Clinical Trial Results:
A Phase IV, Multicenter, Randomized, Observer-blind, Parallel-arm Study to Evaluate the Safety and Tolerability of CSL’s Trivalent Influenza Virus Vaccine (CSL TIV) in Children 5 to Less Than 9 Years of Age.
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Summary
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EudraCT number |
2015-000175-27 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jun 2016
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First version publication date |
12 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 |
CSLCT-USF-10-69
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02212106 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
bioCSL PTY LTD
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Sponsor organisation address |
63 Poplar Rd, Parkville, Australia, 3052
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Public contact |
Clinical Program Director, bioCSL PTY LTD, bioCSL.ClinicalTrials@biocsl.com.au
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Scientific contact |
Clinical Program Director, bioCSL PTY LTD, bioCSL.ClinicalTrials@biocsl.com.au
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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 |
26 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Dec 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 evaluate the frequency and intensity of fever in healthy pediatric subjects 5 to less than 9 years of age administered the 2014-2015 Northern Hemisphere season formulation of bioCSL TIV, in the 7 days after each administration.
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Protection of trial subjects |
The Sponsor or its agents submitted the appropriate documents to the local regulatory agencies and IRBs for approval before study start. The principles of informed consent in the Declaration of Helsinki were implemented in this clinical study before protocol specified procedures were carried out. This Phase IV study was conducted as a post marketing study under a United States (US) Investigational New Drug (IND) application and documented in accordance with US guidelines and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United States: 402
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Worldwide total number of subjects |
402
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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) |
402
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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 |
First Patient In: 22-SEP-2014 Last Patient In: 15-OCT-2014 Last Patient Last Visit: 05-DEC-2014 Number of activated sites: 11 (all based in USA). | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Number of subjects screened: 407 Number of screen failures: 5 (Reason: all due to not meeting inclusion/exclusion criteria). | ||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Subject, Data analyst, Carer, Assessor | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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bioCSL Trivalent Influenza Virus Vaccine (bioCSL TIV) | ||||||||||||||||||||||||
Arm description |
The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
bioCSL Trivalent Influenza Virus Vaccine (bioCSL TIV)
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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 |
The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season).
Subjects received one or two study vaccinations depending on their influenza vaccine history. The vaccine was administered by intramuscular injection.
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Arm title
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Comparator Quadrivalent Influenza Virus Vaccine | ||||||||||||||||||||||||
Arm description |
The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Comparator Quadrivalent Influenza Virus Vaccine
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Investigational medicinal product code |
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Other name |
Fluzone® Quadrivalent
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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 |
The comparator vaccine was supplied in a thimerosal free, prefilled syringe containing 60 mcg HA in 0.5 mL (15 mcg of each of the four strains) for each vaccination.
The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season.
Subjects received one or two study vaccinations depending on their influenza vaccine history. The vaccine will be administered by intramuscular injection.
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Baseline characteristics reporting groups
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Reporting group title |
bioCSL Trivalent Influenza Virus Vaccine (bioCSL TIV)
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Reporting group description |
The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparator Quadrivalent Influenza Virus Vaccine
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Reporting group description |
The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season. | ||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
bioCSL TIV
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized subjects who received at least one scheduled vaccination and had postvaccination follow-up safety data available.
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Subject analysis set title |
Comparator QIV
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized subjects who received at least one scheduled vaccination and had postvaccination follow-up safety data available.
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End points reporting groups
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Reporting group title |
bioCSL Trivalent Influenza Virus Vaccine (bioCSL TIV)
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Reporting group description |
The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). | ||
Reporting group title |
Comparator Quadrivalent Influenza Virus Vaccine
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Reporting group description |
The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season. | ||
Subject analysis set title |
bioCSL TIV
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All randomized subjects who received at least one scheduled vaccination and had postvaccination follow-up safety data available.
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Subject analysis set title |
Comparator QIV
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All randomized subjects who received at least one scheduled vaccination and had postvaccination follow-up safety data available.
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End point title |
The frequency and intensity of fever events occurring during the 7 days after each administration of bioCSL TIV vaccine. [1] | ||||||||||||||
End point description |
The overall number of subjects reporting at least one fever event after administration of bioCSL TIV.
A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows:
• Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C)
• Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C)
• Severe: ≥ 102.2°F (≥ 39.0°C)
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End point type |
Primary
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End point timeframe |
7 days after each administration of vaccine.
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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: Data were analysed using descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
The frequency and intensity of fever events occurring during the 7 days after each administration of bioCSL TIV vaccine. [2] | ||||||||||||||||
End point description |
The overall percentage of subjects reporting at least one fever event after administration of bioCSL TIV.
A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows:
• Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C)
• Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C)
• Severe: ≥ 102.2°F (≥ 39.0°C)
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End point type |
Primary
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End point timeframe |
7 days after each administration of vaccine.
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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: Data were analysed using descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
The frequency and intensity of fever events occurring during the 7 days after each administration of the comparator influenza virus vaccine. | ||||||||||||||
End point description |
The overall number of subjects reporting at least one fever event after administration of the comparator influenza virus vaccine.
A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows:
• Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C)
• Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C)
• Severe: ≥ 102.2°F (≥ 39.0°C)
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccine.
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
The frequency and intensity of fever events occurring during the 7 days after each administration of the comparator influenza virus vaccine. | ||||||||||||||||
End point description |
The overall percentage of subjects reporting at least one fever event after administration of the comparator influenza virus vaccine.
A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows:
• Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C)
• Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C)
• Severe: ≥ 102.2°F (≥ 39.0°C)
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccine.
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
The frequency and intensity of vaccine-related fever events occurring during the 7 days after each administration of bioCSL TIV vaccine or comparator influenza virus vaccine. | ||||||||||||||||||||||||
End point description |
Proportion of subjects with a related fever event (overall) by study vaccine group based on the number of subjects contributing any follow up safety information for at least one data value of an individual sign/symptom. Excludes subjects with missing intensity information for the whole 7 days.
Mild fever: ≥ 100.4 to < 101.3º F (≥ 38.0 to < 38.5º C).
Moderate fever: ≥ 101.3 to < 102.2º F (≥ 38.5 to < 39.0º C).
Severe fever: ≥ 102.2º F (≥ 39.0º C).
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccine.
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
The frequency and intensity of solicited local Adverse Events (AEs). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The overall frequency and intensity of solicited local Adverse Events (AEs) occurring during the 7 days after each administration of bioCSL TIV or the comparator influenza virus vaccine.
Proportion of subjects who experienced each event are based on the number of subjects in the Safety Population group. Excludes subjects with missing intensity information for the whole 7 days.
Percentages for intensity are based on the number of subjects with non-missing intensity data. Only the maximum intensity experienced between Day 1 and Day 7 are presented for each subject.
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccine.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
The frequency and intensity of solicited systemic Adverse Events (AEs). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The overall frequency and intensity of solicited systemic Adverse Events (AEs) occurring during the 7 days after each administration of CSL TIV or the comparator influenza virus vaccine.
Proportion of subjects who experienced each event are based on the number of subjects in the Safety
Population group. Excludes subjects with missing intensity information for the whole 7 days.
Percentages for intensity are based on the number of subjects with non-missing intensity data. Only the
maximum intensity experienced between Day 1 and Day 7 are presented for each subject.
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccination.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
The frequency and intensity of unsolicited Adverse Events (AEs). | ||||||||||||||||||||||||
End point description |
The overall frequency and intensity of unsolicited Adverse Events (AEs) occurring during the 7 days after
each administration of CSL TIV or the comparator influenza virus vaccine.
Proportion of subjects who experienced each event are based on the number of subjects in the Safety
Population group. Excludes subjects with missing intensity information for the whole 7 days.
If a subject has multiple events of the same intensity or causality, then they are counted only once in that intensity or causality. However, subjects can be counted more than once overall.
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End point type |
Secondary
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End point timeframe |
7 days after each administration of vaccine.
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
The incidence of Serious Adverse Events (SAEs). | |||||||||
End point description |
The number of subjects experiencing at least 1 SAE.
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End point type |
Secondary
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End point timeframe |
7 days after each vaccination.
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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 |
7 days after each vaccination.
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Adverse event reporting additional description |
Overall data (following first & second vaccination) for Safety Population is shown.
If a subject has multiple events of the same intensity or causality, then they are counted only once in that intensity or causality. However, subjects can be counted more than once overall
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
bioCSL Trivalent Influenza Virus Vaccine (bioCSL TIV)
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Reporting group description |
The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). Subjects received one or two study vaccinations depending on their influenza vaccine history. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparator Quadrivalent Influenza Virus Vaccine
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Reporting group description |
The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season. Subjects received one or two study vaccinations depending on their influenza vaccine history. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Feb 2014 |
Protocol amendment 1 Final Version 2.0, included the following changes:
• Update the tertiary objective/endpoints to secondary objectives/endpoints (safety and tolerability after vaccination with test and comparator vaccines).
• Clarified that if multiple temperatures readings are taken, the maximum reading for each day should be recorded.
• Added prophylactic antipyretics on the day of vaccination to prohibited medicines section. |
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02 May 2014 |
Protocol amendment 2 Final Version 3.0, included the following changes:
• Change in terminology of comparator group from Comparator Influenza Virus Vaccine to Comparator Trivalent Influenza Virus Vaccine (TIV)
• Change in the enrollment halting rules
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05 Aug 2014 |
Protocol amendment 3 Final Version 4.0, included the following changes:
• Addition of PI and Sponsor details, number of treatments, text in dosage and administration section. |
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04 Sep 2014 |
Protocol amendment 4 Final Version 5.0, included the following changes:
• Corrections and additions of text from Comparator TIV to Comparator QIV.
All subjects enrolled to the trial were enrolled under this amendment (version 5).
Note: The sponsor, bioCSL, was previously known as CSL Biotherapies. It should therefore be noted that, in the study documents (including the protocol and statistical analysis plan) bioCSL TIV is referred to as CSL TIV. |
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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 | |||
