A Phase 1/2 interventional study of ATYR1940 in Facioscapulohumeral Muscular Dystrophy and Limb Girdle Muscular Dystrophy, sponsored by aTyr Pharma, Inc.. Completed at 5 sites in 3 countries. Open to participants aged 16 Years to 25 Years. Per ClinicalTrials.gov, last updated 2023-12-22.
Sponsored by aTyr Pharma, Inc. · Phase 1/2, Interventional, and Treatment
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.
548 studies on the registry are indexed under Muscular Dystrophies; 89 are open to participants now.
This study's enrollment of 8 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 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).
Drug: ATYR1940
Concentrate for solution for infusion
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.
Time frame: Up to End of Study (up to approximately Week 39)
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Summarized titers are reported below.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 12
Change From Baseline in Creatinine Kinase at Week 12
Time frame: Baseline, Week 12
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.
| Milestone | ATYR1940 |
|---|---|
| Started | 8 |
| Received at least one dose of study drug | 8 |
| Completed | 8 |
| Not completed | 0 |
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.
| Participants | ATYR1940 |
|---|---|
| TEAEs | 7 |
| SAEs | 0 |
Summarized titers are reported below.
| Participants | ATYR1940 |
|---|---|
| Number of Participants With Positive Anti-Drug Antibodies (ADA) | 3 |
Participants with Jo-1 Ab levels ≥1.5 U/mL were to be discontinued from dosing of the study drug.
| Participants | ATYR1940 |
|---|---|
| Number of Participants With a Jo-1 Antibody (Ab) Test Result ≥1.5 Units/Milliliter (U/mL) | 2 |
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.
| Participants | ATYR1940 |
|---|---|
| Number of Participants With a Clinical Laboratory Abnormality Leading to an AE | 1 |
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.
| Participants | ATYR1940 |
|---|---|
| Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE | 0 |
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.
| Participants | ATYR1940 |
|---|---|
| Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE | 2 |
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 | ATYR1940 |
|---|---|
| Number of Participants With Vital Sign Abnormality Resulting in a TEAE | 0 |
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.
| score on a scale | ATYR1940 |
|---|---|
| Baseline | 229.1 ± 82.56 |
| Change at Week 12 | 4.3 ± 13.50 |
| Units/liter | ATYR1940 |
|---|---|
| Change From Baseline in Creatinine Kinase at Week 12 | -82.3 ± 164.98 |
Collected over Baseline up to approximately Week 39. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ATYR1940 | 0/8 (0%) | 0/8 (0%) | 7/8 (87.5%) |
| Event | ATYR1940 |
|---|---|
| Ovarian cystReproductive system and breast disorders | 1/1 |
| NauseaGastrointestinal disorders | 4/8 |
| FallInjury, poisoning and procedural complications | 4/8 |
| Back painMusculoskeletal and connective tissue disorders | 3/8 |
| MyalgiaMusculoskeletal and connective tissue disorders | 3/8 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 3/8 |
| FatigueGeneral disorders | 2/8 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 2/8 |
| HeadacheNervous system disorders | 2/8 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/8 |
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.
| Age, Continuous(years) | ATYR1940 |
|---|---|
| Mean | 30.0 ± 15.94 |
| Sex: Female, Male(Participants) | ATYR1940 |
|---|---|
| Female | 1 |
| Male | 7 |
| Ethnicity (NIH/OMB)(Participants) | ATYR1940 |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 7 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | ATYR1940 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 8 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is completed, as verified in Dec 2023. 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.