Trial Outcomes & Findings for Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy (NCT NCT02603562)
NCT ID: NCT02603562
Last Updated: 2023-10-19
Results Overview
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.
COMPLETED
PHASE1/PHASE2
8 participants
Up to End of Study (up to Week 25)
2023-10-19
Participant Flow
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
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8
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Overall Study
Received at Least 1 Dose of Study Drug
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8
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Overall Study
COMPLETED
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7
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Overall Study
NOT COMPLETED
|
1
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Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Lost to Follow-up
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1
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Baseline Characteristics
Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy
Baseline characteristics by cohort
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Age, Categorical
<=18 years
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3 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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5 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
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17.9 years
n=5 Participants
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Sex: Female, Male
Female
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3 Participants
n=5 Participants
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Sex: Female, Male
Male
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5 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Up to End of Study (up to Week 25)Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
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8 Participants
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
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0 Participants
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PRIMARY outcome
Timeframe: Up to End of Study (Up to Week 25)Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With a Clinical Laboratory Abnormality Leading to an AE
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1 Participants
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PRIMARY outcome
Timeframe: Up to End of Study (Up to Week 25)Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With an Ocular Abnormality Leading to a TEAE
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0 Participants
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PRIMARY outcome
Timeframe: Up to End of Study (Up to Week 25)Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With an Impact on Hearing From ATYR1940 Treatment
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0 Participants
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PRIMARY outcome
Timeframe: Up to End of Study (up to Week 25)Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
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0 Participants
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SECONDARY outcome
Timeframe: Baseline up to Week 12Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
Titers through Week 12 are summarized.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With Positive Anti-Drug Antibodies (ADA)
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4 Participants
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SECONDARY outcome
Timeframe: Baseline up to Week 12Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
Participants with Jo-1 Ab levels ≥1.5 units/milliliter (U/mL) were to be discontinued from dosing of the study drug.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL)
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0 Participants
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SECONDARY outcome
Timeframe: Baseline up to Week 12Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Number of Participants With Infusion-Related Reactions
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1 Participants
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SECONDARY outcome
Timeframe: Baseline, Week 14Population: Safety analysis set included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.
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.
Outcome measures
| Measure |
ATYR1940
n=8 Participants
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.
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|---|---|
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Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14
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3.8 percent change
Interval -6.0 to 19.0
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Adverse Events
ATYR1940
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ATYR1940
n=8 participants at risk
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.
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|---|---|
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Nervous system disorders
Paraesthesia
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37.5%
3/8 • 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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Nervous system disorders
Headache
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25.0%
2/8 • 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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Gastrointestinal disorders
Nausea
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25.0%
2/8 • 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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Musculoskeletal and connective tissue disorders
Myalgia
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37.5%
3/8 • 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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Infections and infestations
Nasopharyngitis
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25.0%
2/8 • 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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Musculoskeletal and connective tissue disorders
Muscular weakness
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12.5%
1/8 • 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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Musculoskeletal and connective tissue disorders
Musculoskeletal pain
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12.5%
1/8 • 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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Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
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12.5%
1/8 • 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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Musculoskeletal and connective tissue disorders
Pain in extremity
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12.5%
1/8 • 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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Nervous system disorders
Ageusia
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12.5%
1/8 • 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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Nervous system disorders
Burning sensation
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12.5%
1/8 • 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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Nervous system disorders
Dizziness
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12.5%
1/8 • 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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Nervous system disorders
Presyncope
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12.5%
1/8 • 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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Infections and infestations
Bronchitis
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12.5%
1/8 • 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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Infections and infestations
Conjunctivitis bacterial
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12.5%
1/8 • 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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Infections and infestations
Respiratory tract infection
|
12.5%
1/8 • 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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Injury, poisoning and procedural complications
Fall
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12.5%
1/8 • 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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Injury, poisoning and procedural complications
Infusion related reaction
|
12.5%
1/8 • 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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Injury, poisoning and procedural complications
Limb injury
|
12.5%
1/8 • 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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Injury, poisoning and procedural complications
Post procedural contusion
|
12.5%
1/8 • 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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Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • 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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General disorders
Asthenia
|
12.5%
1/8 • 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.
|
|
General disorders
Chills
|
12.5%
1/8 • 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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General disorders
Pain
|
12.5%
1/8 • 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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Investigations
Electrocardiogram P wave biphasic
|
12.5%
1/8 • 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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Investigations
Troponin increased
|
12.5%
1/8 • 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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Metabolism and nutrition disorders
Decreased appetite
|
12.5%
1/8 • 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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Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
12.5%
1/8 • 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.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
12.5%
1/8 • 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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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place