 12 |
| Stanford University |
| Stanford |
| California |
| 94305 |
| United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Rigshospitalet, University of Copenhagen | Copenhagen | Denmark |
| Foundation IRCCS Neurological Institute Carlo | Milan | 20133 | Italy |
| Received at Least One Dose of Study Drug |
|
| COMPLETED |
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| NOT COMPLETED |
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Cumulative Safety population included all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies, but with cumulative data from both the parent studies and the current study.
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| ID | Title | Description |
|---|---|---|
| BG000 | ATYR1940 | Participants received ATYR1940 up to 3.0 mg/kg IV infusion once weekly until approval of ATYR1940, discontinuation of its development, the study was closed by the Sponsor, or a criterion for study drug discontinuation was met (up to a maximum of 34 weeks). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 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. | Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
|
| |||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Positive Anti-Drug Antibodies (ADA) | Summarized titers are reported below. | Cumulative Safety population included all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies, but with cumulative data from both the parent studies and the current study. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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 U/mL were to be discontinued from dosing of the study drug. | Cumulative Safety population included all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies, but with cumulative data from both the parent studies and the current study. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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 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. | Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
| |||||||||||||||||||||||||||||||||||
| Primary | 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. | Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE | ECG parameters that were evaluated included heart rate and PR, 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. | Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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. | Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. | Posted | Count of Participants | Participants | Up to End of Study (up to approximately Week 39) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Manual Muscle Testing (MMT) Score at Week 12 | MMT (muscle strength) will be graded using a modified Medical Research Council scale. Scores were converted to 13-point scale (range from 0 [on contraction palpable] to 12 [normal strength]). An overall total score was calculated by summing all scores for a total possible score of 336. Decreased muscle strength was indicated by a decreased score. An overall total score was calculated as long as 24 of the 28 individual scores were non-missing. | Cumulative Safety population included all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies, but with cumulative data from both the parent studies and the current study. Here, 'Number of Participants analyzed' signifies those who were evaluable for this outcome measure and number analyzed signifies those who were evaluable at specified time points only. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
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| Secondary | Change From Baseline in Creatinine Kinase at Week 12 | Cumulative Safety population included all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies, but with cumulative data from both the parent studies and the current study. Here, 'Number of Participants analyzed' signifies those who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Units/liter | Baseline, Week 12 |
|
|
Baseline up to approximately Week 39
Safety population was defined as all participants who received at least 1 full or partial dose of ATYR1940 in the current study (Study ATYR1940-C-006) and had a post-infusion safety observation since enrollment in parent studies. Mortality, Serious Adverse Event, and Other Adverse Event data were prespecified to be collected as a single Arm/Group for any participant who received at least 1 dose of the study drug, regardless of their dose level.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ATYR1940 | Participants received ATYR1940 up to 3.0 mg/kg IV infusion once weekly until approval of ATYR1940, discontinuation of its development, the study was closed by the Sponsor, or a criterion for study drug discontinuation was met (up to a maximum of 34 weeks). | 0 | 8 | 0 | 8 | 7 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Cyst | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Infusion site pain | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Back injury | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Bone contusion | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
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| Laryngitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
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| Blood bicarbonate decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
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| ECG signs of ventricular hypertrophy | Investigations | MedDRA 18.1 | Non-systematic Assessment |
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| Electrocardiogram P wave biphasic | Investigations | MedDRA 18.1 | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Burning sensation | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Atrioventricular block first degree | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Right atrial dilatation | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Ovarian cyst | Reproductive system and breast disorders | MedDRA 18.1 | Non-systematic Assessment | This AE is gender specific. |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | aTyr Pharma | 858 731 8389 | clinicaltrials@atyrpharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 19, 2017 | Oct 3, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D020391 | Muscular Dystrophy, Facioscapulohumeral |
| D049288 | Muscular Dystrophies, Limb-Girdle |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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