Clinical Trial Results:
A Phase IIIb, Controlled, Open Label, Single-Center, Persistency, Extension study in Chinese children after a 2 + 1 dose series of either CRM197- conjugate Haemophilus influenzae type b vaccine or tetanus toxoid-conjugate Haemophilus influenzae type b vaccine
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Summary
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EudraCT number |
2015-001453-32 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
29 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Dec 2016
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First version publication date |
28 Jun 2015
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Other versions |
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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 |
V37_07E2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02139228 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics Srl
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Sponsor organisation address |
Via Fiorentina, 1, Siena, Italy, 53100
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Public contact |
Posting Director, Novartis Vaccines and Diagnostics Srl, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting Director, Novartis Vaccines and Diagnostics Srl, RegistryContactVaccinesUS@novartis.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 |
05 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jan 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 |
Immunogenicity Objective:
To assess anti- PRP antibodies persistency in children participating in previous V37_07E1 trial (EUDRACT number:2014-005135-13), approximately 4 years after booster vaccination with either Hib-CRM197 or Hib-TT.
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Protection of trial subjects |
This study was conducted in accordance with relevant requirements specified in Provisions for Drug Registration (PDR), Good Clinical Practice (GCP), GCP for vaccine trials issued by the CFDA. The Technical Guidelines on Clinical Trial of Vaccine were executed by closely following the principles of the Helsinki Declaration. The trial was performed under the organization of Hebei Center for Disease Control, and its trial protocol, along with relevant documents, was approved by the Ethics Committee of Hebei Center for Disease Control on 21 APR 14 after review. The study was conducted by scientifically and medically qualified persons; and each subject’ parents or legal guardian signed the Informed Consent Form before any protocol procedure was performed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Nov 2014
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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: 426
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Worldwide total number of subjects |
426
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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) |
0
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Children (2-11 years) |
426
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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 |
One centre in China | |||||||||
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Pre-assignment
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Screening details |
All subjects enrolled into the parent V37_07E1 (EUDRACT number:2014-005135-13) study were invited to participate in the trial | |||||||||
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Period 1
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Period 1 title |
Enrolled (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Hib CRM197 | |||||||||
Arm description |
Subjects treated with 3 doses of CRM 197 –conjugate Haemophilus influenzae type b vaccine (study vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | |||||||||
Arm type |
no product administered | |||||||||
Investigational medicinal product name |
No product was administered in this extension study
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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 |
Route of administration not applicable
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Arm title
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Hib TT | |||||||||
Arm description |
Subjects treated with 3 doses of Tetanus Toxoid-conjugate Haemophilus influenzae type b vaccine (comparator vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | |||||||||
Arm type |
no product administered | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Hib CRM197
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Reporting group description |
Subjects treated with 3 doses of CRM 197 –conjugate Haemophilus influenzae type b vaccine (study vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Hib TT
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Reporting group description |
Subjects treated with 3 doses of Tetanus Toxoid-conjugate Haemophilus influenzae type b vaccine (comparator vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Hib CRM197
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Reporting group description |
Subjects treated with 3 doses of CRM 197 –conjugate Haemophilus influenzae type b vaccine (study vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | ||
Reporting group title |
Hib TT
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Reporting group description |
Subjects treated with 3 doses of Tetanus Toxoid-conjugate Haemophilus influenzae type b vaccine (comparator vaccine): 2 doses given one month apart during study V37_07 (2014-005136-33) and a booster dose of the same vaccine six month after, during study V37_07E1 (2014-005135-13). No vaccine was administered during this trial | ||
Subject analysis set title |
Enrolled Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All screened subjects for which the parent or legal guardian provided the informed consent and provided demographic and/or other baseline screening assessments assigned a study subject ID.
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Subject analysis set title |
Per Protocol (PP) Set Immunogenicity
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects in the All Enrolled Set with no reportable protocol deviations
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End point title |
Geometric Mean Anti-PRP Concentrations at Day 1(approximately 4 years post booster dose administered in study V37_07E1) | |||||||||||||||
End point description |
Immunogenicity was measured as geometric mean of Anti- Polyribosyl Ribitol Phosphate (PRP) concentrations, approximately 4 years after booster vaccination with either Hib-CRM197 or Hib-TT in children participating in previous V37_07E1 trial (2014-005135-13).
Analysis was evaluated on the PPS (i.e. All subjects in the All Enrolled Set with no reportable protocol deviations).
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End point type |
Primary
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End point timeframe |
At Day 1 (approximately 4 years post booster dose administered in study V37_07E1).
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Statistical analysis title |
Ratios of Geometric Mean Anti-PRP Concentrations | |||||||||||||||
Comparison groups |
Hib CRM197 v Hib TT
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Number of subjects included in analysis |
426
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||
Method |
ANOVA | |||||||||||||||
Parameter type |
Vaccine Group Ratios | |||||||||||||||
Point estimate |
0.53
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.36 | |||||||||||||||
upper limit |
0.76 | |||||||||||||||
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End point title |
Percentages of Subjects with Anti-PRP Concentrations ≥1.0 μg/mL and ≥0.15 μg/mL at Day 1 (approximately 4 years post booster dose administered in study V37_07E1) | ||||||||||||||||||
End point description |
Immunogenicity was measured as the percentages of subjects with Anti- PRP concentrations ≥1.0 μg/mL and ≥0.15 μg/mL approximately 4 years after booster vaccination with either Hib-CRM197 or Hib-TT in V37_07E1 trial (2014-005135-13).
Analysis was evaluated on the PPS (i.e. All subjects in the All Enrolled Set with no reportable protocol deviations).
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End point type |
Secondary
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End point timeframe |
At Day 1 (approximately 4 years post booster dose administered in study V37_07E1)
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Statistical analysis title |
Anti-PRP Concentrations ≥1.0 μg/mL | ||||||||||||||||||
Comparison groups |
Hib CRM197 v Hib TT
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Number of subjects included in analysis |
426
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
Method |
Clopper-Pearson | ||||||||||||||||||
Parameter type |
Vaccine Group Differences | ||||||||||||||||||
Point estimate |
-11
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-18.6 | ||||||||||||||||||
upper limit |
-4.2 | ||||||||||||||||||
Statistical analysis title |
Anti-PRP Concentrations ≥0.15 μg/mL | ||||||||||||||||||
Comparison groups |
Hib CRM197 v Hib TT
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Number of subjects included in analysis |
426
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
Method |
Clopper-Pearson | ||||||||||||||||||
Parameter type |
Vaccine Group Differences | ||||||||||||||||||
Point estimate |
-11
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-18.6 | ||||||||||||||||||
upper limit |
-4.2 | ||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
NA
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Adverse event reporting additional description |
Safety was not accessed for this study.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
NA | ||
Dictionary version |
NA
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Safety was not assessed for this study. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
