Evaluate Safety and Biological Activity of ATYR1940 in Participants With Early Onset Facioscapulohumeral Muscular Dystrophy (FSHD)

September 26, 2023 updated by: aTyr Pharma, Inc.

An Open-Label, Intrapatient Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients With Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13385
        • Centre d'nvestigation Clinique - Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques (CICCPCET)
      • Paris, France, 75651
        • Institut de Myologie
  • Italy
      • Milano, Italy, 20133
        • Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Children's Hospital
    • Ohio
      • Columbus, Ohio, United States, 43210
        • OSU Wexner Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Established, genetically confirmed diagnosis of FSHD.
  • Onset of FSHD signs or symptoms prior to 10 years of age, as documented in the participant's medical record or based on participant or family report.
  • Provide written informed consent or assent
  • In the Investigator's opinion, participant is willing and able to complete all study procedures and comply with the weekly study visit schedule.

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 or activity on a chronic basis within 4 weeks 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Biological: ATYR1940
Concentrate for solution for infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE
Time Frame: 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.
Up to End of Study (up to Week 25)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: 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. 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
Time Frame: 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]); 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
Time Frame: Up to End of Study (Up to Week 25)
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
Time Frame: Up to End of Study (Up to Week 25)
Up to End of Study (Up to Week 25)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Positive Anti-Drug Antibodies (ADA)
Time Frame: Baseline up to Week 12
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)
Time Frame: Baseline up to Week 12
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
Time Frame: Baseline up to Week 12
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
Time Frame: Baseline, 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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamic Additional Outcome Measure - Changes in FSHD-related inflammatory immune state
Time Frame: 12 weeks
Effects assessed by changes in muscular dystrophy-related inflammatory immune state in peripheral blood
12 weeks
Pharmacodynamic Additional Outcome Measure - Changes from baseline clinical parameters
Time Frame: 12 weeks
Changes from baseline in muscle strength based on manual muscle strength
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
aTyr Pharma, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Kelly Blackburn, aTyr Pharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 30, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 12, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 12, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 13, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 26, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ATYR1940-C-003
  • 2014-003346-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings