Establishing a Controlled Human Infection Model (CHIM) with a Rhinovirus challenge agent in healthy volunteers

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 40

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. Subject has adequate understanding of the procedures of the study and agrees
to abide strictly thereby;
6. Subject is able to communicate well in Dutch with the investigator, and
is willing to comply with the study procedures and restrictions;
7. Subject is able to tolerate the nasal wash procedure at screening;
8. Seronegative (Virus neutralizing titer <= 1:6) for RV16 at screening for part
A; seropositive for RV16 (VNT >1:6) at screening in part B;
9. Willingness to stay in self-quarantine between baseline visit and day of
inoculation.

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 subject 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) will 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 the study. Exceptions are paracetamol (up to
4 gram/day) and contraceptives. Other exceptions will only be made if the
rationale is clearly documented and accepted by the investigator.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To identify the inoculation dose needed to induce rhinovirus infection in 80%<br /><br>of exposed healthy adult volunteers without pre-existing immunity to RV16.<br /><br><br /><br>Primary endpoints for the primary objective:<br /><br>• Infection rate (number and frequency of subjects with rhinovirus infection as<br /><br>assessed by PCR) for each inoculation dose in subjects seronegative for RV16<br /><br>(part A)</p><br>

Secondary Outcome Measures