Clinical Trial Results:
A phase 2a study to explore treatment with Sodium Valproate in adults with McArdle Disease (Glycogen Storage Disorder Type V, GSDV)
Summary
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EudraCT number |
2014-001637-88 |
Trial protocol |
DK |
Global end of trial date |
10 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Mar 2021
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First version publication date |
26 Mar 2021
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Other versions |
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Summary report(s) |
Journal article Results file |
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
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Sponsor protocol code |
2014-650
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03112889 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
John Vissing
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Sponsor organisation address |
Blegdamsvej 9, Copenhagen, Denmark, 2100
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Public contact |
Neuromuscular research unit, Neuromuscular research unit, Rigshospitalet, 0045 35456135,
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Scientific contact |
Neuromuscular research unit, Neuromuscular research unit, Rigshospitalet, 0045 35456135,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Dec 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Investigate whether sodium valproate can improve muscle functioning in subjects with McArdle Disease (Glycogen storage disease type V)
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Protection of trial subjects |
Measures to protect patients included avoidance of pre-treatment muscle biopsy if the patient had previously had one performed. Regular trial monitoring was done on the part of the sponsor. Rapid notification of SAE. All subjects were given emergency contact details of the CI and investigators and regular telephone contact with the subjects was maintained during the trial between study visits.
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Background therapy |
No specific background therapy apart from study-drug | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Mar 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
6
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
10 subjects were contacted to take part in this clinical trial. All patients were attending a highly specialized service for neuromuscular disorders including McArdle disease at Rigshospitalet, Copenhagen, Denmark. Recruitment started in October 2015 and last subject was recruited in June 2016. | ||||||||||||
Pre-assignment
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Screening details |
8 patients were screened, 0 were not eligible. 6 subjects completed the study, 4 male and 2 females. Mean age of included subjects was 45 years (range 21-66, SD 18). | ||||||||||||
Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Not applicable (open-label study)
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Arms
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Arm title
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Overall study arm | ||||||||||||
Arm description |
Open-label study of one study arm. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Sodium Valproate
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Investigational medicinal product code |
VPA
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Modified release VPA was prescribed at a treatment dose of 20 mg/kg/day. The dose was rounded up or down to the nearest value dependent on weight.
VPA dose was titrated over 4 weeks from a starting dose of 5 ml/kg/day to the treatment dose of 20mg/kg/day in order to minimise side effects.
At the end of the study VPA was titrated down over 4 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Overall period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall study arm
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Reporting group description |
Open-label study of one study arm. |
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End point title |
Peak oxygen uptake (VO2peak) [1] | ||||||||
End point description |
Subjects performed exercise on a bike ergometer. Oxygen consumption was assessed by a face mask attached to a cardiopulmonary exercise training gas exchange analyser (Cosmed, Milan, Italy). An incremental exercise test was performed during the screening visit (20 watts baseline workload, with 5W increments every 2 minutes) to determine peak oxygen uptake (VO2peak). Heart rate was monitored during exercise by using a 3-lead cardiac monitor and rating of perceived exertion (RPE) were recorded every minute. Maximal workload was the highest attained workload at end of exercise (if held for at least 60 seconds).
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End point type |
Primary
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End point timeframe |
Change from baseline to post 28 weeks treatment.
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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 analyses for this end-point. Trial is a descriptive open-label feasibility trial. The aim of the trial is to provide information on whether a larger-scale trial is possible and if so data from this trial will be used to estimate parameters for making a well-informed power-calculation in a future randomized clinical trial. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
AE documented at week 16 and 28. SAE reported within 24 hours.
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Adverse event reporting additional description |
AE were assessed as either not IMP-related, possibly IMP-related or probably IMP-related
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
All patients
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Reporting group description |
All included patients, since this was an open label trial. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This study was a small open-label study, statistical analysis was descriptive in scope. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/32811700 |