RSV infection
Conditions
Interventions
GMP-produced wild-type RSV-B-I54 strain, that was isolated in a male pediatric patient patient of 21 months old, admitted to the Utrecht University Medical Centre (UMCU) hospital in 2022, with parenta
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-55 years at screening;2. A total body weight =50 kg and body mass index (BMI) =18.0 and =32.0 kg/m2;3. Good health, based upon the results of medical history, physical examination, vital signs, ECG, and laboratory profiles of both blood and urine, as determined by the investigator;4. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby;5. Subject is able to communicate well with the investigator, and is willing to adhere to study procedures and measures regarding self-isolation;6. The following inclusion criteria are applicable to subjects undergoing viral challenge who are in a sexual relationship:a. Female subjects must have a negative pregnancy test at screening and just prior to the date of viral challenge;b. Female subjects of childbearing potential must be using contraception consisting of an acceptable form of birth control starting from at least 2 weeks prior virus inoculation and continuing throughout the study duration (until Day 90);c. Female subjects who are not of childbearing potential;7. Subject has signed informed consent form prior to any study procedures.
Exclusion criteria
Exclusion criteria: 1. Prior inoculation with a virus from the same virus family (Pneumoviridiae) as the challenge virus;2. Prior participation in another controlled human infection study with a respiratory virus in the preceding 6 months taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study;3. Share household, work closely or have close contact with infants (<4 years of age), pregnant women, immune-compromised and/or clinically vulnerable elderly (=65 years old) individuals for 30 days after RSV inoculation;4. Any history of physician-diagnosed and/or objective test-confirmed asthma, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, or chronic lung condition of any aetiology. A history of childhood asthma without respiratory disease in adulthood may be accepted;5. Nasopharyngeal swab indicative for Influenza or other respiratory virus infection, including asymptomatic positive PCR test for SARS-CoV-2, determined by PCR at baseline visit (day -1);6. Upper or lower respiratory tract infection or febrile illness (temperature =37,9°C), in the period of 4 weeks before virus inoculation;7. Receipt of any vaccine within 28 days prior virus inoculation or during the study period, until the last follow-up visit (Day 90); receipt of an RSV vaccine at any time or planned RSV vaccination in the 3 months following virus inoculation;8. Females who are breastfeeding, or have been pregnant within 6 months prior to the study, or have a positive pregnancy test at any point during screening or prior to viral challenge, or are planning to become pregnant during the study;9. Any confirmed or suspected disease or condition associated with immune system impairment, including auto-immune diseases, HIV, asplenia or recurrent severe infections;10. Prior use or planned receipt of immunosuppressive medication (systemic and intranasal glucocorticoids six months prior to inclusion or any other systemic immunosuppressive medication at any time), immunoglobulins or systemic antiviral therapy;11. Symptoms of active hay fever or other allergies that involve the airways, during screening or prior to inoculation;12. Any known history of anaphylaxis or any significant allergy against the excipients of the virus challenge inoculum (sucrose, phosphate-buffered saline);13. Any anatomic or neurologic abnormality impairing the gag reflex, or associated with an increased risk of aspiration, or any abnormality significantly altering the anatomy of the nose or nasopharynx in a substantial way that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge;14. History of frequent epistaxis (nose bleeds) in the six months prior to inoculation and/or history of being hospitalized due to epistaxis on any previous occasion;15. Any nasal or sinus surgery within 3 months of the date of viral challenge;16. Smokers or ex-smokers with more or equal to 5 pack years smoking history.17. Any smoking in the 30 days preceding screening, including e-cigarettes;18. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent;19. Positive test for illicit drug use at screening or prior to inoculatio
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| To assess the RSV shedding kinetics in nasal swabTo characterize RSV disease after inoculation with a GMP-produced wild-type RSV-B strainTo evaluate the systemic and mucosal immune response | — |
Primary
| Measure | Time frame |
|---|---|
| To establish a controlled human infection model for RSV-B for future drug and vaccine testingTo investigate the safety and tolerability of controlled infection after inoculation with the GMP-produced wild-type RSV-B strainTo identify the inoculation dose of a new, GMP-produced wild-type RSV-B strain, needed to induce RSV infection and with a new strain in 50-70% of exposed healthy adult volunteers | — |
Countries
Netherlands
Contacts
Public ContactI.M.C. Visser-Kameling
Centre for Human Drug Research
Outcome results
None listed