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Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATYR1940 in Adult Patients With Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02239224
Recruitment Status : Completed
First Posted : September 12, 2014
Last Update Posted : July 11, 2017
Sponsor:
Information provided by (Responsible Party):
aTyr Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE September 7, 2014
First Posted Date  ICMJE September 12, 2014
Last Update Posted Date July 11, 2017
Actual Study Start Date  ICMJE August 2014
Actual Primary Completion Date December 21, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2014)
  • Safety and tolerability of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Change from Baseline of physical examination
  • Safety and tolerability of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Change from Baseline in vital sign measurements and pulmonary evaluation
  • Safety and tolerability of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Incidences of Adverse Events (AEs), including serious and severe AEs
  • Safety and tolerability of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Change from Baseline in safety laboratory test results
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2014)
  • Pharmacokinetics of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Cmax: Observed maximum serum concentration
  • Pharmacokinetics of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    Tmax: Time to attain maximum serum concentration
  • Pharmacokinetics of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    T 1/2: Elimination half-life
  • Pharmacokinetics of ATYR1940 in adult patients with molecularly defined genetic muscular dystrophies [ Time Frame: Up to 1 month ]
    AUC 0-t: Area under the serum concentration-time curve up to time t
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATYR1940 in Adult Patients With Muscular Dystrophy
Official Title  ICMJE A Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Biological Activity of ATYR1940 in Adult Patients With Molecularly Defined Genetic Muscular Dystrophies
Brief Summary The purpose of this study is to assess the safety and tolerability profile of ATYR1940 in the treatment of adult patients with molecularly defined genetic muscular dystrophies
Detailed Description

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 patients with FSHD. Up to 44 patients are planned to be enrolled at multiple study centers in the U.S. and Europe; the actual number of patients enrolled will depend on the number of cohorts initiated.

Patients will be screened for study eligibility during the Screening period within 3 weeks before Baseline (i.e., Day 1, the first day of Study Drug administration). Eligible patients, based on Screening assessments, will be randomly assigned to treatment with ATYR1940 or placebo. Patients who are randomized are considered to be enrolled in the study.

After enrollment, patients will enter the 1-week single-blind placebo period during which all patients will receive a single 30-minute IV infusion of placebo. Thereafter, patients will enter the double-blind treatment period and will receive 30-minute IV infusions of Study Drug (ATYR1940 or placebo) according to their random treatment assignment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Facioscapulohumeral Muscular Dystrophy (FSHD)
Intervention  ICMJE
  • Biological: Placebo
    Patients will enter the double-blind treatment period and will receive 30-minute IV infusions of Placebo according to their random treatment assignment.
  • Biological: ATYR1940
    Patients will enter the double-blind treatment period and will receive 30-minute IV infusions of ATYR1940 according to their random treatment assignment.
Study Arms  ICMJE
  • Experimental: ATYR1940
    ATYR1940 : IV; 0.3, 1.0, or 3.0 mg/kg; once a week; Up to 12 weeks
    Intervention: Biological: ATYR1940
  • Placebo Comparator: Placebo
    Placebo: IV; 0.3, 1.0, or 3.0 mg/kg; once a week; Up to 12 weeks
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 27, 2017)
20
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2014)
44
Actual Study Completion Date  ICMJE December 21, 2015
Actual Primary Completion Date December 21, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient is a male or female aged 18 to 65 years, inclusive.
  • Patient has an established, genetically-confirmed, diagnosis of facioscapulohumeral dystrophy with clinical findings meeting existing criteria.
  • Patient has provided written informed consent after the nature of the study has been explained and prior to the performance of any research-related procedures.
  • Patient is, in the Investigator's opinion, willing and able to comply with all study procedures.
  • Cohorts ≥2 only: Patient has imaging findings meeting defined criteria for muscle inflammation in at least 1 skeletal muscle

Exclusion Criteria:

  • Patient is currently receiving treatment with an immunomodulatory agent or has a history of such treatment, including targeted biological therapies (e.g., etanercept, omalizumab) within the 3 months before Baseline; corticosteroids within 4 weeks before Baseline; or high-dose non-steroidal anti-inflammatory agents (NSAIDs) within 2 weeks before Baseline.
  • Patient is currently receiving curcumin or albuterol or requires such treatment during study participation.
  • Patient has evidence of an alternative diagnosis other than FSHD, based on prior muscle biopsy or genetic test findings.
  • Patient has a presumptive diagnosis of FSHD, based on clinical assessment, but does not yet have genetic confirmation of the diagnosis.
  • Patient has a severe retinopathy.
  • Patient has a history of obstructive or restrictive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for interstitial lung disease on Screening chest radiograph.
  • Patient has a history of anti-synthetase syndrome, prior Jo-1 antibody (Ab)-positivity, or has a positive or equivocally positive Jo-1 Ab test result during Screening.
  • Patient has acute or clinically relevant Epstein-Barr virus or cytomegalovirus infection or re-activation.
  • Patient has a chronic infection such as hepatitis B virus, hepatitis C virus, or human immunodeficiency virus or a history of tuberculosis.
  • Patient has received a vaccination within 8 weeks before Baseline or vaccination is planned during study participation.
  • Patient has symptomatic cardiomyopathy or severe cardiac arrhythmia that may, in the Investigator's opinion, limit the patient's ability to complete the study protocol.
  • Patient has anemia (as defined for patient's age and gender by local laboratory range).
  • Patient has gamma-glutamyl transferase (GGT) or serum creatinine levels >2 × the upper limit of normal (ULN).
  • Patient has abnormal baseline findings, medical condition(s), or laboratory findings that, in the Investigator's opinion, might jeopardize patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
  • Patient has evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a condition that requires immediate surgical intervention or other treatment or may not allow safe participation.
  • Patient has used any investigational product or device (other than a mobility assistance device) within 30 days before Baseline.
  • Patient has received a product intended to enhance muscle growth within 30 days before Baseline.
  • Patient underwent muscle biopsy within 30 days before Baseline.
  • Patient initiated treatment with a statin or had a significant adjustment to their statin regimen within 3 months before Baseline. (Stable, chronic statin use is permissible.)
  • Patient has received a product that putatively enhances muscle growth (e.g., insulin-like growth factor, growth hormone) or activity (e.g., Coenzyme A) on a chronic basis within 4 weeks before Baseline.
  • Patient is unwilling to abstain from strenuous physical activity for 24 hours prior to each study center visit.
  • Patient previously received ATYR1940.
  • If female and of childbearing potential (premenopausal and not surgically sterile), patient has a positive pregnancy test at Screening or is unwilling to use contraception from the time of Screening through 1 -month after the last Study Drug dose. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device.
  • If male, patient is unwilling to use a condom plus spermicide during sexual intercourse from the time of Screening through 1 -month after the last Study Drug dose.
  • Cohorts ≥2 only: Patient has a known contraindication for MRI assessments (e.g., metal prosthesis or pacemaker) as per local site MRI protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02239224
Other Study ID Numbers  ICMJE ATYR1940-C-002
2014-001753-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party aTyr Pharma, Inc.
Study Sponsor  ICMJE aTyr Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sanjay Shukla, MD aTyr Pharma
PRS Account aTyr Pharma, Inc.
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP