Clinical Trial Results:
Safety and Immunogenicity of Sanofi Pasteur's Diphtheria, Tetanus, and Acellular Pertussis (DTaP)-Inactivated Poliovirus (IPV)-Hepatitis B (HB)-polyribosyl ribitol phosphate conjugated to tetanus protein (PRP-T) combined vaccine (DTaP-IPV-HB-PRP-T) Given as a Primary Series of Vaccination in Infants
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Summary
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EudraCT number |
2013-003267-55 |
Trial protocol |
PL |
Global end of trial date |
29 Aug 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Sep 2017
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First version publication date |
16 Sep 2017
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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 |
A3L45
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1143-8252 | ||
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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 |
Global Medical Affairs, Sanofi Pasteur SA, 33 (0)4 37 37 7464, olga.lyabis@sanofi.com
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Scientific contact |
Global Medical Affairs, Sanofi Pasteur SA, 33 (0)4 37 37 74 64, olga.lyabis@sanofi.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 |
31 Jan 2017
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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 Aug 2016
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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 |
Russian Federation: To describe the safety and reactogenicity of the study vaccine after a single dose in infants 6 months of age who had previously received 2 vaccinations of Pentaxim and 2 doses of HB vaccine and to evaluate the immunogenicity of the study vaccine 1 month after vaccination
Poland: To describe the safety and reactogenicity after each and all doses of the study vaccine administered as a 3-dose primary series
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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 |
27 Aug 2015
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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 |
Poland: 50
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Country: Number of subjects enrolled |
Russian Federation: 100
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Worldwide total number of subjects |
150
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EEA total number of subjects |
50
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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) |
150
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Children (2-11 years) |
0
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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 |
Study subjects were enrolled from 27 August 2015 to 09 February 2016 (Russia) and 12 January 2016 to 13 April 2016 (Poland) at 5 clinic centers in the Russian Federation and 2 clinic centers in Poland. | |||||||||
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Pre-assignment
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Screening details |
A total of 150 subjects who met all inclusion criteria and no exclusion criteria were enrolled and vaccinated. | |||||||||
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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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DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation) | |||||||||
Arm description |
Infants received a single dose of DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
DTaP-IPV-HB-PRP~T combined vaccine
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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 into the upper outer surface in the middle of the thigh, single dose (Russian Federation).
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Arm title
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DTaP-IPV-HB-PRP~T combined vaccine (Poland) | |||||||||
Arm description |
Infants received a 3-dose primary vaccination series of DTaP-IPV-HB-PRP~T (Poland) at Day 0, Day 45, and Day 90. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
DTaP-IPV-HB-PRP~T combined vaccine
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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 into the upper outer surface in the middle of the thigh, 1 dose each at Day 0, Day 45, and Day 90 (Poland)
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Baseline characteristics reporting groups
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Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation)
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Reporting group description |
Infants received a single dose of DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Poland)
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Reporting group description |
Infants received a 3-dose primary vaccination series of DTaP-IPV-HB-PRP~T (Poland) at Day 0, Day 45, and Day 90. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation)
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Reporting group description |
Infants received a single dose of DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation). | ||
Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Poland)
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Reporting group description |
Infants received a 3-dose primary vaccination series of DTaP-IPV-HB-PRP~T (Poland) at Day 0, Day 45, and Day 90. | ||
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End point title |
Percentage of Subjects Reporting Solicited Injection-site or Systemic Reactions After Vaccination with a Single Dose of Hexavalent DTaP-IPV-HB-PRP-T Combined Vaccine in Russian Federation [1] [2] | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Pyrexia, Vomiting, Crying, Somnolence, Decreased appetite, Irritability. Grade 3 Injection site reactions: Pain, Cries when injected limb is moved, or the movement of the limb is reduced; Erythema and Swelling, ≥50 mm. Grade 3 Systemic reactions: Pyrexia, >39.5°C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Somnolence, Sleeping most of the time or difficult to wake up; Decreased appetite, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable.
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 7 post-vaccination (Russian Federation)
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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 group and study vaccine administered for this outcome. [2] - 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: Only solicited injection-site and systemic reactions that occurred after a single dose of the combined vaccine (Russian Federation) are reported 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 or Systemic Reactions After Any and Each Dose of a Three-Dose Primary Series of Hexavalent DTaP-IPV-HB-PRP-T Combined Vaccine in Poland [3] [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Pyrexia, Vomiting, Crying, Somnolence, Decreased appetite, Irritability. Grade 3 Injection site reactions: Pain, Cries when injected limb is moved, or the movement of the limb is reduced; Erythema and Swelling, ≥50 mm. Grade 3 Systemic reactions: Pyrexia, >39.5°C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Somnolence, Sleeping most of the time or difficult to wake up; Decreased appetite, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable.
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 7 post-any and each vaccination
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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 group and study vaccine administered for this outcome. [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: Only solicited injection-site and systemic reactions that occurred after a three-dose primary series of the combined vaccine (Poland) are reported for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Seroprotection After Vaccination with a Single Dose of Hexavalent DTaP-IPV-HB-PRP-T Combined Vaccine in Russian Federation [5] | ||||||||||||||||||||||||||||||||||
End point description |
Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus was assessed using an enzyme-linked immunosorbent assay. Anti-Haemophilus influenza type b (Hib) capsular PRP antibodies were assessed by a Farr-type radioimmunoassay. Anti-Hepatitis B was measured using the commercially available VITROS ECi/ECIQ Immunodiagnostic System using chemiluminescence. Anti-Poliovirus (Polio) types 1, 2, and 3 antibodies were assessed by a neutralization assay. Seroprotection was defined as the following: Anti-Diphtheria ≥0.01 International Units (IU)/mL, ≥0.1 IU/mL, and ≥1.0 IU/mL; Anti-Tetanus ≥0.01 IU/mL, ≥0.1 IU/mL, ≥1.0 IU/mL; Anti-PRP ≥0.15 µg/mL and ≥1.0 µg/mL; Anti-Polio types 1, 2, and 3 ≥8 (1/dilution), Anti-Hepatitis B ≥10 mIU/mL and ≥100 mIU/mL.
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End point type |
Secondary
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End point timeframe |
1 month post-dose 1
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| Notes [5] - 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: Immunogenicity data are only available in infants who received a single dose of the combined vaccine (Russian Federation). |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Geometric Mean Concentrations (GMCs) of Antibodies Against Vaccine Antigens After Vaccination with a Single Dose of Hexavalent DTaP-IPV-HB-PRP-T Combined Vaccine in Russian Federation [6] | ||||||||||||||||||||||||||
End point description |
Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus, Anti-Pertussis toxoid, and Anti-Filamentous hemagglutinin (FHA) antibodies were assessed using an enzyme-linked immunosorbent assay. Anti-Hib capsular PRP antibodies were assessed by a Farr-type radioimmunoassay. Anti-Hepatitis B was measured using the commercially available VITROS ECi/ECIQ Immunodiagnostic System using chemiluminescence. Anti-Polio types 1, 2, and 3 antibodies were assessed by a neutralization assay.
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End point type |
Secondary
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End point timeframe |
1 month post-dose 1
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| Notes [6] - 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: Immunogenicity data are only available in infants who received a single dose of the combined vaccine (Russian Federation). |
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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 30 post-dose 3.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
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Reporting groups
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Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation)
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Reporting group description |
Infants received a single dose of DTaP-IPV-HB-PRP~T combined vaccine (Russian Federation). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DTaP-IPV-HB-PRP~T combined vaccine (Poland)
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Reporting group description |
Infants received a 3-dose primary vaccination series of DTaP-IPV-HB-PRP~T (Poland) at Day 0, Day 45, and Day 90. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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23 Mar 2015 |
Clarified the age of infants to be included in the study from 6 months to 6 months and 29 days, excluded infants under 6 months of age, included a recommendation to start the study in a limited group of subjects; if satisfactory results were observed (absence of SAEs), then the study would continue, and revised the wording describing the site of injection from "anterolateral thigh" to "upper outer part of the middle thigh" to be consistent with local Russian guidelines. |
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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 | |||
