Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)

An Open-Label, Intrapatient Dose Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients With Limb Girdle and Facioscapulohumeral Muscular Dystrophies

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02579239

Acronym

FSHD

Enrollment

Registered

2015-10-19

Start date

2015-11-30

Completion date

2016-10-05

Last updated

2023-10-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Facioscapulohumeral Muscular Dystrophy, Limb-Girdle Muscular Dystrophies

Keywords

LGMD2B, FSHD

Brief summary

The purpose of this study is to assess the safety and biological activity of ATYR1940 in participants with LGMD2B and FSHD.

Interventions

BIOLOGICALATYR1940

Concentrate for solution for infusion

BIOLOGICALPlacebo

Concentrate for solution for infusion

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Provided informed consent. * Investigator's opinion, participant is willing and able to complete all study procedures and comply with the study visit schedule. Participant with LGMD2B: * Established, genetically confirmed diagnosis of LGMD2B. * Either the presence of a short tau inversion recovery (STIR) positive muscle on lower extremity skeletal muscle magnetic resonance imaging (MRI), or, if no STIR positive muscles, meets muscle biomarker criteria. Participant with FSHD: * Established, genetically confirmed diagnosis of FSHD. * The presence of a STIR positive muscle on lower extremity skeletal muscle MRI.

Exclusion criteria

* Currently receiving treatment with an immunomodulatory agent, including targeted biological therapies within the 3 months before baseline; corticosteroids within 3 months before baseline; or high-dose non-steroidal anti-inflammatory agents within 2 weeks before baseline. * Currently receiving curcumin or albuterol; use of a product that putatively enhances muscle growth on a chronic basis within 30 days before baseline; statin treatment initiation or significant adjustment to statin regimen within 3 months before baseline (stable, chronic statin use is permissible). * Use of an investigational product or device within 30 days before baseline. * Evidence of an alternative diagnosis other than LGMD2B or FSHD or a coexisting myopathy or dystrophy, based on prior muscle biopsy or other available investigations. * History of severe restrictive or obstructive lung disease or evidence for interstitial lung disease on screening chest radiograph. * History of anti-synthetase syndrome, prior Jo-1 Ab-positivity, or a positive or equivocally positive Jo-1 Ab test result during screening. * Chronic infection, such as hepatitis B, hepatitis C, or human immunodeficiency virus or a history of tuberculosis. * Vaccination within 8 weeks before baseline or vaccination is planned during study participation. * Symptomatic cardiomyopathy or severe cardiac arrhythmia that may in the Investigator's opinion, limit the participant's ability to complete the study protocol. * Muscle biopsy within 30 days before baseline.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Up to End of Study (up to Week 25)	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 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. An SAE was 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, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.
Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE	Up to End of Study (up to Week 25)	ECG parameters that were evaluated included heart rate, PR, and 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.
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE	Up to End of Study (up to Week 25)	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.
Number of Participants With a Clinical Laboratory Abnormality Leading to an AE	Up to End of Study (up to Week 25)	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 \[(nonfasting\]); 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.
Number of Participants With Vital Sign Abnormality Resulting in a TEAE	Up to End of Study (Up to Week 25)	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.

Secondary

Measure	Time frame	Description
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14	Baseline, Week 14	MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.

Countries

Denmark, France, United States

Participant flow

Participants by arm

Arm	Count
Group A - FSHD Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	4
Group B - LGMD2B and FSHD Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	14
Total	18

Baseline characteristics

Characteristic	Group A - FSHD	Group B - LGMD2B and FSHD	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	4 Participants	14 Participants	18 Participants
Age, Continuous	45.0 years STANDARD_DEVIATION 4.97	36.3 years STANDARD_DEVIATION 11.15	38.2 years STANDARD_DEVIATION 10.65
Sex: Female, Male Female	1 Participants	7 Participants	8 Participants
Sex: Female, Male Male	3 Participants	7 Participants	10 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	4 / 4	14 / 14
serious Total, serious adverse events	0 / 4	0 / 14

Outcome results

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 \[(nonfasting\]); 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 Week 25)