Clinical Trial Results:
A randomised double-blind placebo-controlled Phase 2B clinical trial of repeated application of gene therapy in patients with cystic fibrosis
Summary
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EudraCT number |
2011-004761-33 |
Trial protocol |
GB |
Global end of trial date |
30 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jun 2019
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First version publication date |
08 Jun 2019
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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
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Sponsor protocol code |
CRO1881
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
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 |
1b Manresa road, London, United Kingdom, SW3 6LR
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Public contact |
Samia Soussi, Imperial College, +44 2075947980, s.soussi@imperial.ac.uk
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Scientific contact |
Samia Soussi, Imperial College, +44 2075947980, s.soussi@imperial.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 |
02 Jul 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
30 May 2014
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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 clinical study has three main objectives:
1. To assess the clinical benefit of pGM169/GL67A when administered on a monthly basis over a period of a year.
2. To assess the safety and tolerability of pGM169/GL67A over the same period.
3. To assess gene expression directed by pGM169/GL67A over the same period.
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Protection of trial subjects |
Subjects fully informed prior to enrolment
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Jan 2012
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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: 116
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Worldwide total number of subjects |
116
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EEA total number of subjects |
116
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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) |
40
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Adults (18-64 years) |
76
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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 |
Pre-dosing visits (all patients or selected ones as indicated) - Eligibility & Consent (E&C) visit (selected nPD or bronchoscopy subjects only - Introductory visit (optional, if required for new, non-Run In study subjects only) - Screening visit (all subjects) - Pre-dosing nasal PD visits x up to3 (nasal subgroup only- may be before or after Sc | |||||||||
Pre-assignment
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Screening details |
Screening visit This will involve: Page 18 of 52 Repeated application of gene therapy in CF patients; v06; 21/08/2013 confirmation that patient fulfils inclusion/ exclusion criteria informed consent signed (if no Introductory Visit) quality of life questionnaire full medical history and physical examination including heart rate, resp | |||||||||
Pre-assignment period milestones
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Number of subjects started |
116 | |||||||||
Number of subjects completed |
116 | |||||||||
Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo group | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
0.9% Saline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nebuliser solution, Nasal spray, solution, Nebuliser suspension
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Routes of administration |
Nasal use, Inhalation use
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Dosage and administration details |
Administration of 5 ml placebo (0.9% saline) via nebuliser to the lungs every 4 weeks for 12 doses
Administration of 2 ml placebo (0.9% saline) via nasal spray to the nose every 4 weeks for 12 doses (subgroup only)
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Arm title
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pGM169/GL67A group | |||||||||
Arm description |
- | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
pGM169/GL67A
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution, Nebuliser solution, Nebuliser suspension
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Routes of administration |
Inhalation use, Nasal use
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Dosage and administration details |
Administration of 5 ml pGM169/GL67A via nebuliser to the lungs every 4 weeks for 12 doses
Administration of 2 ml pGM169/GL67A via nasal spray to the nose every 4 weeks for 12 doses (subgroup only)
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Baseline characteristics reporting groups
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Reporting group title |
Placebo group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
pGM169/GL67A group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo group
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Reporting group description |
- | ||
Reporting group title |
pGM169/GL67A group
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Reporting group description |
- | ||
Subject analysis set title |
Treatment effect
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment effect in pGM169/GL67A group versus placebo group
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Subject analysis set title |
Treatment effect
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Treatment effect in pGM169/GL67A group versus placebo group
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End point title |
FEV1 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Absolute treatment effect
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Statistical analysis title |
ANCOVA-adjusted treatment effect | ||||||||||||
Statistical analysis description |
ANCOVA-adjusted treatment effect in the pGM169/GL67A group versus Placebo at 12 months follow up
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Comparison groups |
Treatment effect v Treatment effect
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.046 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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End point title |
FVC | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
MEF 25-75 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
Lung clearence index | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Bronchiectasis extent | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Bronchiectasis severity | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Wall thickness | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Large airway mucus plugs | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Small airway mucus plugs | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
CT Gas trappings | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
C-reactive protein | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
Erythrocyte sedimentation rate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
White blood cells | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
KCOc | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
TLCOc | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
Alveolar volume | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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No statistical analyses for this end point |
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End point title |
Sputum 24h weight | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Absolute treatment effect
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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 |
Post dose
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Placebo group
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Reporting group description |
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Reporting group title |
pGM169/GL67A group
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
None reported |