Clinical Trial Results:
A Phase III Open, Randomized, Parallel, Multi-Center Study in Children Aged 6 - <36 Months to Compare the Immunogenicity and Safety of a Single 0.5 mL Dose of Inflexal V With a 0.25 mL 2-Dose Regimen of Inflexal V Administered According to a 0/4 Week Schedule and Followed-up for 6 Months
Summary
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EudraCT number |
2010-019745-25 |
Trial protocol |
IT |
Global end of trial date |
29 Jul 2011
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Results information
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Results version number |
v1 |
This version publication date |
06 Jul 2016
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First version publication date |
08 Jul 2015
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Other versions |
v2 |
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 |
INF-V-A005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01229397 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Crucell Switzerland AG
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Sponsor organisation address |
Rehhagstrasse 79, Bern, Switzerland, 3018
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Public contact |
Crucell Switzerland AG, Clinical Registry Group, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Crucell Switzerland AG, Clinical Registry Group, ClinicalTrialsEU@its.jnj.com
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jul 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jul 2011
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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 study was to evaluate the immunogenicity of a single full (0.5 milliliter [mL]) dose and a 0.25 mL 2-dose regime of Inflexal V in unprimed children aged 6 - less than (<) 36 months, using the European Medicines Agency (EMA)/Committee for Medicinal Products for Human Use (CHMP) guideline for the re-registration of the seasonal influenza vaccine in adults (aged greater than or equal to [>=] 18 - less than or equal to [<=] 60 years) as reference.
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Protection of trial subjects |
The participants were observed closely for at least 30 minutes after vaccination with appropriate medical treatment readily available in case of rare anaphylactic reaction Local solicited adverse events (30 min after vaccination) were evaluated by the investigator. Each participant's parents or legal guardians received a Participant Diary and were requested to record all adverse events (AEs) and body temperature on the day of vaccination and on the following 3 days. All AEs, including serious adverse events (SAEs), as well as concomitant medications were evaluated at each visit throughout the study. The parents or legal guardians were instructed to contact the investigator immediately should the participant experience any signs or symptoms they perceive as serious during the period extending from the first study-specific procedure up to and including 6 months after administration of the investigational medicinal product (IMP). The tolerability of the 2 dose regimens of the study vaccine was assessed by the participants' parents/legal guardians and by the investigator 4 weeks after completion of vaccination.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Oct 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Italy: 205
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Worldwide total number of subjects |
205
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EEA total number of subjects |
205
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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) |
85
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Children (2-11 years) |
120
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Adolescents (12-17 years) |
0
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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 |
Recruitment period: 05 October - 17 January 2011; Location: University of Milan | |||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 205 participants were enrolled and treated with Inflexal and included in the all randomized population set. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Inflexal V 0.25 mL x 2 | |||||||||||||||||||||
Arm description |
2 doses of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose: • 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 7.5 μg HA antigen of B/Brisbane/60/2008-like virus | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
INFLEXAL V
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Inflexal V 0.25 milliliter (mL) intramuscular injection twice, 4 weeks apart
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Arm title
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Inflexal V 0.5 mL x 1 | |||||||||||||||||||||
Arm description |
1 dose of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, containing per 0.5 milliliter (mL) dose: • 15 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 15 μg HA antigen of B/Brisbane/60/2008-like virus | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
INFLEXAL V
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Inflexal V 0.5 milliliter (mL) intramuscular injection once only
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Baseline characteristics reporting groups
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Reporting group title |
Inflexal V 0.25 mL x 2
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Reporting group description |
2 doses of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose: • 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 7.5 μg HA antigen of B/Brisbane/60/2008-like virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Inflexal V 0.5 mL x 1
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Reporting group description |
1 dose of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, containing per 0.5 milliliter (mL) dose: • 15 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 15 μg HA antigen of B/Brisbane/60/2008-like virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Inflexal V 0.25 mL x 2 - After 1st Vaccination
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose:
• 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus
• 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus
• 7.5 μg HA antigen of B/Brisbane/60/2008-like virus
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Subject analysis set title |
Inflexal V 0.25 mL x 2 - After 2nd Vaccination
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose:
• 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus
• 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus
• 7.5 μg HA antigen of B/Brisbane/60/2008-like virus
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End points reporting groups
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Reporting group title |
Inflexal V 0.25 mL x 2
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Reporting group description |
2 doses of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose: • 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 7.5 μg HA antigen of B/Brisbane/60/2008-like virus | ||
Reporting group title |
Inflexal V 0.5 mL x 1
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Reporting group description |
1 dose of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, containing per 0.5 milliliter (mL) dose: • 15 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 15 μg HA antigen of B/Brisbane/60/2008-like virus | ||
Subject analysis set title |
Inflexal V 0.25 mL x 2 - After 1st Vaccination
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose:
• 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus
• 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus
• 7.5 μg HA antigen of B/Brisbane/60/2008-like virus
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Subject analysis set title |
Inflexal V 0.25 mL x 2 - After 2nd Vaccination
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose:
• 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus
• 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus
• 7.5 μg HA antigen of B/Brisbane/60/2008-like virus
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End point title |
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the European Medicines Agency (EMA) Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults as Reference [1] | |||||||||||||||||||||
End point description |
Seroprotection rate.
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End point type |
Primary
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End point timeframe |
This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
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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: Descriptive statistics were done and evaluated according to the criteria described in the EMA/CHMP guideline for adults, no inferential statistical analyses were performed. |
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No statistical analyses for this end point |
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End point title |
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the European Medicines Agency (EMA) Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults as Reference [2] | |||||||||||||||||||||
End point description |
Seroconversion rate.
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End point type |
Primary
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End point timeframe |
This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
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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: Descriptive statistics were done and evaluated according to the criteria described in the EMA/CHMP guideline for adults, no inferential statistical analyses were performed. |
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No statistical analyses for this end point |
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End point title |
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the European Medicines Agency (EMA) Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults as Reference [3] | |||||||||||||||||||||
End point description |
GMT-fold increase - calculated as the GMT on Day 22 divided by the baseline GMT value.
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End point type |
Primary
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End point timeframe |
This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
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Notes [3] - 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: Descriptive statistics were done and evaluated according to the criteria described in the EMA/CHMP guideline for adults, no inferential statistical analyses were performed. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With Local and Systemic Adverse Events (AE) as a Measure of Safety and Tolerability [4] | ||||||||||||||||||||||||||||
End point description |
Solicited local and systemic AEs were collected from Day 1 (day of vaccination) to Day 4 inclusive using a subject diary.
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End point type |
Secondary
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End point timeframe |
Solicited local and systemic AEs were collected from Day 1 (day of vaccination) to Day 4 inclusive using a subject diary
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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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 |
Any Adverse event (AE) occurring within 1 month (minimum 28 days) following vaccine administration was recorded. Any serious adverse events (SAE) occurring from study start up to 6 months (at least 180 days) following vaccine administration was recorded.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
Inflexal V 0.25 mL x 2 - After 1st Vaccination
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Reporting group description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose: • 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 7.5 μg HA antigen of B/Brisbane/60/2008-like virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Inflexal V 0.25 mL x 2 - After 2nd Vaccination
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Reporting group description |
Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, 4 weeks apart, containing per 0.25 milliliter (mL) dose: • 7.5 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 7.5 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 7.5 μg HA antigen of B/Brisbane/60/2008-like virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Inflexal V 0.5 mL x 1
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Reporting group description |
1 dose of Inflexal V influenza vaccine (surface antigen, inactivated, virosome) 2010/2011, containing per 0.5 milliliter (mL) dose: • 15 microgram (μg) HA antigen of A/California/7/2009 (H1N1)-like virus • 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus • 15 μg HA antigen of B/Brisbane/60/2008-like virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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03 Jun 2010 |
The overall reason for the amendment was to introduced a 6 month follow-up visit for the participants enrolled in the study, at which an additional blood sample for immunogenicity evaluation was taken. |
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20 Dec 2010 |
The overall reason for the amendment was to change the principal investigator. |
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06 May 2011 |
The overall reason for the amendment was to establish second interim analysis after immunogenicity data for the follow-up visit at Day 212 (plus [+] or minus [-] 7 days) had become available for at least 70 participants in each study arm. |
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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 |