Clinical Trial Results:
IMMUNOGENICITY AND SAFETY OF THE JAPANESE ENCEPHALITIS VACCINE IC51 (IXIARO®, JESPECT®) IN A PEDIATRIC POPULATION IN NON‐ENDEMIC COUNTRIES. UNCONTROLLED, OPEN‐LABEL PHASE 3 STUDY.
|
Summary
|
|
EudraCT number |
2009-015595-10 |
Trial protocol |
DE SE DK |
Global end of trial date |
09 Aug 2013
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
31 Jan 2016
|
First version publication date |
31 Jan 2016
|
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 |
IC51-322
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01047839 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Valneva Austria GmbH
|
||
Sponsor organisation address |
Campus Vienna Biocenter 3, Vienna, Austria, 1030
|
||
Public contact |
Clinical Operations, Valneva Austria GmbH, 0043 1206200, info@valneva.com
|
||
Scientific contact |
Clinical Operations, Valneva Austria GmbH, 0043 1206200, info@valneva.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000559-PIP01-09 | ||
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? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
10 Oct 2013
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Aug 2013
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Assessment of the safety profile of IC51 vaccine in a pediatric population from regions where Japanese Encephalitis is not endemic.
|
||
Protection of trial subjects |
An independent Data Safety Monitoring Board (DSMB) reviewed safety data after 44 subjects had received their first vaccination. The subject’s legal representative or the subject, as applicable, was asked to report all symptoms (solicited and unsolicited AEs) after vaccination with IC51.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Feb 2010
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
36 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Sweden: 4
|
||
Country: Number of subjects enrolled |
Denmark: 1
|
||
Country: Number of subjects enrolled |
Germany: 36
|
||
Country: Number of subjects enrolled |
Australia: 19
|
||
Country: Number of subjects enrolled |
United States: 40
|
||
Worldwide total number of subjects |
100
|
||
EEA total number of subjects |
41
|
||
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) |
7
|
||
Children (2-11 years) |
34
|
||
Adolescents (12-17 years) |
59
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||
Recruitment details |
Subjects were recruited in 11 study centers located in Australia, EU (Germany, Denmark, Sweden) and the United States. Recruitment started on 24-Feb-2010 and was completed on 24-Jan-2013. | |||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||
Screening details |
Uncontrolled, open-label Phase 3 study in children aged ≥ 2 months to < 18 years planning to travel to countries where JE is endemic and JE vaccination would be recommended. | |||||||||||||||||||||
|
Period 1
|
||||||||||||||||||||||
Period 1 title |
Overall study (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
|
Arm title
|
IC51 0.25 ml group | |||||||||||||||||||||
Arm description |
Safety and Immunogenicity follow-up to M7 | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
IC51
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||
Dosage and administration details |
Subjects aged ≥ 2 months to < 3 years received 2 vaccinations of 0.25 ml IC51 at an interval of 4 weeks (Day 0 and 28).
|
|||||||||||||||||||||
|
Arm title
|
IC51 0.5 ml group | |||||||||||||||||||||
Arm description |
Safety and Immunogenicity follow-up to M7 | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
IC51
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||
Dosage and administration details |
Subjects aged ≥ 12 to < 18 years received 2 vaccinations of 0.5 ml IC51 at an interval of 4 weeks (Day 0 and 28).
|
|||||||||||||||||||||
|
||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall study
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
IC51 0.25 ml group
|
||
Reporting group description |
Safety and Immunogenicity follow-up to M7 | ||
Reporting group title |
IC51 0.5 ml group
|
||
Reporting group description |
Safety and Immunogenicity follow-up to M7 | ||
|
|||||||||||||
End point title |
Rate of subjects with SAEs and medically attended AEs up to Day 56 after the first vaccination. [1] | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
56 Days after the first IC51 vaccination.
|
||||||||||||
| 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: Analysis of the primary endpoint was descriptive, i.e. no statistical hypothesis test was performed. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Rate of subjects with SAEs and medically attended AEs up to Month 7 after the first vaccination. | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
7 Months after the first IC51 vaccination.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
AEs were recorded at all study visits until Month 7.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All subjects who were enrolled in the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
||
06 May 2010 |
Amendment 1/Amendment 2: Age limit for subjects was lowered from 6 months to 2 months. Minimum recruitment numbers for each age group were stipulated. Exclusion criterion 3 was amended to ease inclusion of children less than 6 months old with dense childhood immunization schedules (all Amendment 1). Timing of Visit 0 (Screening) and Visit 1 were amended to allow for a combined visit. Exclusion criteria 1 and 3 were amended to include history of any Flavivirus disease and to harmonize forbidden concomitant active or passive vaccination during the treatment period for all age groups. Relevant protocol deviations which might be noticed after the first vaccination were specified in more detail. Number of subjects in each age group was further clarified (all Amendment 2). |
||
16 Dec 2010 |
Amendment 3: Consolidation of local amendments in Australia and Sweden. Results of the dose finding run-in phase from Study IC51-323 were added to the Introduction and the appropriate dose for subjects aged ≥ 3 to < 12 years added throughout the protocol. In case of a combined visit (Visit 0 and Visit 1) the pregnancy testing was amended. |
||
20 May 2011 |
Amendment 4: Removal of age-stratification for an enrollment of 100 children aged ≥ 2 months to < 18 years. Initial planned suspension of enrollment during the DSMB review was amended to allow enrollment during the review. |
||
05 Aug 2011 |
Amendment 5: Non-substantial amendment. Details of an interim analysis were added, which was to be performed on data from all subjects enrolled up to approximately the beginning of July 2011. Details were added on a review of the data by an independent DSMB and the subsequent recommendation. Description of the assay for the assessment of immunogenicity was updated. |
||
31 Oct 2011 |
Amendment 6: Primary objective and primary endpoint were changed from immunogenicity to safety, with immunogenicity assessments limited to children enrolled under previous protocol versions (up to Protocol Version 9.0). Statistical analysis details and pre‐specified subgroup analysis were adjusted to accommodate the changes to the objectives and endpoints, minimum number of subjects with immunogenicity data evaluable was set to 50. Time window for performing the first follow‐up visit, Visit 3, was widened to a minimum of 7 days to a maximum of 2 months after Visit 2 (Day 28). Details of Visit 3 were amended to allow the visit to be conducted face-to-face or as a telephone call and, if the latter, to permit the subject diary to be mailed to the site. Inclusion criterion specifying the timing of travel was amended to accommodate the change to Visit 3. Interim safety results of the DSMB review were included. |
||
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. | |||
| As the number of subjects in the 0.25 mL dose group was low, a meaningful comparison between the 2 dose groups is not possible. | |||
