Evaluation of S-337395 Efficacy and Safety in High-Risk Nonhospitalized Adults with Respiratory Syncytial Virus: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2025-523156-31-00
- Protocol
- 2402T1432
- Sponsor
- Shionogi B.V.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the antiviral effect of S-337395 in adults with respiratory syncytial virus infection. The secondary objectives include:
- Assessment of safety and tolerability following administration.
- Evaluation of the effect on clinical symptoms.
- Investigation of additional antiviral outcomes beyond the primary endpoint.
- Analysis of the pharmacokinetics of S-337395.
Participants
This study involves 172 participants diagnosed with Respiratory Syncytial Virus. The study population consists of male and female patients aged 18 years or older. Eligible individuals are those with a confirmed diagnosis of RSV infection, preferably identified via polymerase chain reaction or other molecular-based diagnostic assays. Participants must be medically stable based on medical history, physical examination, vital signs, and 12-lead ECG, with any abnormalities being consistent with the underlying illness. Required contraceptive measures include adherence to local regulations and specific requirements for male participants regarding semen donation and barrier methods. All participants must be capable of providing informed consent and demonstrating compliance with study procedures and concomitant medication restrictions.
Plans and Procedures
This phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study is designed to evaluate the safety, tolerability, and efficacy of S-337395 in symptomatic nonhospitalized adults diagnosed with respiratory syncytial virus who are at high risk of progression to severe disease. The primary objective is to investigate the antiviral effect of the investigational product. The research methodology includes a screening visit to assess eligibility via medical history, physical examination, vital signs, 12-lead ECG, and molecular-based diagnostic assays such as polymerase chain reaction. Following inclusion, participants will undergo several study visits to monitor changes in RSV RNA load via nasopharyngeal swabs on day 2, day 4, and day 6. Secondary endpoints involve the assessment of treatment-emergent adverse events, clinical laboratory results, and the severity of symptoms using the RiiQ scale. Participant involvement is centered around the administration of the intervention and subsequent follow-up assessments to determine the time to symptom resolution and plasma concentrations of the study drug.
Treatment
The experimental treatment consists of S-337395. The specific pharmaceutical form, dosage, and route of administration for this substance are not specified in the provided data.
The control group receives a placebo as part of a double-blind, placebo-controlled study design to evaluate the antiviral effect in patients with respiratory syncytial virus.
Efficacy
The efficacy of S-337395 will be evaluated by measuring the change from baseline in respiratory syncytial virus (RSV) RNA load using qRT-PCR from nasopharyngeal swabs. This primary endpoint will be assessed on day 2, day 4, and day 6.
Secondary efficacy assessments include:
- Change from baseline in the severity of symptoms using the RiiQ™ instrument, specifically the respiratory symptom score (RiiQ-RSS), systemic symptom score (RiiQ-SSS), and the total score.
- Time to resolution, defined as the return to baseline per the PSQ, including time to first and sustained resolution of respiratory, systemic, and combined symptoms.
- Changes in infectious titer and RNA load via virological assay, including the area under the curve (AUC) through day 6 and time to first or sustained negative results.
- Plasma concentrations of S-337395 following repeated oral doses, specifically measured at 12 and 24 hours after the first and last doses.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 1. Participant must be ≥ 18 years of age (or the minimum age of informed consent if the minimum age of informed consent determined by local regulations is >18 years) at the time of screening.
- Type of Participant and Disease Characteristics 3. Participants diagnosed with RSV infection preferably using a rapid polymerase chain reaction (PCR) or other molecular-based diagnostic assay. Note: If a participant had a positive RSV test result using a molecular-based diagnostic assay from another study for which he/she was otherwise ineligible or from a standard-of-care molecular-based diagnostic test within 72 hours prior to start of screening and meets all eligibility criteria for inclusion in this study, this diagnostic test result can be used for determination of eligibility. 5. With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, vital signs, and 12-lead ECG performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and/or the RSV infection.
- Sex and Contraceptive/Barrier Requirements The following criteria apply to male and female participants: 6. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for those participating in clinical studies. Men must refrain from semen donation a. Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 10 days after the last dose of investigational intervention: ● Refrain from donating fresh unwashed semen PLUS either: ● Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR ● Must agree to use contraception/barrier as detailed below – Agree to use a male condom when having sexual intercourse with a woman of childbearing potential who is not currently pregnant – Agree to use a male condom when engaging in any activity allowing for passage of ejaculate to another person
- Informed Consent 7. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1.3), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Each participant has signed an ICF indicating he/she: a. Understands the purpose of, and procedures required for, the study b. Is willing and able to adhere to the prohibitions and restrictions with respect to the concomitant medication c. Is willing and able to adhere to the study procedures and assessments to be performed
Exclusion Criteria
- Hospitalized or expected to be hospitalized within 24 hours of screening. Any stay in the emergency room or in the observational unit of at least 24 hours will be considered hospitalization for the purposes of the study.
- Is considered by the investigator to be immunocompromised, due to an underlying medical condition (eg, HIV infection, malignancy, or genetic disorder other than immunoglobulin A deficiency) or medical therapy (eg, immunomodulators other than corticosteroids for the treatment of COPD or asthma exacerbations), chemotherapy, radiation, stem cell or solid organ transplant
- Major surgery within 28 days prior to enrolment in the study or planned major surgery during the study
- Has a neuromuscular disease affecting swallowing or the thoracic muscles
- Has a known or clinically suspected acute or chronically active hepatitis B or C infection
- Has known allergies, hypersensitivity, or intolerance to S-337395 or to any of the excipients of the S-337395 or placebo formulation
- Suspicion or known severe renal impairment (defined as estimated glomerular filtration rate < 30 mL/min/1.73 m2) or ongoing dialysis
- Aspartate aminotransferase or alanine aminotransferase > 3 times the upper limit of normal (ULN) or total bilirubin ≥ 2 × ULN (except for Gilbert syndrome) within the past 3 months, active liver disease (except direct bilirubin > ULN), or the presence of liver dysfunction grade B or C according to the Child-Pugh classification
- Any other medical or psychiatric condition making the participant unsuitable for the current study or interfering with the evaluation of response to the study intervention in the opinion of the investigator/subinvestigator
- Prior/Concomitant Therapy 13. Has received a therapy intended to treat RSV infection (eg, ribavirin, traditional Chinese medicines, or complementary therapies) within 14 days prior to screening
- Is receiving chemotherapy or immunotherapy for malignancy
- Has received RSV vaccination within 7 days prior to screening Note: RSV vaccination is not prohibited, unless administered within 7 days prior to screening.
- Prior/Concurrent Clinical Study Experience 16. The participant is currently participating or planned to participate in another clinical interventional study, during their participation in this study.
- Diagnostic Assessments 17. Has had either confirmed SARS-CoV-2 or influenza infection (test was positive) during the 28 days prior to screening,
- Has any other confirmed clinically relevant respiratory infection by any pathogen at, or within 28 days of screening
- Other Exclusion Criteria 19. Women who are of childbearing potential
- Men who plan to father a child while enrolled in this study or within 10 days after the last dose of study intervention
- Participants unable to take medications orally or with a known gastrointestinal-related condition considered by the sponsor or investigator to be likely to interfere with study intervention ingestion or absorption
- Participants unwilling to undergo nasal nasopharyngeal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens
- At the US sites, site staff and their families who are directly involved in the conduct of the study, site staff who are otherwise under the supervision of the investigator, and sponsor and sponsor representative employees and their families who are directly involved in the conduct of this study. For sites in all other countries, apply local country regulations.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 01 Dec 2025 | 30 |
 Poland | Not Yet Recruiting | 01 Dec 2025 | 10 |