Clinical Trial Results:
Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: A Phase I/II Clinical Trial Using AVI-4658
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Summary
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EudraCT number |
2006-003833-33 |
Trial protocol |
GB |
Global end of trial date |
31 Mar 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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Other versions |
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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 |
CRO490
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00159250 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
South Kensington Campus, London, United Kingdom, SW7 2AZ
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Public contact |
Francesco Muntoni
, Imperial College London, f.muntoni@ucl.ac.uk
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Scientific contact |
Francesco Muntoni
, Imperial College London, f.muntoni@ucl.ac.uk
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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 |
05 Apr 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2009
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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 |
The purpose of this trial is to evaluate the safety and tolerability of a single intramuscular (IM) dose of AVI-4658, a phosphorodiamidate Morpholino oligomer (PMO) at increasing dosages compared to placebo in up to 9 DMD subjects divided into three groups.
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Protection of trial subjects |
Standard-of-care treatment, including glucocorticoids and cardioprotective drugs, was continued in all patients.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Oct 2007
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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 |
United Kingdom: 7
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Worldwide total number of subjects |
7
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EEA total number of subjects |
7
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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) |
7
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This single-site, non-randomised, single-blind (investigator) study was done at Imperial College NHS Trust, London, UK, in patients with DMD who were recruited nationally. | |||||||||
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Pre-assignment
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Screening details |
Participants were boys with a classic clinical diagnosis of DMD26 who were aged between 10 and 17 years inclusive when the study drug was given. | |||||||||
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Period 1
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Period 1 title |
Treatments (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Low dose AVI-4658 | |||||||||
Arm description |
Low dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AVI-4658
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.09 mg doses were diluted in 900 μL normal saline (0·9%) and injected to the extensor digitorum brevis (EDB) muscle
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
900 μL normal saline injected to the contralateral extensor digitorum brevis (EDB) muscle
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Arm title
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High dose AVI-4658 | |||||||||
Arm description |
High dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AVI-4658
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.9 mg doses were diluted in 900 μL normal saline (0·9%) and injected to the extensor digitorum brevis (EDB) muscle
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
900 μL normal saline injected to the contralateral extensor digitorum brevis (EDB) muscle
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Baseline characteristics reporting groups
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Reporting group title |
Low dose AVI-4658
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Reporting group description |
Low dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High dose AVI-4658
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Reporting group description |
High dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Low dose AVI-4658
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Reporting group description |
Low dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | ||
Reporting group title |
High dose AVI-4658
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Reporting group description |
High dose of AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | ||
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End point title |
Number of participants with adverse events related to AVI-4568 [1] | |||||||||
End point description |
Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Adverse events assessed by light microscopy and immunocytochemistry to detect the differences in inflammatory infiltrates between the AVI-4568 and placebo-treated EDB muscles
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End point type |
Primary
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End point timeframe |
Baseline up to Day 120
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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 due to the low number of participants |
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End point title |
Number of participants with Injection Site Reactions [2] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From the Day of Screening to Day 3
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| 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 analyses due to the low number of participants |
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End point title |
Increased expression of dystrophin | |||||||||
End point description |
Western blot analysis
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End point type |
Secondary
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End point timeframe |
4 weeks
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of participants with Induced Skipping of Exon 51 in the Treated Extensor Digitorum Brevis (EDB) Muscle Determined by Reverse Transcription Polymerase Chain Reaction | |||||||||
End point description |
Sequencing of the RT-PCR products
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End point type |
Secondary
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End point timeframe |
Day 14 to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of participants with Restoration of Dystrophin Protein Expression Measured by Immunocytochemistry | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 14 to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of participants with Restoration of Dystrophin Protein Expression Measured by Western blot analysis | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 14 to Day 28
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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 |
120 days
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Low dose AVI-4658
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Reporting group description |
AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High dose AVI-4658
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Reporting group description |
Participants received a high dose of AVI-4658 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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01 May 2008 |
the investigators had identified considerable comorbidity that precluded recruitment of some of the older patients, it also requested and obtained permission to lower the age at inclusion to 10 years and to be able to recruit ambulant patients. |
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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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/19713152 |
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