Clinical Trial Results:
A Phase IIIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza From Otherwise Healthy Patients to Household Contacts
Summary
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EudraCT number |
2018-004056-37 |
Trial protocol |
ES GB GR HU PL FR BG |
Global end of trial date |
10 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2024
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First version publication date |
15 Dec 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MV40618
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03969212 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Hoffmann-La Roche
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4058
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Aug 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 May 2024
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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 evaluate the efficacy of a single, oral dose of baloxavir marboxil (BXM) compared with a placebo to prevent secondary within-household transmission of influenza A/B.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Oct 2019
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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 |
Greece: 7
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Country: Number of subjects enrolled |
Hungary: 24
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Country: Number of subjects enrolled |
Israel: 148
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Country: Number of subjects enrolled |
Poland: 85
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Country: Number of subjects enrolled |
Spain: 15
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Country: Number of subjects enrolled |
Türkiye: 230
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Country: Number of subjects enrolled |
United States: 1310
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Country: Number of subjects enrolled |
Bulgaria: 1041
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Country: Number of subjects enrolled |
Costa Rica: 6
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Country: Number of subjects enrolled |
Mexico: 44
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Country: Number of subjects enrolled |
South Africa: 112
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Country: Number of subjects enrolled |
China: 441
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Country: Number of subjects enrolled |
Japan: 668
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
India: 2
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Worldwide total number of subjects |
4134
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EEA total number of subjects |
1172
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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) |
433
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Adolescents (12-17 years) |
495
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Adults (18-64 years) |
3063
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From 65 to 84 years |
132
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85 years and over |
11
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Recruitment
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Recruitment details |
Participants with acute influenza infection (Index participants [IPs]) and their household contacts (HHCs) took part in the study across 142 investigative sites in 15 countries from 10 October 2019 to 10 May 2024. A total of 4138 participants, 1457 IPs, and 2681 HHCs, were included in the study. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
IPs received baloxavir marboxil or placebo in a 1:1 ratio, and their evaluable HHCs were assessed for influenza symptoms. No treatment was administered to the HHCs. Of the 1345 HHCs enrolled in ‘Baloxavir Marboxil:HHCs’, 1305 completed the study. Baseline data was not collected for 4 HHCs, hence only 1341 HHCs are presented in the disposition. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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, Monitor, Carer, Data analyst, Assessor | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo: IPs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
IPs were randomized in this arm to receive a single dose of matching placebo orally as a tablet or oral suspension based on their weight and age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Granules for oral suspension, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Single, oral dose of matching placebo administered according to age and weight of IPs.
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Arm title
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Baloxavir Marboxil: IPs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
IPs were randomized in this arm to receive a single dose of baloxavir marboxil orally based on their weight and age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Baloxavir Marboxil
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Investigational medicinal product code |
RO7191686
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Other name |
XOFLUZA
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Pharmaceutical forms |
Granules for oral suspension, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Single, oral dose of baloxavir marboxil administered according to age and weight of IPs.
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Arm title
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Placebo: HHCs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
HHCs related to IPs randomized to the placebo arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Baloxavir Marboxil: HHCs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
HHCs related to IPs randomized to the baloxavir marboxil arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: HHCs were not treated in this study. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: HHCs were not treated in this study. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo: IPs
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Reporting group description |
IPs were randomized in this arm to receive a single dose of matching placebo orally as a tablet or oral suspension based on their weight and age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baloxavir Marboxil: IPs
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Reporting group description |
IPs were randomized in this arm to receive a single dose of baloxavir marboxil orally based on their weight and age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo: HHCs
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Reporting group description |
HHCs related to IPs randomized to the placebo arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baloxavir Marboxil: HHCs
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Reporting group description |
HHCs related to IPs randomized to the baloxavir marboxil arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo: IPs
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Reporting group description |
IPs were randomized in this arm to receive a single dose of matching placebo orally as a tablet or oral suspension based on their weight and age. | ||
Reporting group title |
Baloxavir Marboxil: IPs
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Reporting group description |
IPs were randomized in this arm to receive a single dose of baloxavir marboxil orally based on their weight and age. | ||
Reporting group title |
Placebo: HHCs
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Reporting group description |
HHCs related to IPs randomized to the placebo arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | ||
Reporting group title |
Baloxavir Marboxil: HHCs
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Reporting group description |
HHCs related to IPs randomized to the baloxavir marboxil arm were evaluated for influenza transmission (either virological or symptomatic) up to Day 9 of the observation period without any treatment being administered. | ||
Subject analysis set title |
Placebo: Household
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All households of randomized IPs who received matching placebo, with the IP being PCR positive at screening and with at least one HHC enrolled for the full study.
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Subject analysis set title |
Baloxavir Marboxil: Household
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All households of randomized IPs who received baloxavir marboxil, with the IP being PCR positive at screening and with at least one HHC enrolled for the full study.
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End point title |
Percentage of HHCs With Virological Influenza Transmission by Day 5 [1] | |||||||||||||||
End point description |
The virological transmission was determined based on Polymerase Chain Reaction Positive (PCR+) influenza test results. Percentage of HHCs who tested PCR+ for influenza by Day 5 post IP randomization with virus subtype matching with that of the respective IP, irrespective of being symptomatic or asymptomatic are reported. The primary household contacts analysis set (PAS-HC) included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) to Day 5
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Notes [1] - 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 planned to only evaluate the HHCs associated with the IPs. |
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Statistical analysis title |
Baloxavir Marboxil vs Placebo | |||||||||||||||
Statistical analysis description |
The odds ratio (OR) shown represents the odds of Baloxavir Marboxil (BMX) versus the odds of Placebo.
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Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
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Number of subjects included in analysis |
2216
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.013 | |||||||||||||||
Method |
Generalized estimating equation (GEE) | |||||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | |||||||||||||||
Point estimate |
0.68
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Confidence interval |
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level |
95.38% | |||||||||||||||
sides |
2-sided
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lower limit |
0.5 | |||||||||||||||
upper limit |
0.93 |
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End point title |
Percentage of HHCs With Symptomatic Influenza Transmission by Day 5 [2] | ||||||||||||
End point description |
Virological transmission was determined based on PCR+ influenza test results. Percentage of HHCs who were PCR+ for influenza by Day 5 post IP randomization with virus subtype matching with respective IP & develop symptoms at any time during the study are reported. HHCs ≥12 years old were symptomatic if 1. Presence of temperature ≥38.0 Celsius & 1 respiratory symptom or 2. Presence of one respiratory symptom & 1 general systemic symptom (headache, feverishness or chills, muscle or joint pain, fatigue), with /without a fever. HHCs ≥2 & <12 years old were symptomatic if the presence of temperature was ≥38.0 Celsius & upper respiratory tract infection signs or symptoms (cough, nasal congestion, or rhinorrhea). Symptoms must be either new, or have worsened versus baseline (BA) in HHC with BA symptoms due to a preexisting comorbidity. PAS-HC=unvaccinated HHCs who were linked to HHs where IP was BA PCR+ for influenza A/B, received study drug, & where all contacts were PCR negative at BA.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 5
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was planned to only evaluate the HHCs associated with the IPs. |
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Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
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Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
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Number of subjects included in analysis |
2216
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.155 | ||||||||||||
Method |
GEE model | ||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | ||||||||||||
Point estimate |
0.75
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Confidence interval |
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level |
95.38% | ||||||||||||
sides |
2-sided
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lower limit |
0.5 | ||||||||||||
upper limit |
1.12 |
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End point title |
Percentage of Households (HHs) With Virological Influenza Transmission at Household Level by Day 5 | ||||||||||||
End point description |
Percentage of households with at least one HHC who met the primary endpoint of virological transmission by Day 5 are reported. Primary Households Analysis Set (PAS-HH) included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the Primary Index Patients Analysis Set (PAS-IP) which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 5
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Notes [3] - Number analyzed represents the number of households analyzed for this endpoint. [4] - Number analyzed represents the number of households analyzed for this endpoint. |
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Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
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Comparison groups |
Placebo: Household v Baloxavir Marboxil: Household
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Number of subjects included in analysis |
1092
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Odds Ratio (BMX vs Placebo) | ||||||||||||
Point estimate |
0.76
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Confidence interval |
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level |
95.38% | ||||||||||||
sides |
2-sided
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lower limit |
0.55 | ||||||||||||
upper limit |
1.06 |
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End point title |
Percentage of Households With Symptomatic Influenza Transmission at Household Level by Day 5 | ||||||||||||
End point description |
Percentage of households with at least one HHC who meets the symptomatic transmission by Day 5 endpoint are reported. PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 5
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Notes [5] - Number analyzed represents the number of households analyzed for this endpoint. [6] - Number analyzed represents the number of households analyzed for this endpoint. |
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Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
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Comparison groups |
Placebo: Household v Baloxavir Marboxil: Household
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Number of subjects included in analysis |
1092
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Odds Ratio (BMX vs Placebo) | ||||||||||||
Point estimate |
0.69
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Confidence interval |
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level |
95.38% | ||||||||||||
sides |
2-sided
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lower limit |
0.46 | ||||||||||||
upper limit |
1.04 |
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End point title |
Percentage of HHCs With Virological Influenza Transmission by Day 9 [7] | ||||||||||||
End point description |
Virological transmission was determined based on PCR+ influenza test results. Data are reported for percentage of HHCs who tested PCR+ for influenza by Day 9 post IP randomization with virus subtype matching with the respective IP, irrespective of being symptomatic/asymptomatic including: 1. all HHC meeting primary endpoint, AND 2. all HHC cases detected after Day 5 meeting following criteria: 2a. included HHC case was in an HH where another HHC had already met the primary endpoint OR 2b. included HHC case was PCR+ bearing an amino acid substitution of isoleucine for another amino acid at position 38 (I38X) in the polymerase acidic (PA) protein (PA/I38X substitution) or amino acid substitution of threonine to lysine at position 20 in the PA protein for influenza B only (PA/T20K), indicating transmission of virus with reduced susceptibility. PAS-HC analysis set used for this endpoint. Overall number analyzed=number of HHCs with data available for analysis.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 9
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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 planned to only evaluate the HHCs associated with the IPs. |
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Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
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Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
|
||||||||||||
Number of subjects included in analysis |
2119
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | ||||||||||||
Point estimate |
0.66
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.48 | ||||||||||||
upper limit |
0.91 |
|
|||||||||||||
End point title |
Percentage of HHCs With Symptomatic Influenza Transmission by Day 9 [8] | ||||||||||||
End point description |
Data are reported for the percentage of HHCs who met the virological transmission by Day 9 endpoint and developed symptoms at any time during the study. HHCs ≥12 years were symptomatic if they had 1. temperature ≥38.0°C & one respiratory symptom or 2. one respiratory and one systemic symptom, with/without fever. HHCs ≥2 & <12 years were symptomatic if with a temperature ≥38.0°C and upper respiratory symptoms. Symptoms must be either new, or have worsened versus baseline in HHC with baseline symptoms due to a preexisting comorbidity. PAS-HC included unvaccinated HHCs who were linked to households where IP was baseline PCR+ for influenza A or B, received study drug, and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) to Day 9
|
||||||||||||
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 planned to only evaluate the HHCs associated with the IPs. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
|
||||||||||||
Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
|
||||||||||||
Number of subjects included in analysis |
2116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | ||||||||||||
Point estimate |
0.73
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.48 | ||||||||||||
upper limit |
1.09 |
|
|||||||||||||
End point title |
Percentage of Households With Any Virological Infection at Household Level by Day 9 | ||||||||||||
End point description |
Virological infection at HH level were defined as the HHs with at least one HHC who met the endpoint of any virological infection by Day 9. PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) to Day 9
|
||||||||||||
|
|||||||||||||
Notes [9] - Number analyzed represents the number of households analyzed for this endpoint. [10] - Number analyzed represents the number of households analyzed for this endpoint. |
|||||||||||||
Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
|
||||||||||||
Comparison groups |
Placebo: Household v Baloxavir Marboxil: Household
|
||||||||||||
Number of subjects included in analysis |
1092
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Odds Ratio (BMX vs Placebo) | ||||||||||||
Point estimate |
0.79
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.59 | ||||||||||||
upper limit |
1.06 |
|
|||||||||||||
End point title |
Percentage of HHCs With Any Virological Infection by Day 9 [11] | ||||||||||||
End point description |
Virological infection was defined as HHCs who tested PCR+ for influenza by Day 9 post IP randomization based on PCR influenza test results. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B and received study drug and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) to Day 9
|
||||||||||||
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 planned to only evaluate the HHCs associated with the IPs. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
|
||||||||||||
Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
|
||||||||||||
Number of subjects included in analysis |
2111
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | ||||||||||||
Point estimate |
0.71
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.53 | ||||||||||||
upper limit |
0.94 |
|
|||||||||||||
End point title |
Percentage of HHCs With Any Symptomatic Infection by Day 9 [12] | ||||||||||||
End point description |
Percentage of HHCs who tested PCR+ for influenza by Day 9 post IP randomization and develop symptoms at any time during the study are reported. HHCs ≥12 years were symptomatic if they had (1) a temperature ≥38.0°C and one respiratory symptom (cough, sore throat, nasal congestion) or (2) one respiratory & one systemic symptom (headache, chills, muscle/joint pain, fatigue), with/without fever. HHCs ≥2 and <12 years were symptomatic with a temperature ≥38.0°C and upper respiratory symptoms (cough, nasal congestion, rhinorrhea). Symptoms must be either new, or have worsened versus baseline in HHC with baseline symptoms due to a preexisting comorbidity. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B and received study drug and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) to Day 9
|
||||||||||||
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 planned to only evaluate the HHCs associated with the IPs. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Baloxavir Marboxil vs Placebo | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
|
||||||||||||
Comparison groups |
Placebo: HHCs v Baloxavir Marboxil: HHCs
|
||||||||||||
Number of subjects included in analysis |
2108
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Adjusted OR (BMX vs Placebo) | ||||||||||||
Point estimate |
0.72
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.49 | ||||||||||||
upper limit |
1.07 |
|
|||||||||||||
End point title |
Percentage of Households With Any Symptomatic Infection at HH Level by Day 9 | ||||||||||||
End point description |
Percentage of HHs with at least one HHC who meets the endpoint of any symptomatic infection by Day 9 are reported. HHCs ≥12 years were symptomatic if they had (1) a temperature ≥38.0°C and one respiratory symptom (cough, sore throat, nasal congestion) or (2) one respiratory & one systemic symptom (headache, chills, muscle/joint pain, fatigue), with/without fever. HHCs ≥2 & <12 years were symptomatic with a temperature ≥38.0°C &upper respiratory symptoms (cough, nasal congestion, rhinorrhea). PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day 1) to Day 9
|
||||||||||||
|
|||||||||||||
Notes [13] - Number analyzed represents the number of households analyzed for this endpoint. [14] - Number analyzed represents the number of households analyzed for this endpoint. |
|||||||||||||
Statistical analysis title |
Placebo vs Baloxavir Marboxil | ||||||||||||
Statistical analysis description |
The OR shown represents the odds of BMX versus the odds of Placebo.
|
||||||||||||
Comparison groups |
Placebo: Household v Baloxavir Marboxil: Household
|
||||||||||||
Number of subjects included in analysis |
1092
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Odds Ratio (BMX vs Placebo) | ||||||||||||
Point estimate |
0.71
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95.38% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.48 | ||||||||||||
upper limit |
1.04 |
|
||||||||||
End point title |
Number of IPs With Adverse Events (AEs) [15] | |||||||||
End point description |
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Safety IP Set included all randomized participants who received at least one dose of study treatment.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)
|
|||||||||
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: Safety data was collected only for the IPs enrolled in the study. |
||||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of IPs With Serious Adverse Events (SAEs) [16] | |||||||||
End point description |
A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. Safety IP Set included all randomized participants who received at least one dose of study treatment.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)
|
|||||||||
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: Safety data was collected only for the IPs enrolled in the study. |
||||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information [1]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to Day 9 (IPs ≥12 years old)
Baseline up to Day 21 (IPs <12 years old)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety IP Set included all randomized participants who received at least one dose of study treatment. Safety data was collected only for IPs as no treatment was administered to the HHCs in this study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo: IPs
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
IPs were randomized in this arm to receive a single dose of matching placebo orally as a tablet or oral suspension based on their weight and age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Baloxavir Marboxil: IPs
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
IPs received a single dose of baloxavir marboxil orally based on their weight and age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no Non-serious adverse events at a 5% threshold in this study. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
11 Jun 2019 |
Protocol amended primarily to update safety information. |
||
10 Aug 2020 |
Protocol amended primarily to expand the pediatric IP population to include IPs 5 to 11 years old, to add SARS-CoV-2 testing at
screening and during the study as applicable, and to exclude and/or withdraw IPs and households who test positive for SARS-CoV-2 during the study. |
||
29 Mar 2022 |
Protocol amended to reduce the requirement from 2 or more HHCs to 1 or more HHCs to participate in the entire duration of the study and who had not received the influenza vaccine within 6 months prior to screening. In addition, IPs who are <12 years old who had received the oral suspension were asked to answer a questionnaire regarding the palatability and acceptability of the study drug. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |