Prove cliniche Nct
Clinical Trial Results:
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
| Summary | |
EudraCT number | 2014-003346-27 |
Trial protocol | IT |
Global end of trial date | 14 Feb 2017 |
| Results information | |
Results version number | v1(current) |
This version publication date | 20 May 2018 |
First version publication date | 20 May 2018 |
Other versions | |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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| Trial identification | |||
Sponsor protocol code | ATYR1940-C-003 | ||
| Additional study identifiers | |||
ISRCTN number | - | ||
US NCT number | - | ||
WHO universal trial number (UTN) | - | ||
Other trial identifiers | IND number: 122045 | ||
| Sponsors | |||
Sponsor organisation name | aTyr Pharma, Inc. | ||
Sponsor organisation address | 3545 John Hopkins Court, Suite #250, San Diego, CA, United States, 92121 | ||
Public contact | Clinical Trial Operations, Voisin Consulting, clinicaltrialinformation@voisinconsulting.com | ||
Scientific contact | Clinical Trial Operations, Voisin Consulting, clinicaltrialinformation@voisinconsulting.com | ||
| Paediatric regulatory details | |||
Is trial part of an agreed paediatric investigation plan (PIP) | No | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
| Results analysis stage | |||
Analysis stage | Final | ||
Date of interim/final analysis | 13 Jul 2017 | ||
Is this the analysis of the primary completion data? | Yes | ||
Primary completion date | 14 Feb 2017 | ||
Global end of trial reached? | Yes | ||
Global end of trial date | 14 Feb 2017 | ||
Was the trial ended prematurely? | No | ||
| General information about the trial | |||
Main objective of the trial | To evaluate the safety, tolerability, and immunogenicity of the intravenous (IV) administration of ATYR1940, at doses of 0.3, 1.0, and 3.0 mg/kg, to patients with early onset FSHD | ||
Protection of trial subjects | The study process, benefits and risks of participating in the study were explained to each subject. In addition, if the study drug needed to be stopped for safety, the doctor, his/her staff along with the medical monitor, were to continue to monitor participant's health and determine what treatment should be given (if any) until the symptoms or findings had resolved or until a satisfactory conclusion was reached. | ||
Background therapy | - | ||
Evidence for comparator | - | ||
Actual start date of recruitment | 01 Sep 2015 | ||
Long term follow-up planned | No | ||
Independent data monitoring committee (IDMC) involvement? | Yes | ||
| Population of trial subjects | |||
Number of subjects enrolled per country | |||
Country: Number of subjects enrolled | United States: 5 | ||
Country: Number of subjects enrolled | France: 1 | ||
Country: Number of subjects enrolled | Italy: 2 | ||
Worldwide total number of subjects | 8 | ||
EEA total number of subjects | 3 | ||
Number of subjects enrolled per age group | |||
In utero | 0 | ||
Preterm newborn - gestational age | 0 | ||
Newborns (0-27 days) | 0 | ||
Infants and toddlers (28 days-23 months) | 0 | ||
Children (2-11 years) | 0 | ||
Adolescents (12-17 years) | 3 | ||
Adults (18-64 years) | 5 | ||
From 65 to 84 years | 0 | ||
85 years and over | 0 | ||
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| Recruitment | |||||||||||
Recruitment details | Per the original study design enrollment was to be performed in 2 stages. Stage 1 was conducted and completed and the data are described herein. The sponsor elected not to conduct Stage 2. The key patient disease characteristics included an established genetically confirmed diagnosis of FSHD with FSHD signs or symptoms presenting < 10 years. | ||||||||||
| Pre-assignment | |||||||||||
Screening details | The study actually had 3 periods distinct periods - screening, treatment (13 weeks including 1 dose of placebo at Week 1) and follow-up (12 weeks). | ||||||||||
| Pre-assignment period milestones | |||||||||||
Number of subjects started | 9 [1] | ||||||||||
Number of subjects completed | 8 | ||||||||||
| Pre-assignment subject non-completion reasons | |||||||||||
Reason: Number of subjects | Screen failure: 1 | ||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The worldwide number corresponds to the number of patients randomized (8) and not to the number of patients screened (9). | |||||||||||
| Period 1 | |||||||||||
Period 1 title | Treatment period (overall period) | ||||||||||
Is this the baseline period? | Yes | ||||||||||
Allocation method | Not applicable | ||||||||||
Blinding used | Not blinded | ||||||||||
| Arms | |||||||||||
| Arm title | ATYR1940 | ||||||||||
Arm description | Enrollment into the study was to be conducted in 2 stages, based on patient age. In Stage 1, up to 8 patients between the ages of 16 and 25 years with early onset FSHD who met study entry criteria were enrolled. Stage 2 of enrollment, which was planned to include patients with early onset FSHD between the ages of 12 and 15 years, was to be initiated following an amendment to the study, based on consideration of safety data of ATYR1940 gathered in Stage 1 of this study, along with clinical safety data obtained in other studies of ATYR1940. The Sponsor elected not to conduct Stage 2. | ||||||||||
Arm type | Experimental | ||||||||||
Investigational medicinal product name | ATYR1940 | ||||||||||
Investigational medicinal product code | |||||||||||
Other name | |||||||||||
Pharmaceutical forms | Concentrate for solution for infusion | ||||||||||
Routes of administration | Intravenous use | ||||||||||
Dosage and administration details | Three dose levels of ATYR1940 were to be evaluated using intrapatient dose escalation: 0.3, 1.0, and 3.0 mg/kg. Following a single, 90-minute IV placebo (normal saline Week 1) infusion, ATYR1940 was to be administered as a 90-minute IV infusion once a week for 12 weeks, starting at a dose of 0.3 mg/kg, with the potential for intrapatient dose escalation over the dosing period. During the 13-week treatment period, patients visited the clinic weekly for dosing and assessments of safety, immunogenicity, and PD activity. Patients also returned to the clinic 1, 4, and 12 weeks after the last dose of ATYR1940 for assessment of safety, immunogenicity, and biological and PD activity. The maximum duration of patient participation in the study was 28 weeks. | ||||||||||
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| Baseline characteristics reporting groups | ||||||||||||||||||||||||||||||||||||||||
Reporting group title | ATYR1940 | |||||||||||||||||||||||||||||||||||||||
Reporting group description | Enrollment into the study was to be conducted in 2 stages, based on patient age. In Stage 1, up to 8 patients between the ages of 16 and 25 years with early onset FSHD who met study entry criteria were enrolled. Stage 2 of enrollment, which was planned to include patients with early onset FSHD between the ages of 12 and 15 years, was to be initiated following an amendment to the study, based on consideration of safety data of ATYR1940 gathered in Stage 1 of this study, along with clinical safety data obtained in other studies of ATYR1940. The Sponsor elected not to conduct Stage 2. | |||||||||||||||||||||||||||||||||||||||
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| End points reporting groups | |||
Reporting group title | ATYR1940 | ||
Reporting group description | Enrollment into the study was to be conducted in 2 stages, based on patient age. In Stage 1, up to 8 patients between the ages of 16 and 25 years with early onset FSHD who met study entry criteria were enrolled. Stage 2 of enrollment, which was planned to include patients with early onset FSHD between the ages of 12 and 15 years, was to be initiated following an amendment to the study, based on consideration of safety data of ATYR1940 gathered in Stage 1 of this study, along with clinical safety data obtained in other studies of ATYR1940. The Sponsor elected not to conduct Stage 2. | ||
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End point title | Anti-drug antibodies [1] | ||||||
End point description | |||||||
End point type | Primary | ||||||
End point timeframe | Screening and weeks 4, 6, 8, 10, 13, 14, 17 and 25. The visits through week 13 were on-treatment, and visits 14, 17, 25 are post-treatment follow-up. | ||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed for any of the primary/safety endpoints. | |||||||
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| No statistical analyses for this end point | |||||||
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End point title | Anti-Jo1 antibodies [2] | ||||||
End point description | |||||||
End point type | Primary | ||||||
End point timeframe | Screening and weeks 3 to 25 | ||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed for any of the primary/safety endpoints. | |||||||
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| No statistical analyses for this end point | |||||||
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End point title | Heart Rate | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Electrocardiogram - PR Duration | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Electrocardiogram - QRS Duration | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Electrocardiogram - QTcF Interval | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | PFT - FEV1/FVC Ratio | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at week 13 | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Manual Muscle Testing - Overall total score | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Percent change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | INQoL - QoL Score | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Hematocrit | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Hemoglobin | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Erythrocytes | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Leukocytes | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Platelets | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Neutrophils | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Lymphocytes | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Monocytes | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Eosinophils | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Basophils | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Aspartate Aminotransferase | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Alanine Aminotransferase | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Bilirubin | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Blood Urea Nitrogen | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Creatinine | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Creatine Kinase | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Cholesterol | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Sodium | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Potassium | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Bicarbonate | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Calcium | ||||||||
End point description | |||||||||
End point type | Secondary | ||||||||
End point timeframe | Change from baseline at 1-week post-treatment follow-up | ||||||||
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| No statistical analyses for this end point | |||||||||
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| Adverse events information | |||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events | Throughout the study | ||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description | TEAEs reported for ≥ 2 patients treated with ATYR1940 are listed in the section below. The number of occurrences per TEAE is not available in the source data, the field "Occurrences all number" therefore corresponds to the number of subjects affected per TEAE. | ||||||||||||||||||||||||||||||||||||||||||||
Assessment type | Systematic | ||||||||||||||||||||||||||||||||||||||||||||
| Dictionary used for adverse event reporting | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary name | MedDRA | ||||||||||||||||||||||||||||||||||||||||||||
Dictionary version | 18.1 | ||||||||||||||||||||||||||||||||||||||||||||
| Reporting groups | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | ATYR1940 | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | - | ||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) | |||
| Were there any global substantial amendments to the protocol? Yes | |||
Date | Amendment | ||
12 Jan 2016 | Protocol version 2.0 dated 12 January 2016 | ||
Interruptions (globally) | |||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats | |||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||