Clinical Trial Results:
A phase III trial investigating the efficacy and safety of Grazax in children aged 5-16 years with grass pollen induced rhinoconjunctivitis with or without asthma
Summary
|
|
EudraCT number |
2006-003415-46 |
Trial protocol |
DE |
Global end of trial date |
21 Sep 2007
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
16 Feb 2016
|
First version publication date |
26 Jul 2015
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
GT-12
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
ALK-Abelló
|
||
Sponsor organisation address |
Bøge Allé 1, Hørsholm, Denmark, 2970
|
||
Public contact |
Clinical Development, ALK-Abelló, +45 4574 7576, ClinicalTrials@alk.net
|
||
Scientific contact |
Clinical Development, ALK-Abelló, +45 4574 7576, ClinicalTrials@alk.net
|
||
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 |
21 Sep 2007
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
21 Sep 2007
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
21 Sep 2007
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To evaluate the efficacy and safety of specific immunotherapy with Grazax compared to placebo, in children with grass pollen induced allergic rhinoconjunctivitis.
|
||
Protection of trial subjects |
Safety surveillance
Use of symptomatic medications allowed
|
||
Background therapy |
Rescue Medication Rhinoconjunctivitis: Loratadine tablets (10 mg), levocabastine eye drops (0.5 mg/ml), budesonide nasal spray (50 μg), prednisolone tablets (5 mg). Asthma: Salbutamol inhaler or spray (0.10%), fluticasone inhaler or spray (125 or 250 μg), prednisolone tablets (5 mg). | ||
Evidence for comparator |
Placebo comparator | ||
Actual start date of recruitment |
22 Nov 2006
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 253
|
||
Worldwide total number of subjects |
253
|
||
EEA total number of subjects |
253
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
140
|
||
Adolescents (12-17 years) |
113
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
253 subjects were recruited by 26 investigators in Germany | |||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
307 subjects were screened, 54 were screening failures | |||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
Placebo tablets were similar to the Grazax tablets as regards appearance, smell and taste.
|
|||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Sublingual tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Sublingual use
|
|||||||||||||||||||||||||||
Dosage and administration details |
1 fast-disolving tablet per day
|
|||||||||||||||||||||||||||
Arm title
|
Grazax | |||||||||||||||||||||||||||
Arm description |
Active treatment | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Grazax
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
SQ grass SLIT-tablet
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Sublingual tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Sublingual use
|
|||||||||||||||||||||||||||
Dosage and administration details |
1 fast-disolving tablet per day
|
|||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Grazax
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Active treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
- | ||
Reporting group title |
Grazax
|
||
Reporting group description |
Active treatment |
|
|||||||||||||
End point title |
Rhinoconjunctivitis Symptom Score | ||||||||||||
End point description |
A total of 6 rhinoconjunctivitis symptoms were evaluated on a scale of 0 to 3, as follows:
0 No symptoms
1 Mild symptoms
2 Moderate symptoms
3 Severe symptoms
Nose symptoms: Runny nose, Blocked nose, Sneezing, Itchy nose
Eye symptoms: Gritty feeling / red/itchy eyes, Watery eyes
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
during the grass pollen season
|
||||||||||||
|
|||||||||||||
Notes [1] - all who provided diary data during the grass pollen season [2] - all who provided diary data during the grass pollen season |
|||||||||||||
Statistical analysis title |
Analysis of average rhinoconjunctivitis symptom sc | ||||||||||||
Statistical analysis description |
Parametric analysis: ANOVA, square-root-transformed data, adjusted means with 95% confidence intervals backtransformed
by squaring
|
||||||||||||
Comparison groups |
Placebo v Grazax
|
||||||||||||
Number of subjects included in analysis |
238
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0215 | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.62
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.1 | ||||||||||||
upper limit |
1.15 | ||||||||||||
Variability estimate |
Standard deviation
|
|
|||||||||||||
End point title |
Rhinoconjunctivitis medication score | ||||||||||||
End point description |
The average daily rhinoconjunctivitis medication scores over the entire grass pollen season
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
During the entire grass pollen season
|
||||||||||||
|
|||||||||||||
Notes [3] - Subjects with diary data during the grass pollen season [4] - Subjects with diary data during the grass pollen season |
|||||||||||||
Statistical analysis title |
Analysis of average rhinoconjunctivitis medication | ||||||||||||
Statistical analysis description |
Analysis of average rhinoconjunctivitis medication score, entire grass pollen season (FAS)
|
||||||||||||
Comparison groups |
Placebo v Grazax
|
||||||||||||
Number of subjects included in analysis |
238
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [5] | ||||||||||||
P-value |
= 0.0156 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Hodges-Lehmann estimate | ||||||||||||
Point estimate |
0.31
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.01 | ||||||||||||
upper limit |
0.68 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
Notes [5] - A parametric ANOVA could not be performed for the average rhinoconjunctivitis medication score, since neither the untransformed data, nor transformed data fulfilled the assumption of normal distribution. A non-parametric analysis was performed using the Wilcoxon rank sum test. |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From signing of informed consent to end of trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
6.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Grazax
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Active treatment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
26 Oct 2006 |
pre-trial - incorporation of comments given by competent authorities |
||
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. | |||
Not applicable | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/19130937 |