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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003346-27 | EudraCT Number |
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The purpose of this study is to assess the safety and biological activity of ATYR1940 in participants with early onset FSHD.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATYR1940 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATYR1940 | Biological | Concentrate for solution for infusion |
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| 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 Week 25) |
| 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. | Up to End of Study (Up to Week 25) |
| Number of Participants With an Ocular Abnormality Leading to a TEAE |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | Titers through Week 12 are summarized. | Baseline up to Week 12 |
| Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305 | United States | ||
| University of Iowa Children's Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | ATYR1940 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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.
| Up to End of Study (Up to Week 25) |
| Number of Participants With an Impact on Hearing From ATYR1940 Treatment | Up to End of Study (Up to Week 25) |
| 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 Week 25) |
Participants with Jo-1 Ab levels ≥1.5 units/milliliter (U/mL) were to be discontinued from dosing of the study drug.
| Baseline up to Week 12 |
| 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. | Baseline up to Week 12 |
| 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. | Baseline, Week 14 |
| Iowa City |
| Iowa |
| 52242 |
| United States |
| OSU Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET) | Marseille | 13385 | France |
| Institut de Myologie | Paris | 75651 | France |
| Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta | Milan | 20133 | Italy |
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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| ID | Title | Description |
|---|---|---|
| BG000 | ATYR1940 | Participants received ATYR1940 IV infusion at doses of 0.3, 1.0, and 3.0 mg/kg once weekly using intraparticipant dose escalation for 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| 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 analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Up to End of Study (up to Week 25) |
|
|
| |||||||||||||||||||||||||||||||||
| 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 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. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Up to End of Study (Up to Week 25) |
| |||||||||||||||||||||||||||||||||||
| Primary | 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. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Up to End of Study (Up to Week 25) |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With an Impact on Hearing From ATYR1940 Treatment | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Up to End of Study (Up to Week 25) |
|
| |||||||||||||||||||||||||||||||||||
| 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 analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Up to End of Study (up to Week 25) |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Positive Anti-Drug Antibodies (ADA) | Titers through Week 12 are summarized. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. | Posted | Mean | Full Range | percent change | Baseline, Week 14 |
|
|
Up to End of Study (Up to Week 25)
Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. 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 IV infusion at doses of 0.3, 1.0, and 3.0 mg/kg once weekly using intraparticipant dose escalation for 12 weeks. | 0 | 8 | 8 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Paraesthesia | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (18.1) | Non-systematic Assessment |
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| Muscular weakness | 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 |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Ageusia | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Burning sensation | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA (18.1) | Non-systematic Assessment |
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| Conjunctivitis bacterial | Infections and infestations | MedDRA (18.1) | Non-systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA (18.1) | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (18.1) | Non-systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (18.1) | Non-systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA (18.1) | Non-systematic Assessment |
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| Post procedural contusion | Injury, poisoning and procedural complications | MedDRA (18.1) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Chills | General disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Pain | General disorders | 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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| Troponin increased | Investigations | MedDRA (18.1) | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Non-systematic Assessment |
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| Dermatitis contact | 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 |
| ID | Term |
|---|---|
| D020391 | Muscular Dystrophy, Facioscapulohumeral |
| 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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