Phase 2 Study of the RSV/Flu-01E Vaccine Against Respiratory Syncytial Virus Infection in Older Adults

Randomized, Double-blind, Placebo-controlled Phase 2 Trial of RSV/Flu-01E Vaccine for the Prevention of Respiratory Syncytial Virus Infection in Volunteers Over 60 Years

The aim of the study is to investigate immunogenicity and safety of the RSV/Flu-01E intranasal vaccine for the prevention of respiratory syncytial virus infection in volunteers over 60 years

Study Overview

• Status: Completed
• Conditions: Respiratory Synctial Virus Infections
• Intervention / Treatment: Biological: RSV/Flu-01E; Other: Placebo

Detailed Description

Study includes 120 participants over 60 years randomized at 3:1 ratio, to receive single intranasal dose of RSV/Flu-01E vaccine or placebo, correspondingly. Duration of the study for each participant is about 4 months (118±3 days)

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • St Petersburg, Russian Federation, 197022
    • Smorodintsev Research Institute of Influenza
  • St Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • St Petersburg, Russian Federation, 197198
    • St. Petersburg City Polyclinic No. 34

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Availability of signed informed consent
2. Adult men and women over the age of 60.
3. The diagnosis is "healthy", verified according to standard clinical, laboratory and instrumental methods of examination or the presence of a chronic disease, if the researcher considers it to be compensated.
4. BMI from 18 to 30 kg/m2.
5. The ability and willingness to make entries in the diary of self-observation, as well as to carry out all the visits foreseen in the study for control medical observation
6. Negative test for alcohol in exhaled air
7. Values of the complete blood count and biochemical blood analysis (during the screening) within 0.9*reference range lower limit and 1,1 * reference range upper limit
8. Negative tests for HIV, hepatitis B, hepatitis C, and syphilis

Exclusion Criteria:

1. Participation in another clinical study within three months prior to the start of the current study; planning to participate in another study during the current study period
2. Contact with COVID-19 patients within 14 days prior to the start of the clinical study
3. Positive rapid test result for SARS-CoV-2 antigen
4. Immunization with any other non-study vaccine product within three weeks prior to enrollment in the current study, or refusal to postpone such until the end of the three-week period after completion of the current study
5. Regular use of nasal irrigation therapy during the last six months prior to enrollment in the current study or episodic use of the above method of treatment in the two weeks prior to the screening
6. History of frequent nosebleeds (>5) during the year prior to the current study
7. Features of the nasal anatomy that may complicate intranasal administration of the study drug
8. Surgical interventions or traumatic injuries in the sinus area, paranasal sinuses, or traumatic injuries of the nose within a month before screening
9. Symptoms of acute respiratory disease, including fever, or other acute illness at the time of screening or within two weeks prior to screening
10. Treatment with immunoglobulins or other blood derived medications in the three months prior to screening or planning such treatment during the period of participation in the current study
11. Donation of blood/plasma (450 ml or more) less than 2 months prior to screening.
12. The presence or suspicion of the presence of various immunosuppressive or immunodeficiency conditions or continuous use (the drug was prescribed for more than 14 days without a break) of immunosuppressive drugs, immunomodulators for 6 months before the screening.
13. History of bronchial asthma
14. Hypersensitivity and the presence of severe allergic reactions, including Quincke's edema, anaphylactic shock after the previous administration of any vaccine
15. History of wheezing after previous immunization with live influenza vaccine
16. Other adverse events after immunization (fever above 40°C, syncope, non-febrile convulsions, anaphylaxis) when there is a minimal likelihood that they are associated with a previous administration of any vaccine
17. Suspicion of hypersensitivity to any component of the study vaccine, including egg protein
18. Acute or chronic clinically significant lung, cardiovascular, hepatic, endocrine, neurological, or psychiatric disorders, or impaired renal function identified by history, physical examination, or clinical laboratory findings that, in the opinion of the investigator, may influence the outcome of the study
19. History of oncological diseases
20. History of thrombocytopenic purpura or bleeding disorders
21. History of convulsions
22. Tuberculosis or residual changes after tuberculosis according to the anamnesis and / or available medical documentation
23. Chronic alcohol dependence or chronic use of illicit drugs, drug abuse
24. Claustrophobia and social phobia according to history and / or available medical records
25. Inability to read Russian; inability or unwillingness to understand the essence of the study
26. Military personnel serving in the military or law enforcement officers.
27. Special diet (eg, vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical activity)
28. Any condition that, in the opinion of the investigator, may increase the risk to the health of a volunteer participating in the study or affect the results of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single dose of Placebo	Other: Placebo; Participants will receive single intranasal injection of physiological buffer solution in 0.5 ml
Experimental: RSV/Flu-01E; Single dose of RSV/Flu-01E vector vaccine	Biological: RSV/Flu-01E; Participants will receive single intranasal injection of RSV/Flu-01E vaccine in 0.5 ml, containing 8.4 lg EID50 of A/H1N1pdm09 recombinant attenuated influenza vector with modified NS gene, encoding for the F antigen of respiratory syncytial virus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of RSV F antigen-specific cytokine producing CD4+ and CD8+ T-cells	Change from baseline in the level of cytokine producing CD4+ and CD8+ T-cells upon in vitro stimulation of PBMC with RSV F-peptide epitopes measured by FACS/ELISPOT	Days 1, 7, 28
Level of the RSV F antigen-specific Th1/Th2 cytokine release in whole blood assay	Change from the baseline of the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with RSV F-peptide epitopes measured in ELISA	Days 1, 7, 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs)	Adverse events (AEs) and serious AEs (SAEs), both vaccine related, and non-vaccine related; AEs/SAEs of particular importance: Immediate AEs (allergic reactions) occurring within two hours of vaccination.; Post-vaccination reactions (anticipated clinical manifestations of a local and systemic nature), usually due to intranasal vaccination between two hours and the next 7 days after vaccination	Throughout the study, average 4 months
Concentration of cytokines in nasal secrets after vaccination	Change from baseline in the concentration of cytokines in nasal secrets measured in ELISA	Days 1, 2, 3
Level of RSV F antigen-specific IgG antibody in serum	Change from the baseline in the level of RSV F antigen-specific serum IgG antibodies measured in ELISA	Days 1, 28, 118±3
Influenza specific systemic antibody immune response	Change from the baseline in the titer of influenza specific antibodies in serum measured in hemagglutination inhibition/microneutralization assay	Days 1, 28, 118±3
Level of mucosal IgA antibody in nasal secret	Change from the baseline in the level of IgA antibody measured in ELISA in nasal secret	Days 1, 28
Level of influenza specific cytokine release in whole blood assay	Change from the baseline of the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with influenza A/H1N1pdm antigen measured in ELISA	Days 1, 7, 28
Level of B-cell populations	Change from the baseline in the relative amount of B-cell populations in PBMC measured by FACS	Days 1, 7, 28

Collaborators and Investigators

• Sponsor: Research Institute of Influenza, Russia
• Collaborators: Pavlov First Saint Petersburg State Medical University; St. Petersburg City Polyclinic No. 34
• Investigators: Study Director: Marina Stukova, Dr, Smorodintsev Research Institute of Influenza

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2023
• Primary Completion (Actual): January 8, 2024
• Study Completion (Actual): April 8, 2024

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Respiratory syncytial virus infection; Mucosal Vaccine; Influenza Vector; Intranasal Immunization
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; RNA Virus Infections; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Infections; Communicable Diseases; Virus Diseases; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: RSV-II-06/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only IPD used in the results publication will be available
• IPD Sharing Access Criteria: IPD will be available upon reasonable request to Study Director. Once the request is approved, the data can be transferred via a secure online platform

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No