Clinical Trial Results:
A Randomized, Double-blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children
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Summary
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EudraCT number |
2009-013326-17 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
27 Dec 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jan 2016
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First version publication date |
31 Jan 2016
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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 |
MI-CP208
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01091246 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
MedImmune, LLC
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Sponsor organisation address |
One MedImmune Way, Gaithersburg, United States, MD 20878
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Public contact |
Clinical Trial Enquiries, MedImmune, LLC, clinicaltrialenquiries@medimmune.com
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Scientific contact |
Raburn Mallory, Sr Director Clinical Development, MedImmune, LLC, RaburnM@MedImmune.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001051-PIP01-10 | ||
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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Dec 2010
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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 |
27 Dec 2010
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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 primary objective of this study was to demonstrate the immunologic non-inferiority of quadrivalent live, attenuated influenza vaccine (MEDI3250) (Q/LAIV) to FluMist in children 2 to 17 years of age by comparing the post dose strain specific geometric mean titers (GMT) of serum hemagglutination inhibition (HAI) antibody.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Mar 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Months | ||
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: 2312
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Worldwide total number of subjects |
2312
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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) |
1993
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Adolescents (12-17 years) |
319
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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 |
A total of 2,481 participants provided written informed consent and were screened for the study. Of these, 2,312 participants were randomized into the study between 29Mar2010 to 12May2010 at 97 sites in the USA. | ||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Eligible participants were randomized in a 3:1:1 ratio to receive Q/LAIV, FluMist/B/Yamagata, or FluMist/B/Victoria. Randomization was stratified by age (2 to 8 years, 9 to 17 years). For subjects 2 to 8 years of age only, randomization was also stratified by previous seasonal influenza vaccination history. | ||||||||||||||||||||||||||||||||
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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 |
Double blind | ||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, 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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Q/LAIV (MEDI3250) | ||||||||||||||||||||||||||||||||
Arm description |
Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]). | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MEDI3250
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, suspension
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Routes of administration |
Nasal use
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Dosage and administration details |
Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).
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Arm title
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FluMist/B/Yamagata | ||||||||||||||||||||||||||||||||
Arm description |
FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]). | ||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
FluMist-Y
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, suspension
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Routes of administration |
Nasal use
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Dosage and administration details |
FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]).
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Arm title
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FluMist/B/Victoria | ||||||||||||||||||||||||||||||||
Arm description |
FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]). | ||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
FluMist-V
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, suspension
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Routes of administration |
Nasal use
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Dosage and administration details |
FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]).
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Baseline characteristics reporting groups
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Reporting group title |
Q/LAIV (MEDI3250)
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Reporting group description |
Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FluMist/B/Yamagata
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Reporting group description |
FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FluMist/B/Victoria
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Reporting group description |
FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Q/LAIV (MEDI3250)
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Reporting group description |
Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]). | ||
Reporting group title |
FluMist/B/Yamagata
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Reporting group description |
FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]). | ||
Reporting group title |
FluMist/B/Victoria
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Reporting group description |
FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]). | ||
Subject analysis set title |
All FluMist Group: Immunogenicity Population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The Immunogenicity Population included all participants who received any investigational product and had post dose HAI antibody measurement and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
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Subject analysis set title |
All FluMist Group: A/H1N1
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=878).
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Subject analysis set title |
All FluMist Group: A/H3N2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=879).
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Subject analysis set title |
All FluMist Group: Serosusceptible to A/H1N1
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).
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Subject analysis set title |
All FluMist Group: Serosusceptible to A/H3N2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).
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Subject analysis set title |
All FluMist Group: Seronegative to A/H1N1
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=460; All FM=321).
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Subject analysis set title |
All FluMist Group: Seronegative to A/H3N2
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=364; All FM=244).
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Subject analysis set title |
Post Dose 1 solicited symptoms analyses
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The total number of subjects evaluable for post Dose 1 solicited symptoms analyses (SSA) were reported.
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Subject analysis set title |
Post-dose 1 solicited symptoms analyses: 2-dose group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The number of subjects evaluable for post Dose 1 solicited symptoms analyses for two-dose group were reported.
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Subject analysis set title |
Post Dose 2 solicited symptoms analyses
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The total number of subjects evaluable for post Dose 2 solicited symptoms analyses were reported.
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Subject analysis set title |
All FluMist Group: Safety population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The Safety Population included all participants who received any investigational product and had safety data available. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
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Subject analysis set title |
Safety population: Two-dose group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who received a different investigational product at Dose 2 than at Dose 1 were excluded from the Safety Population for Dose 2. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
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Subject analysis set title |
Evaluable Safety population: Two-dose group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who received a different investigational product at Dose 2 than at Dose 1 were excluded from the Safety Population for Dose 2. Evaluable subjects of the two-doe group were reported. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.
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End point title |
The 4 post-dose strain-specific serum hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) in the Q/LAIV (MEDI3250) arm are noninferior to those in the comparator FluMist group. | ||||||||||||||||||||||||||||||||||||||||
End point description |
Non-inferior immune response was defined as having the upper bound of the 2-sided 95% confidence intervals (CIs) for the HAI antibody GMT ratio (FluMist comparator divided by Q/LAIV) ≤ 1.5 for each of the 4 strains. In the below table, '99999' indicates data was not reported since, the comparators for the GMT ratios for the primary endpoint were participants in the All FluMist group (combined data for both FluMist arms) for A/H1N1 and A/H3N2 strains. '88888' indicates data was not reported since B/Yamagata strain not in the investigational product. '77777' indicates data was not reported since B/Victoria strain not in the investigational product. All participants who received any investigational product (Q=1385; FY=464; FV=463; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FY=445; FV=437; All FM=883).
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End point type |
Primary
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End point timeframe |
Day 28 post immunogenicity dose
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
A/H1N1: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata + FluMist/B/Victoria) / (Q/LAIV) for A/H1N1 strain
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Comparison groups |
Q/LAIV (MEDI3250) v All FluMist Group: Immunogenicity Population
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Number of subjects included in analysis |
2210
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||||||||||||||||||||||||||||||
Method |
Bootstrapping | ||||||||||||||||||||||||||||||||||||||||
Parameter type |
Ratio of geometric mean | ||||||||||||||||||||||||||||||||||||||||
Point estimate |
1.07
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.98 | ||||||||||||||||||||||||||||||||||||||||
upper limit |
1.16 | ||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. |
|||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | ||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
A/H3N2: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata + FluMist/B/Victoria) / (Q/LAIV) for A/H3N2 strain
|
||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Q/LAIV (MEDI3250) v All FluMist Group: Immunogenicity Population
|
||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
2210
|
||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [2] | ||||||||||||||||||||||||||||||||||||||||
Method |
Bootstrapping | ||||||||||||||||||||||||||||||||||||||||
Parameter type |
Ratio of geometric means | ||||||||||||||||||||||||||||||||||||||||
Point estimate |
1.04
|
||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||
lower limit |
0.94 | ||||||||||||||||||||||||||||||||||||||||
upper limit |
1.14 | ||||||||||||||||||||||||||||||||||||||||
| Notes [2] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% CIs were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared. |
|||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 3 | ||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
B/Yamagata: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata) / (Q/LAIV) for B/Yamagata strain
|
||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Q/LAIV (MEDI3250) v FluMist/B/Yamagata
|
||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1772
|
||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [3] | ||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||
Parameter type |
Ratio of geometric mean | ||||||||||||||||||||||||||||||||||||||||
Point estimate |
1.21
|
||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||
lower limit |
1.07 | ||||||||||||||||||||||||||||||||||||||||
upper limit |
1.37 | ||||||||||||||||||||||||||||||||||||||||
| Notes [3] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% CIs were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared. |
|||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 4 | ||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
B/Victoria: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Victoria) / (Q/LAIV) for B/Victoria strain
|
||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Q/LAIV (MEDI3250) v FluMist/B/Victoria
|
||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1764
|
||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [4] | ||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||
Parameter type |
Ratio of geometric mean | ||||||||||||||||||||||||||||||||||||||||
Point estimate |
1.05
|
||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||
lower limit |
0.93 | ||||||||||||||||||||||||||||||||||||||||
upper limit |
1.18 | ||||||||||||||||||||||||||||||||||||||||
| Notes [4] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% confidence intervals were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared. |
|||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
The Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [5] | ||||||||||||
End point description |
Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=878).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [6] | ||||||||||||
End point description |
Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; All FM=879).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [7] | ||||||||||||
End point description |
Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline.
All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; FY=441).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [7] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [8] | ||||||||||||
End point description |
Seroresponse was defined as a ≥ 4-fold rise from baseline.
All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; FV=437).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [8] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [9] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [9] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [10] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [10] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [11] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=588; FY=192).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [11] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [12] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=620; FV=191).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [12] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [13] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=460; All FM=321).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [13] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [14] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=364; All FM=244).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [14] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [15] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=483; FY=165).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [15] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [16] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline.
All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=487; FV=159).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 and Day 28 post immunogenicity dose
|
||||||||||||
| Notes [16] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Who Achieved an A/H1N1 or A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [17] | ||||||||||||||||||
End point description |
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; All FM=883).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||||||||
| Notes [17] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [18] | ||||||||||||
End point description |
All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FY=445).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [18] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Participants (Regardless of Serostatus) Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [19] | ||||||||||||
End point description |
All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FV=437).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [19] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [20] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [20] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [21] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [21] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [22] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [22] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Serosusceptible Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [23] | ||||||||||||
End point description |
Serosusceptible was defined as a baseline HAI titer ≤ 8. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=588; FY=192).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [23] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [24] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=620; FV=191).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [24] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [25] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=460; All FM=321).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [25] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [26] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4.
All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=364; All FM=244).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [26] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Seronegative Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [27] | ||||||||||||
End point description |
Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=487; FV=159).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 28 post immunogenicity dose
|
||||||||||||
| Notes [27] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent of All Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 [28] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. All participants who received any investigational product (Q=1385; All FM=927) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1377; All FM=920).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 0-14 Post Dose 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [28] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 [29] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom.
All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1078; All FM=716).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 0-14 Post Dose 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [29] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Dose 2 During Days 0-14 Post Dose 2 [30] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom.
All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1039; All FM=692).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 0-14 Post Dose 2
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [30] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percent of All Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 [31] | ||||||||||||
End point description |
Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-28 Post Dose 1
|
||||||||||||
| Notes [31] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 [32] | ||||||||||||
End point description |
Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any safety data were recorded during the summarized period (Q=1083; All FM=719).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-28 Post Dose 1
|
||||||||||||
| Notes [32] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Dose 2 Through 28 Days Post Dose 2 [33] | ||||||||||||
End point description |
Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any post Dose 2 safety data were recorded during the summariezed period (Q=1041; All FM=693).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-28 Post Dose 2
|
||||||||||||
| Notes [33] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of All Participants Reporting Any Serious Adverse Event (SAE) From Administration of Investigational Product Through Day 28 Post Dose 1 [34] | ||||||||||||
End point description |
SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above.
All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-28 Post Dose 1
|
||||||||||||
| Notes [34] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of Two-dose Participants Reporting Any SAE From Administration of Dose 2 During Days 0-28 Post Dose 2 [35] | ||||||||||||
End point description |
SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above.
All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any post Dose 2 safety data were recorded during the summarized period (Q=1041; All FM=693).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-28 Post Dose 2
|
||||||||||||
| Notes [35] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of All Participants Reporting Any SAE From Administration of Investigational Product Through 180 Days Post Last Dose [36] | ||||||||||||
End point description |
SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-180 Post Last Dose
|
||||||||||||
| Notes [36] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percent of All Participants Reporting Any New Onset Chronic Disease (NOCD) From Administration of Investigational Product Through 180 Days Post Last Dose [37] | ||||||||||||
End point description |
An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant.
All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 0-180 Post Last Dose
|
||||||||||||
| Notes [37] - 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: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were collected from Day 0 through 28 after Doses 1 and 2. Serious adverse events were collected between Days 0-180 after the last dose administered.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
|
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|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All FluMist Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Q/LAIV (MEDI3250)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Sep 2009 |
Major changes to the study design incorporated in Amendment 1 were: 1) Entire protocol: Remove the blow-fill-seal (BFS) arm; QLAIV was only provided in the BD Accuspray device. This resulted in a change in number of subjects enrolled. The inclusion of the BFS arm did not permit complete blinding of the investigational product due to the differences between the Accuspray and BFS devices. Because the BFS arm was removed, the study was now completely blinded. The protocol title was therefore changed from “A Randomized, Partially Blinded, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children” to its current title of “A Randomized, Double-Blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children” 2) Section 7.3.1 (Primary Endpoint): Amended the statistical analysis section so that the primary endpoint was met if the upper bound of the two-sided 95% CIs for the strainspecific HAI antibody GMT ratios (FluMist divided by Q/LAIV) was ≤ 2 for all 4 strains. 3) Section 7.3.2 (Secondary Endpoints): Amended the definition of seronegative and serosusceptible to include HAI antibody values that were not whole numbers, because each time point was assayed in duplicate, and if the results were within one dilution, the GMT was calculated and used for analysis. Values that differed by more than one dilution for a single specimen were repeated. 4) Section 5.2 (Schedule of Study Procedures): Added a temperature log, which was to be collected. Clarified that a memory aid was supplied to subjects, but it was not considered to be source data and was not collected. 5) Section 1.4.1 (Safety of Q/LAIV in Study MI-CP185): Provided data from on-going Study MI-CP185, a study of Q/LAIV in adults. |
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09 Mar 2010 |
Major changes to the study incorporated in Amendment 2 were: 1) Added unblinded MI-CP185 safety and immunogenicity data. 2) Entire protocol: Clarified that the subject history of prior influenza vaccination that was used to stratify enrollment and to assign the timing of the immunogenicity blood sample was a history of prior seasonal influenza vaccination, because of the possibility that children might have received a prior influenza vaccine that consisted only of monovalent pandemic H1N1. 3) Entire protocol: Amended the noninferiority margin from 2.0 to 1.5 in accordance with guidance from the US FDA. 4) Abstract, Overview of Study Design and Treatment Assignment: Removed site as a stratification factor for randomization, 5) Exclusion Criteria: Modified the concomitant medications window around exclusion criteria numbers 4, 5, 7, 8, 12, 14 from 30 days to 28 days to be consistent with the concomitant medication reporting period and clarified that salicylate-containing medications were prohibited. 6) Exclusion Criteria: Added, “A history of epilepsy, seizure, or an evolving neurological condition except that a single febrile seizure that occurred 3 or more years prior to enrollment would not disqualify a subject” in accordance with guidance from the Canadian IRB. 7) Blinding: Clarified that all MedImmune staff were unblinded for the Day 28 safety and immunogenicity analyses, but site staff, CRO staff, and subjects were to remain blinded until the Day 180 final database lock 8) Concomitant Medications: Modified concomitant medications windows to be consistent with the concomitant medication reporting period and clarified that salicylate-containing medications were prohibited. 9) Clarified the relationship between severity Grading 1-5 and the wording mild, moderate, severe, life-threatening and fatal, because the EDC system contained these words. |
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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 | |||
