Respiratory tract infections Virale infecties
Conditions
Interventions
Volunteers will be inoculated intranasally with escalating doses of the
GMP-produced wild-type RV16-strain.
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure; 2. Healthy male or female volunteers, 18 to 49 years of age, inclusive at screening; Good health is based upon the results of medical history, physical examination, vital signs, ECG, and laboratory profiles of both blood and urine 3. A total body weight >=50 kg and body mass index (BMI) >=18.0 and <=30.0 kg/m2 at screening; 4. All women of child bearing potential and must practice effective contraception during the course of the study; 5. Participant has adequate understanding of the procedures of the study and agrees to abide strictly thereby; 6. Participant is able to communicate well in Dutch with the investigator, and is willing to comply with the study procedures and restrictions; 7. Seronegative (Virus neutralizing titer <= 1:6) for RV16 at screening for part A; seropositive for RV16 (VNT >1:6) at screening in part B; 8. Willingness to stay in self-quarantine between baseline visit and day of inoculation.
Exclusion criteria
Exclusion criteria: 1. Any history or evidence of any clinically significant or currently active major disease, or condition that, in the opinion of the investigator, may interfere with a participant completing the study and the necessary investigations (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, and body temperature) and ECG). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance; 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including blood biochemistry, hematology and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before inclusion to confirm eligibility or judged to be clinically irrelevant; 3. Chronic respiratory disease (asthma, emphysema, COPD, chronic rhinitis or sinusitis or other reactive airway diseases) in adulthood. Childhood asthma and non-active allergic rhinitis (including hay fever) may be permitted at the discretion of the investigator; 4. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening; 5. Any confirmed or suspected disease or condition associated with immune system impairment, including auto-immune diseases, HIV, asplenia or recurrent severe infections; 6. Prior inoculation with a virus from the same virus family as the challenge virus; 7. 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; 8. Participation in an investigational medical product, vaccine or device study within 3 months or 5 half-lives prior to the study period (whichever is longer), or more than 4 times in the past year; 9. Any known history of anaphylaxis or any significant allergy against the excipients of the virus challenge inoculum; 10. 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; 11. History of frequent epistaxis (nose bleeds) in the six months prior to inoculation and/or any history of being hospitalized due to epistaxis; 12. Any nasal or sinus surgery within 3 months prior to the viral challenge; 13. Upper or lower respiratory tract infection or febrile illness (temperature >=37.9°C), in the period of 2 weeks prior to the viral challenge; 14. Symptoms of active hay fever or other allergies that involve the airways, during screening, prior to inoculation or expected during the investigational period based on prior seasonality; 15. Use of any medications (prescription or over-the-counter [OTC]), within 14 days prior to virus inoculation, or less than 5 half-lives (whichever is longer), and during the course of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To identify the inoculation dose needed to induce rhinovirus infection in 80% of exposed healthy adult volunteers without pre-existing immunity to RV16. Primary endpoints for the primary objective: • Infection rate (number and frequency of subjects with rhinovirus infection as assessed by PCR) for each inoculation dose in participants seronegative for RV16 (part A) | — |
Secondary
| Measure | Time frame |
|---|---|
| • To investigate the safety and tolerability of controlled infection after inoculation with RV16 • To identify the inoculation dose needed to induce symptomatic rhinovirus infection in exposed healthy adult volunteers without pre-existing immunity to RV16. • To assess the rhinovirus kinetics in nasal wash, nasal swab and saliva • To assess the effect of background immunity on rhinovirus kinetics in nasal wash, swab and saliva (part B) • To characterize the disease severity and duration of RV16 challenge in healthy adult volunteers • To assess the effect of background immunity on disease severity and duration (part B) Secondary endpoints for the secondary objectives: • Nature, frequency and severity of (serious) adverse events • Self-reported symptoms (assessed by the Jackson score and WURSS-21 questionnaire) that are classified as severe. • Clinical laboratory test • Vital signs • Physical examination, symptom directed and on indication • Concomitant medication • Self-reported nasal pain assessed by a visual analogue scale (VAS) • Attack rate for each inoculation dose in participants seronegative for RV16 at baseline (part A) • Rhinovirus viral load onset, peak and duration as determined by serospecific qPCR • Self-reported symptoms assessed by the Jackson score and WURSS-21 questionnaire. These symptoms will not be reported as adverse events. • Infection rate for each inoculation dose in participants seropositive for RV16 (part B) • Attack rate for each inoculation dose in participants seropositive for RV16 (part B) | — |
Countries
Netherlands
Contacts
Public ContactI.M.C. Visser-Kamerling
Centre for Human Drug Research
Outcome results
None listed