Clinical trial NCT05970744: Evaluation of RSV/Flu-01E Vaccine for the Prevention of RSV Infection in Volunteers Aged 18 to 59 Years and Over 60 Years
Official title: Randomized, Double-blind, Placebo-controlled Phase 1 Trial of the RSV/Flu-01E Vaccine for the Prevention of Respiratory Syncytial Virus Infection in Volunteers Aged 18 to 59 Years and Over 60 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory syncytial virus infection
Vaccine
Influenza vector
Intranasal immunization
Lead sponsor: Research Institute of Influenza, Russia
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study is to investigate the safety and immunogenicity of the RSV/Flu-01E vaccine for the prevention of respiratory syncytial virus infection in volunteers aged18 to 59 years and over 60 years.

Detailed description: Study includes 60 participants in three cohorts. First cohort includes 15 volunteers aged 18 to 59, randomized at 2:1 ratio, to receive low dose RSV/Flu-01E vaccine or placebo, correspondingly. Second cohort includes 15 volunteers aged 18 to 59, randomized at 2:1 ratio, to receive high dose RSV/Flu-01E vaccine or placebo, correspondingly. Third cohort includes 30 participants aged 60 years and older, randomized at 2:1 ratio to receive high dose RSV/Flu-01E vaccine or placebo. Duration of the study for each participant is about 6 months (no more than 190 days).

Eligibility criteria: Inclusion Criteria:

For the first and second cohort:

1. Availability of signed informed consent.
2. Adult men and women aged 18-59 years.
3. Diagnosed "healthy", according to the data of standard clinical, laboratory and instrumental examination methods provided for in this protocol, with the absence of clinically significant changes.
4. BMI from 18 to 30 kg/m2.
5. Individuals with antibody titer to influenza A/H1N1pdm09 ≤1:20 according to HI assay.
6. Ability and willingness to independently keep records in the diary of self-observation and carry out all visits according to the protocol.
7. Negative urine test for psychotropic and narcotic substances.
8. Negative breath alcohol test.
9. Consent of study participants to use effective contraceptive methods throughout their participation in the study. In this study, volunteers can use the following methods of contraception:

   * Combined methods:

     * male condom and spermicide
     * cervical cap and spermicide
     * vaginal diaphragm and spermicide
   * Intrauterine device
   * Hormonal intrauterine device
   * Hormonal contraceptives:

     * hormonal implants
     * hormone injections
     * combined oral contraceptives
     * mini-pill
     * contraceptive patch
   * Abstinence from sexual activity.
10. For women of childbearing potential - a negative pregnancy test.
11. Indicators of general and biochemical blood tests at screening within 1.1 x the upper limit - 0.9 x the lower limit of the reference intervals.
12. Negative tests for HIV, hepatitis B and C, syphilis.

For the third cohort:

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. Individuals with antibody titer to influenza A/H1N1pdm09 ≤1:20 according to HI assay.
6. The ability and readiness to independently keep records in the diary of self-observation and carry out all the visits provided for in the study, provided for by the protocol.
7. Negative urine test for psychotropic and narcotic substances.
8. Negative breath alcohol test.
9. Indicators of general and biochemical blood tests for screening within 1.1 x the upper limit - 0.9 x the lower limit of the reference intervals.
10. Negative tests for HIV, hepatitis B and C, 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. Anatomical features of the nose that may interfere with intranasal administration of the study drug
8. The presence of surgical intervention in the sinus area, paranasal sinuses, or traumatic injuries of the nose within a month before screening.
9. Symptoms of acute respiratory disease 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. Burdened allergic anamnesis.
19. 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.
20. History of oncological diseases.
21. History of thrombocytopenic purpura or bleeding disorders.
22. History of convulsions
23. Tuberculosis or residual changes after tuberculosis according to the anamnesis and / or available medical documentation.
24. Chronic alcohol dependence or chronic use of illicit drugs, drug abuse.
25. Claustrophobia and social phobia according to history and / or available medical records.
26. For women of reproductive age - lactation, pregnancy or suspected pregnancy, early postpartum period.
27. Inability to read in Russian; inability or unwillingness to understand the essence of the study. Any other condition that limits the eligibility of obtaining informed consent or may affect the volunteer's ability to participate in the study.
28. Military or law enforcement officers, persons serving sentences in places of deprivation of liberty or in custody.
29. Special diet (eg, vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical activity)
30. 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

Primary outcomes:
measure: Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Throughout the study, average of 6 months
Secondary outcomes:
measure: Level of RSV F antigen-specific cytokine producing T-cells
timeFrame: Days 1, 7, 28, 90, 180
measure: Level of RSV F antigen-specific cytokine release in whole blood assay
timeFrame: Days 1, 7, 28
measure: Level of RSV F antigen-specific mucosal IgA antibody in saliva/nasal secrets
timeFrame: Days 1, 28
measure: Level of RSV F antigen-specific IgG antibody
timeFrame: Days 1, 28, 90, 180
measure: Proportion of responders to vaccination
timeFrame: Days 7, 28
measure: Concentration of cytokines in nasal secrets after vaccination
timeFrame: Days 1, 2, 3
measure: Influenza specific systemic antibody immune response
timeFrame: Days 1, 28
measure: Influenza specific local antibody immune response
timeFrame: Days 1, 28
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Smorodintsev Research Institute of Influenza
Study officials:
affiliation: Smorodintsev Research Institute of Influenza
name: Tatiana Zubkova, PhD
role: PRINCIPAL_INVESTIGATOR
References: