A Phase 1/2 interventional study of Placebo and ATYR1940 in Facioscapulohumeral Muscular Dystrophy (FSHD), sponsored by aTyr Pharma, Inc.. Completed at 5 sites in 4 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-08-11.
Sponsored by aTyr Pharma, Inc. · Phase 1/2, Interventional, and Treatment
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
Study ATYR1940-C-002 is a multi-national, multi-center, double-blind, randomized, placebo-controlled, ascending dose study designed to evaluate the safety, tolerability, PK, immunogenicity, and pharmacodynamic effects of ATYR1940 in participants with FSHD. Up to 44 participants are planned to be enrolled at multiple study centers in the United States and Europe; the actual number of participants enrolled will depend on the number of cohorts initiated.
Participants will be screened for study eligibility during the Screening period within 3 weeks before Baseline (that is, Day 1, the first day of Study Drug administration). Eligible participants, based on Screening assessments, will be randomly assigned to treatment with ATYR1940 or placebo. Participants who are randomized will be considered enrolled in the study.
548 studies on the registry are indexed under Muscular Dystrophies; 89 are open to participants now.
This study's enrollment of 20 is below the median of 24 across 344 interventional studies indexed under Muscular Dystrophies.
Browse Muscular Dystrophies studies →aTyr Pharma, Inc. is the lead sponsor of 9 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will receive ATYR1940 0.3 milligrams/kilograms (mg/kg) intravenous (IV) infusion once weekly for 4 weeks.
Biological: ATYR1940
Participants will receive ATYR1940 1.0 mg/kg IV infusion once weekly for 4 weeks.
Biological: ATYR1940
Participants will receive ATYR1940 3.0 mg/kg IV infusion once weekly for 12 weeks.
Biological: ATYR1940
Participants will receive placebo matched to ATYR1940 IV infusion once weekly for 4 weeks in Cohorts 1 and 2 and for 12 weeks in Cohort 3.
Biological: Placebo
Concentrate for solution for infusion
Concentrate for solution for infusion
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with study drug. Worsening of a pre-existing medical condition, (that is, diabetes, migraine headaches, gout) 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. Classification of AEs was to be done by the Investigator according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to End of Study (up to Week 25)
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Titers through Week 14 are summarized. For Cohorts 1 and 2, samples that screened positive but did not confirm on confirmatory assay were not titered.
Time frame: Baseline up to Week 14
Number of Participants With a Positive or Equivocal Jo-1 Antibody (Ab) Test Result
Criterion for a positive Jo-1 Ab test result: \>10.0 units/milliliter (U/mL), a cut-point associated with anti-synthetase syndrome. Criterion for an equivocal Jo-1 Ab test result: 7.0 to 10.0 U/mL. Participants were required to have a negative Jo-1 Ab test result (defined as \<7 U/mL) for inclusion in the study as well as to continue dosing with study drug during the study.
Time frame: Baseline up to Week 14
Number of Participants With a Clinically Significant Laboratory Abnormality
Laboratory parameters included hematology (hematocrit, hemoglobin, platelet count, red blood cell count, white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, basophils); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), alkaline phosphatase, sodium, total protein, bicarbonate, potassium, calcium, chloride, magnesium, inorganic phosphate, creatine phosphokinase \[will be fractionated if elevated\], lactic dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, cholesterol \[non-fasting\]); Urinalysis (Color, pH, specific gravity, protein, glucose, ketones, blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious AEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Baseline up to Week 14
Number of Participants With a Physical Examination Abnormality
Body systems that were evaluated during the physical examination included general appearance, head, eyes, ears, nose, throat (HEENT), cardiovascular system, respiratory system, chest (breasts), gastrointestinal system (abdomen), lymphatic system, musculoskeletal system, skin, psychiatric, and neurologic. Neurologic examination included assessment of mental status, memory, cranial nerves, motor function, and reflexes, and sensory testing. The body systems with at least 1 physical abnormality is presented. One participant could be represented in more than 1 body system category. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to End of Study (up to Week 25)
Number of Participants With a Vital Sign-Related Event 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.
Time frame: Up to End of Study (Up to Week 25)
Number of Participants With a Pulmonary Function Event Resulting in a TEAE
Pulmonary function testing included measurements of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to End of Study (Up to Week 25)
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 6 and 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.
Time frame: Baseline, Week 6 and Week 14
Change From Baseline in Individualized Neuromuscular Quality of Life (INQoL) - Overall QoL at Week 6 and Week 14
The INQoL is a validated muscle disease-specific measure of quality of life. The self-administered questionnaire consisted of 45 questions with 4 domains measuring the impact of common muscle disease symptoms (weakness, locking \[or myotonia\], pain, and fatigue); 5 domains measuring the influence of the muscle disease on particular areas of life (activities, independence, relationships, emotions, and body image); and the last domain focused on the positive and negative effects of treatment and was divided into 2 scores. All responses were given in a 7-point Likert scale, with improved QoL indicated by decreased scores. Overall QoL score was calculated from preselected 5 domains (activities, independence, relationships, emotions, and body image) by adding the scores from each domain. In summary, INQoL yielded 11 scores and 1 QoL score. The Overall scoring used a scale of 0-100, with improved QoL indicated by decreased scores.
Time frame: Baseline, Week 6 and Week 14
Maximum Observed Plasma Concentration (Cmax) of ATYR1940
Time frame: Cohort 1: Predose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after the start of infusion at Weeks 2 and 5; Cohorts 2 and 3: Predose, 0.5, 1.0, 2.0, 4.0, and 6.0 hours after the start of infusion at Weeks 2, 5, and 13 (Cohort 3 only)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATYR1940
Time frame: Cohort 1: Predose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after the start of infusion at Weeks 2 and 5; Cohorts 2 and 3: Predose, 0.5, 1.0, 2.0, 4.0, and 6.0 hours after the start of infusion at Weeks 2, 5, and 13 (Cohort 3 only)
Area Under the Plasma Concentration Time Curve From Time 0 to Time t (AUC 0-t) of ATYR1940
Time frame: Cohort 1: Predose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after the start of infusion at Weeks 2 and 5; Cohorts 2 and 3: Predose, 0.5, 1.0, 2.0, 4.0, and 6.0 hours after the start of infusion at Weeks 2, 5, and 13 (Cohort 3 only)
Average of Half-life (T1/2) of ATYR1940
Time frame: Cohort 1: Predose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after the start of infusion at Weeks 2 and 5; Cohorts 2 and 3: Predose, 0.5, 1.0, 2.0, 4.0, and 6.0 hours after the start of infusion at Weeks 2, 5, and 13 (Cohort 3 only)
| Milestone | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Started | 3 | 6 | 6 | 5 |
| Received at least one dose of study drug | 3 | 6 | 6 | 5 |
| Completed | 3 | 6 | 3 | 4 |
| Not completed | 0 | 0 | 3 | 1 |
| Withdrew: Administrative | 0 | 0 | 3 | 1 |
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with study drug. Worsening of a pre-existing medical condition, (that is, diabetes, migraine headaches, gout) 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. Classification of AEs was to be done by the Investigator according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 | 6 | 6 | 5 |
Titers through Week 14 are summarized. For Cohorts 1 and 2, samples that screened positive but did not confirm on confirmatory assay were not titered.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | 2 | 1 | 3 | 0 |
Criterion for a positive Jo-1 Ab test result: \>10.0 units/milliliter (U/mL), a cut-point associated with anti-synthetase syndrome. Criterion for an equivocal Jo-1 Ab test result: 7.0 to 10.0 U/mL. Participants were required to have a negative Jo-1 Ab test result (defined as \<7 U/mL) for inclusion in the study as well as to continue dosing with study drug during the study.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With a Positive or Equivocal Jo-1 Antibody (Ab) Test Result | 0 | 0 | 0 | 0 |
Laboratory parameters included hematology (hematocrit, hemoglobin, platelet count, red blood cell count, white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, basophils); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), alkaline phosphatase, sodium, total protein, bicarbonate, potassium, calcium, chloride, magnesium, inorganic phosphate, creatine phosphokinase \[will be fractionated if elevated\], lactic dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, cholesterol \[non-fasting\]); Urinalysis (Color, pH, specific gravity, protein, glucose, ketones, blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious AEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With a Clinically Significant Laboratory Abnormality | 0 | 2 | 0 | 0 |
Body systems that were evaluated during the physical examination included general appearance, head, eyes, ears, nose, throat (HEENT), cardiovascular system, respiratory system, chest (breasts), gastrointestinal system (abdomen), lymphatic system, musculoskeletal system, skin, psychiatric, and neurologic. Neurologic examination included assessment of mental status, memory, cranial nerves, motor function, and reflexes, and sensory testing. The body systems with at least 1 physical abnormality is presented. One participant could be represented in more than 1 body system category. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| General appearance | 0 | 1 | 0 | 0 |
| HEENT | 0 | 1 | 0 | 0 |
| Lymphatic system | 0 | 0 | 0 | 1 |
| Musculoskeletal system | 0 | 1 | 0 | 1 |
| Respiratory system | 0 | 1 | 0 | 0 |
| Skin | 0 | 1 | 1 | 0 |
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.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With a Vital Sign-Related Event Resulting in a TEAE | 0 | 0 | 1 | 0 |
Pulmonary function testing included measurements of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Participants | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Number of Participants With a Pulmonary Function Event Resulting in a TEAE | 0 | 1 | 0 | 0 |
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.
| percent change | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Change at Week 6 | 2.83 (1.0 to 4.4) | 3.07 (0.7 to 5.6) | -0.85 (-5.1 to 5.5) | 1.34 (-3.3 to 7.8) |
| Change at Week 14 | — | — | 0.70 (-5.9 to 9.2) | -1.40 (-1.5 to -1.3) |
The INQoL is a validated muscle disease-specific measure of quality of life. The self-administered questionnaire consisted of 45 questions with 4 domains measuring the impact of common muscle disease symptoms (weakness, locking \[or myotonia\], pain, and fatigue); 5 domains measuring the influence of the muscle disease on particular areas of life (activities, independence, relationships, emotions, and body image); and the last domain focused on the positive and negative effects of treatment and was divided into 2 scores. All responses were given in a 7-point Likert scale, with improved QoL indicated by decreased scores. Overall QoL score was calculated from preselected 5 domains (activities, independence, relationships, emotions, and body image) by adding the scores from each domain. In summary, INQoL yielded 11 scores and 1 QoL score. The Overall scoring used a scale of 0-100, with improved QoL indicated by decreased scores.
| score on a scale | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Baseline | 54.37 (36.8 to 68.4) | 72.80 (63.2 to 84.2) | 69.30 (52.6 to 78.9) | 53.68 (36.8 to 73.7) |
| Change at Week 6 | 2.77 (-5.0 to 6.7) | -2.98 (-16.1 to 8.4) | -3.78 (-16.6 to 16.7) | 4.12 (-8.3 to 22.2) |
| Change at Week 14 | — | — | -9.90 (-19.4 to 5.0) | 15.55 (3.9 to 27.2) |
| nanogram/milliliter | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg |
|---|---|---|---|
| Week 2 | 1360 ± 267 | 6800 ± 752 | 21900 ± 6960 |
| Week 5 | 1980 ± 249 | 7490 ± 1040 | 23800 ± 8780 |
| Week 13 | — | — | 26200 ± 14200 |
| hours | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg |
|---|---|---|---|
| Week 2 | 0.417 ± 0.144 | 0.500 ± 0 | 0.500 ± 0 |
| Week 5 | 0.500 ± 0 | 0.500 ± 0 | 0.500 ± 0 |
| Week 13 | — | — | 0.500 ± 0 |
| nanogram*hour/milliliter | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg |
|---|---|---|---|
| Week 2 | 5800 ± 1480 | 24200 ± 1490 | 82200 ± 25500 |
| Week 5 | 8550 ± 1350 | 26500 ± 2650 | 83700 ± 25800 |
| Week 13 | — | — | 84400 ± 36200 |
| hours | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg |
|---|---|---|---|
| Week 2 | 3.91 ± 0.193 | 3.68 ± 0.354 | 4.33 ± 0.772 |
| Week 5 | 4.16 ± 1.04 | 3.91 ± 1.29 | 4.32 ± 0.823 |
| Week 13 | — | — | 5.09 ± 2.64 |
Collected over Up to End of Study (up to Week 25). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: ATYR1940 0.3 mg/kg | — | 0/3 (0%) | 3/3 (100%) |
| Cohort 2: ATYR1940 1.0 mg/kg | — | 0/6 (0%) | 6/6 (100%) |
| Cohort 3: ATYR1940 3.0 mg/kg | — | 1/6 (16.7%) | 6/6 (100%) |
| Placebo | — | 0/5 (0%) | 5/5 (100%) |
| Event | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| Infusion-related ReactionGeneral disorders | 0/3 | 0/6 | 1/6 | 0/5 |
| Event | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo |
|---|---|---|---|---|
| ArthralgiaMusculoskeletal and connective tissue disorders | 2/3 | 0/6 | 1/6 | 0/5 |
| Back PainMusculoskeletal and connective tissue disorders | 1/3 | 3/6 | 0/6 | 1/5 |
| PolymenorrhoeaReproductive system and breast disorders | 0/1 | 0/4 | 1/2 | 0/1 |
| HeadacheNervous system disorders | 0/3 | 1/6 | 2/6 | 2/5 |
| NauseaGastrointestinal disorders | 0/3 | 2/6 | 0/6 | 0/5 |
| FatigueGeneral disorders | 1/3 | 0/6 | 0/6 | 0/5 |
| PharyngitisInfections and infestations | 1/3 | 0/6 | 0/6 | 0/5 |
| MyalgiaMusculoskeletal and connective tissue disorders | 1/3 | 1/6 | 0/6 | 1/5 |
| PresyncopeNervous system disorders | 0/3 | 0/6 | 2/6 | 0/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/3 | 0/6 | 2/6 | 0/5 |
Intent to treat (ITT) analysis set included all participants who were randomized and received at least 1 dose (full or partial) of study drug.
| Age, Continuous(years) | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Mean | 44.3 (25 to 55) | 44.5 (33 to 52) | 45.3 (25 to 72) | 54.0 (39 to 66) | 49.35 (25 to 72) |
| Sex: Female, Male(Participants) | Cohort 1: ATYR1940 0.3 mg/kg | Cohort 2: ATYR1940 1.0 mg/kg | Cohort 3: ATYR1940 3.0 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Female | 1 | 4 | 2 | 1 | 8 |
| Male | 2 | 2 | 4 | 4 | 12 |
Plan to share: No
No publications or documents are linked to this record.
This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
aTyr Pharma, Inc.