Clinical Trial Results:
Investigation of the protective effects of keratinocyte growth factor (KGF) in a human lipopolysaccharide induced model of acute lung injury
Summary
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EudraCT number |
2008-000441-58 |
Trial protocol |
GB |
Global end of trial date |
09 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Feb 2020
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First version publication date |
08 Feb 2020
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Other versions |
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Summary report(s) |
Figures from publication Figures from supplementary section of publication Am J Respir Crit Care Med publication |
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 |
08005DM-A
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Additional study identifiers
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ISRCTN number |
ISRCTN98813895 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Belfast Health & Social Care Trust (BHSCT)
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Sponsor organisation address |
King Edward Building, Royal Hospitals, Grosvenor Road, Belfast, United Kingdom, BT12 6BA
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Public contact |
Prof Daniel McAuley, Queen's University of Belfast, 02890 976385, d.f.mcauley@qub.ac.uk
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Scientific contact |
Prof Daniel McAuley, Queen's University of Belfast, 02890 976385, d.f.mcauley@qub.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 |
17 Nov 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Nov 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Apr 2015
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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 hypothesis of the study is that treatment with a clinically relevant dose of KGF reduces pulmonary and systemic inflammation induced by LPS inhalation in humans.
The primary endpoint of this study is to evaluate the ability of KGF to reduce alveolar epithelial injury, as measured by BAL RAGE concentration, between the KGF and placebo treated groups.
All outcomes are BAL.
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Protection of trial subjects |
A DMEC was appointed which was independent of the study team. The DMEC met to agree conduct and remit which included an early termination process. The DMEC functioned primarily as a check for safety, reviewing adverse events. The DMEC reported to the Sponsor via the principal investigator.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
08 Aug 2008
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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: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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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) |
39
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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 |
Healthy subjects were recruited by advertising. | |||||||||||||||
Pre-assignment
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Screening details |
Screening consisting of a questionnaire, physical examination, routine blood investigation, ECG, and measurement of lung function with spirometry (FEV1 and FVC) was performed. | |||||||||||||||
Period 1
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Period 1 title |
Overall trial (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, Monitor, Assessor | |||||||||||||||
Blinding implementation details |
When an eligible subject was recruited, the clinical trials pharmacist was contacted with the
subject details. The medication was prepared by the pharmacist according to guidance in a covered syringe thereby maintaining blinding. Both the active and placebo treatment had an identical appearance.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Keratinocyte growth factor (KGF) | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Keratinocyte growth factor
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Investigational medicinal product code |
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Other name |
palifermin
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
60 μg/kg per day for 3 days
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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 |
Intravenous bolus use
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Dosage and administration details |
3 days
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Arm title
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Placebo | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
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 |
Intravenous bolus use
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Dosage and administration details |
3 days
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Baseline characteristics reporting groups
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Reporting group title |
Keratinocyte growth factor (KGF)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Keratinocyte growth factor (KGF)
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- |
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End point title |
RAGE | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
RAGE comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.11 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
WBC count | ||||||||||||
End point description |
white blood count
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
WBC count comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
albumin | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
albumin comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-1Ra | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
IL-1Ra comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.011 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-1b/IL-1Ra ratio | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
IL-1b/IL-1Ra ratio comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.009 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-1b | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
IL-1b comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
TNF-a | ||||||||||||
End point description |
tumor necrosis factor
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
TNF-a comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-6 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after inhalation
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Statistical analysis title |
IL-6 comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-8 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
IL-8 comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
VEGF | ||||||||||||
End point description |
vascular endothelial growth factor
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
VEGF comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
MCP-1 | ||||||||||||
End point description |
monocyte chemoattractant protein
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End point type |
Secondary
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End point timeframe |
24 hours after inhalation
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Statistical analysis title |
MCP-1 comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
HMGB1 | ||||||||||||
End point description |
high-mobility group box 1
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
HMGB1 comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Calgranulin C | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
Calgranulin C comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
CRP | ||||||||||||
End point description |
C-reactive protein
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End point type |
Secondary
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End point timeframe |
24 hours after LPS inhalation
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Statistical analysis title |
CRP comparison of groups | ||||||||||||
Comparison groups |
Keratinocyte growth factor (KGF) v Placebo
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
> 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
24 hours after LPS inhalation
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Keratinocyte growth factor (KGF)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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27 Dec 2008 |
To source the study medication from Biovitrum |
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22 Jan 2009 |
To increase the number of volunteers undergoing bronchoscopy and BAL from 5 to 10; to recruit 5 volunteers who undergo bronchoscopy and BAL after pre treatment with 3 days for KGF at a dose of 60 microgram/kg; to isolate alveolar macrophages from BAL and study them in vitro
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30 Dec 2009 |
To measure the serine protease and anti protease activity in plasma samples |
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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. An additional 15 control subjects were enrolled. In keeping with the study protocol these subjects were not randomised to receive IMP. In addition to the Endpoints section, other outcomes are presented graphically in the attachments. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/24716610 |