Clinical Trial Results:
Safety of Two Doses of Avaxim® 80U Pediatric (Inactivated Hepatitis A vaccine) Administered 6 Months Apart in Healthy Toddlers, Children and Adolescents Aged 12 Months to 15 Years in China
Summary
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EudraCT number |
2015-003190-14 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
10 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Jun 2016
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First version publication date |
17 Jun 2016
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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 |
HAF87
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02011763 | ||
WHO universal trial number (UTN) |
U1111-1127-7652 | ||
Sponsors
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Sponsor organisation name |
Sanofi Pasteur SA
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Sponsor organisation address |
2, avenue Pont Pasteur, Lyon cedex 07, France, F-69367
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Public contact |
Responsible Medical Officer, Sanofi Pasteur SA, 33 04 37 37 7384, eric.desauziers@sanofipasteur.com
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Scientific contact |
Responsible Medical Officer, Sanofi Pasteur SA, 33 04 37 37 7384, eric.desauziers@sanofipasteur.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 |
21 Apr 2015
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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 |
10 Oct 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 |
To describe the safety of Avaxim 80U Pediatric vaccine after each dose of vaccine administered 6 months apart, in subjects aged 12 months to 15 years.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were enrolled and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
06 Dec 2013
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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 |
China: 355
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Worldwide total number of subjects |
355
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EEA total number of subjects |
0
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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) |
270
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Children (2-11 years) |
51
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Adolescents (12-17 years) |
34
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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 |
Study subjects were enrolled from 06 December 2013 to 11 February 2014 at 1 clinic center in China. | ||||||||||||||||||
Pre-assignment
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Screening details |
A total of 355 subjects who met all inclusion and none of the exclusion criteria were enrolled and vaccinated in this trial. | ||||||||||||||||||
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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Avaxim® 80U Pediatric Group 1 | ||||||||||||||||||
Arm description |
Infants and toddlers (≤ 23 months) received 2 injections of Avaxim® 80U Pediatric vaccine 6 months apart. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Avaxim® 80U Pediatric
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5 mL, intramuscular, 1 injection each on Day 0 and Day 180.
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Arm title
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Avaxim® 80U Pediatric Group 2 | ||||||||||||||||||
Arm description |
Children (aged 2 to 11 years) and adolescents (aged 12 to 15 years) received 2 injections of Avaxim® 80U Pediatric vaccine. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Avaxim® 80U Pediatric
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5 mL, intramuscular, 1 injection each on Day 0 and Day 180.
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Baseline characteristics reporting groups
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Reporting group title |
Avaxim® 80U Pediatric Group 1
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Reporting group description |
Infants and toddlers (≤ 23 months) received 2 injections of Avaxim® 80U Pediatric vaccine 6 months apart. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Avaxim® 80U Pediatric Group 2
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Reporting group description |
Children (aged 2 to 11 years) and adolescents (aged 12 to 15 years) received 2 injections of Avaxim® 80U Pediatric vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Avaxim® 80U Pediatric Group 1
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Reporting group description |
Infants and toddlers (≤ 23 months) received 2 injections of Avaxim® 80U Pediatric vaccine 6 months apart. | ||
Reporting group title |
Avaxim® 80U Pediatric Group 2
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Reporting group description |
Children (aged 2 to 11 years) and adolescents (aged 12 to 15 years) received 2 injections of Avaxim® 80U Pediatric vaccine. |
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End point title |
Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions After Any Vaccination with AVAXIM™ 80U-Pediatric Vaccine [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited inj. site reactions: Tenderness, Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, Irritability, Headache, Malaise, and Myalgia.
Grade 3 inj. site reactions: Tenderness (≤ 23 months), Cries when injected limb is moved or the movement of the injected limb is reduced; Pain (2 to 11 years), Incapacitating, unable to perform usual activities; Pain (≥ 12 years), Significant, prevents daily activity; Erythema and Swelling (China Food and Drug Administration; CFDA), > 30 mm. Grade 3 systemic reactions (≤ 23 months): Fever (CFDA), > 39.0°C; Vomiting, ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥ 3 feeds or refuses most feeds; Irritability, Inconsolable. Grade 3 systemic reactions (≥ 2 years): Fever (CFDA), > 39.0°C; Headache, Malaise, and Myalgia, Significant, prevents daily activity
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 7 post-any dose
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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 analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions After First Dose Vaccination with AVAXIM™ 80U-Pediatric Vaccine [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited inj. site reactions: Tenderness, Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, Irritability, Headache, Malaise, and Myalgia.
Grade 3 inj. site reactions: Tenderness (≤ 23 months), Cries when injected limb is moved or the movement of the injected limb is reduced; Pain (2 to 11 years), Incapacitating, unable to perform usual activities; Pain (≥ 12 years), Significant, prevents daily activity; Erythema and Swelling (China Food and Drug Administration; CFDA), > 30 mm. Grade 3 systemic reactions (≤ 23 months): Fever (CFDA), > 39.0°C; Vomiting, ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥ 3 feeds or refuses most feeds; Irritability, Inconsolable. Grade 3 systemic reactions (≥ 2 years): Fever (CFDA), > 39.0°C; Headache, Malaise, and Myalgia, Significant, prevents daily activity
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 7 post-dose 1
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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 analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions After Second Dose Vaccination with AVAXIM™ 80U-Pediatric Vaccine [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited inj. site reactions: Tenderness, Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, Irritability, Headache, Malaise, and Myalgia.
Grade 3 inj. site reactions: Tenderness (≤ 23 months), Cries when injected limb is moved or the movement of the injected limb is reduced; Pain (2 to 11 years), Incapacitating, unable to perform usual activities; Pain (≥ 12 years), Significant, prevents daily activity; Erythema and Swelling (China Food and Drug Administration; CFDA), > 30 mm. Grade 3 systemic reactions (≤ 23 months): Fever (CFDA), > 39.0°C; Vomiting, ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥ 3 feeds or refuses most feeds; Irritability, Inconsolable. Grade 3 systemic reactions (≥ 2 years): Fever (CFDA), > 39.0°C; Headache, Malaise, and Myalgia, Significant, prevents daily activity
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 7 post-dose 2
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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 analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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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 |
Adverse event data were collected from Day 0 up to Day 7 post-dose 2.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Infants and toddlers (≤ 23 months) who received 2 injections of Avaxim® 80U Pediatric vaccine 6 months apart. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Children (aged 2 to 11 years) and adolescents (aged 12 to 15 years) who received 2 injections of Avaxim® 80U Pediatric vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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01 Feb 2014 |
Clarification of interim/preliminary statistical analyses and timelines. |
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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. | |||
A sponsor’s QC visit found 22 Diary Cards had similar handwriting. A site staff filled the cards based on discussion with the subjects. A subset analysis without the 22 subjects was done. Outcome is comparable to results of full safety analysis set. |