Clinical Trial Results:
A Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of S-217622 in the prevention of symptomatic SARS-CoV-2 infection in household contacts of an individual with symptomatic COVID-19
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Summary
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EudraCT number |
2025-000303-24 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
18 Sep 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jul 2025
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First version publication date |
19 Jul 2025
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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 |
2206T1331
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05897541 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shionogi B.V.
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Sponsor organisation address |
Herengracht 464, Amsterdam, Netherlands, 1017 CA
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Public contact |
shionogiclintrials-admin@shionogi.co.jp, Shionogi B.V., 0044 2030534200, shionogiclintrials-admin@shionogi.co.jp
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Scientific contact |
shionogiclintrials-admin@shionogi.co.jp, Shionogi B.V., 0044 2030534200, shionogiclintrials-admin@shionogi.co.jp
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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-003192-PIP03-23 | ||
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 |
18 Sep 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Sep 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Sep 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 |
To compare ensitrelvir with placebo in the
prevention of symptomatic SARS-CoV-2
infection in participants with a negative
screening SARS-CoV-2 infection who are
household members (hereinafter referred to
as “participants”) of SARS-CoV-2-infected
patients (hereinafter referred to as “index
patients”) through Day 10 (using the mITT
analysis set)
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Protection of trial subjects |
This study will be conducted by all involved parties in accordance with the
protocol and with the following:
– Consensus ethical principles derived from international guidelines, including
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences (CIOMS) International Ethical Guidelines
– Applicable ICH GCP Guidelines
– Applicable laws and regulations (including European regulation 536/2014
Annex I Section D No. 17 lit. a)
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Background therapy |
Prior/Concomitant Therapy - Any medication or vaccine (including over-the-counter or prescription medicines, recreational drugs, vitamins, and/or herbal supplements) or other specific categories of interest that the participant is receiving at the time of enrollment or receives during the study must be recorded in the eCRF. Any medications specific for COVID-19 (other than symptom alleviation treatment) used by the index patient must also be recorded in the eCRF. Other concomitant medications may be considered on a case-by-case basis by the investigator in consultation with the medical monitor. | ||
Evidence for comparator |
Not Applicable | ||
Actual start date of recruitment |
09 Jun 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 1601
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Country: Number of subjects enrolled |
Japan: 614
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Country: Number of subjects enrolled |
Viet Nam: 140
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Country: Number of subjects enrolled |
Argentina: 18
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Country: Number of subjects enrolled |
South Africa: 14
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Worldwide total number of subjects |
2387
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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) |
0
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Adolescents (12-17 years) |
175
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Adults (18-64 years) |
1978
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From 65 to 84 years |
234
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85 years and over |
0
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Recruitment
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Recruitment details |
Dates of recruitment was from 9 June 2023 to 21 August 2024. This study was a multicenter study conducted at 178 contracted sites, including 95 sites in the US, 67 sites in Japan, 2 sites in Vietnam, 11 Sites in Argentina, and 3 sites in South Africa. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Visit 1, Day 1 for the index patient will not necessarily be the same day as Visit 1, Day 1 for the participant. However, the participant must provide informed consent ≤ 72 hours from onset of COVID-19 symptoms in the index patient and ≤ 1 calendar day from the time that the index patient provides consent. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active | ||||||||||||||||||||||||||||||
Arm description |
S-217622 at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5 | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ensitrelvir
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Investigational medicinal product code |
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Other name |
S-217622
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
S-217622 at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Placebo at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5 | ||||||||||||||||||||||||||||||
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 |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active
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Reporting group description |
S-217622 at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5 | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo at a dose of 375 mg for Day 1 and 125 mg once daily for Days 2 to 5 | ||
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End point title |
Proportion of participants in the mITT analysis set with a negative screening SARS-CoV-2 infection (CLC-negative RT-PCR test) who are infected with SARS-CoV-2 (CLC-positive RT-PCR test) and have COVID-19 symptoms onset through Day 10 | |||||||||
End point description |
Proportion of participants in the mITT analysis set with a negative screening SARS-CoV-2 infection (CLC-negative RT-PCR test) who are infected with SARS-CoV-2 (CLC-positive RT-PCR test) and have COVID-19 symptoms onset through Day 10
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End point type |
Primary
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End point timeframe |
Ten Days
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| Notes [1] - S-217622 [2] - Placebo |
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Statistical analysis title |
Risk for Symptomatic COVID-19 Through Day 10 | |||||||||
Statistical analysis description |
The null hypothesis to be tested was that the risk for
incident symptomatic COVID-19 over 10 days in participants assigned to treatment with
ensitrelvir is the same compared to the risk for incident symptomatic COVID-19 over
10 days in participants assigned to treatment with a matching placebo.
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Comparison groups |
Active v Placebo
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Number of subjects included in analysis |
2387
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | |||||||||
P-value |
< 0.0001 [4] | |||||||||
Method |
GEE Poisson Regression Model | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.33
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.22 | |||||||||
upper limit |
0.49 | |||||||||
Variability estimate |
Standard error of the mean
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| Notes [3] - GEE Poisson Regression Model [4] - Statistically significant |
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Adverse events information [1]
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Timeframe for reporting adverse events |
7 days for fatal or life threatening SAE reports
15 days all other SAE reports
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
26
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| Frequency threshold for reporting non-serious adverse events: 1% | |||
| 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: Non-serious adverse events in 300 study participants on ensitrelvir and 305 study on placebo. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 Oct 2022 |
The primary purpose of this protocol amendment is to add clarifications to improve study implementation. For example, the requirement for the amount of time from informed consent to randomization was changed from ≤ 96 hours to ≤ 72 hours. |
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19 Apr 2023 |
The primary purpose of this protocol amendment is to incorporate recommendations from the regulatory agency |
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30 Oct 2023 |
The primary purpose of this protocol amendment is to add a data safety monitoring board (DSMB) and to incorporate changes in response to health authority requests |
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03 Nov 2023 |
The primary purpose of this protocol amendment is to add a data safety monitoring board (DSMB), include changes consistent with the country-specific amendment (2.1 – EU), and to make study clarifications. |
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08 Jul 2024 |
The primary purpose of this protocol amendment is to clarify that the sample size may vary from the original estimate. As per the original protocol, the sample size was to be determined based on the targeted number of events (92 events) and was permitted to be
adjusted to ensure the targeted number of events was achieved. |
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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 | |||
