A Dose-Finding and Longitudinal Biomarker Study of Rhinovirus Challenge in Healthy Volunteers and Mild-Moderate Asthmatics to Evaluate the Safety and Use of a Human Rhinovirus Preparation in Developing High Dimensionality Phenotypes (*Handprints*) for Asthma

Completed

• Conditions: asthma; dyspnea; respiratory disease; 10006436

• Registration Number: NL-OMON41599
• Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 49

Inclusion Criteria

1. be willing to give written informed consent for the study - including future
biomedical research on collected samples;
2. be able to read, comprehend, and write at a sufficient level to complete study
materials;
3. be willing to complete the study and all measurements;
4. be male or female, aged 18 to 55 years of age (inclusive) at the pre-trial (screening)
visit
5. have a Body Mass Index (BMI) * 35 kg/m2 and > 17 kg/m2. BMI <= weight
(kg)/height (m)2.
6. for the purpose of safe participation, be judged to be in good health (except for
allowable asthma) based on medical history, physical examination, vital signs, and
laboratory safety tests (Section 7.1.3.1) performed at the pre-trial (screening) visit
and/or prior to the rhinoviral challenge.
7. if a female subject, be one of the below:
- of childbearing potential and must demonstrate a serum *-hCG level consistent
with the nongravid state at the pre-trial (screening) visit and agree to use (and/or
have their partner use) two (2) acceptable methods of birth control beginning at
the pre-trial visit throughout the trial and until 10 days after the last study visit.
- of non-childbearing potential: a female who is postmenopausal without menses
for at least 1 year and an FSH level in the postmenopausal range at the pre-trial
(screening) visit and/or a female who is status-post hysterectomy, status-post
bilateral oophorectomy, or status-post bilateral tubal ligation without reversal
based on the subject*s recall of their medical history. Information must be
captured appropriately within the site's source documents.
8. be a nonsmoker or has not smoked in the past 12 months with a smoking history of
* 10 pack-years;
9. be willing to comply with the trial restrictions (see Section 5.7 for a complete
summary of trial restrictions).
10. have anti-hRV16 titers * 1:4 at the screening visit;
11. have negative nasal lavage rhinovirus PCR results prior to virus challenge;
Part 1:
12. be one of the following:
a. For healthy panels: healthy subject (may have out-of-season seasonal
allergies)
b. For asthmatic panels: mild-moderate asthmatic with the below** criteria
Part 2:
13. have a diagnosis of mild-moderate asthma with the below** criteria.
** Inclusion Criteria for Mild-Moderate Asthmatics
(must be documented within the past five (5) years)
-- Diagnosis of asthma based on one or more of:
. Methacholine PC20 < 8 mg/mL
. Improvement in FEV1 after inhalation of 400mcg salbutamol of *12% of
predicted value, and/or 200mL.
. diurnal variation in peak expiratory flow (PEF) >8% of mean of twice-daily
PEF
. decrease in prebronchodilator FEV1 *12% of predicted FEV1 and/or 200mL after
tapering off of inhaled corticosteroids (ICS), oral glucocorticoids, long-acting
bronchodilator, or regular short-acting bronchodilator.;Note: in cases where either FEV1 or %FEV1 (but not both) changed by the amount specified above, admission of the candidate requires assent of the Sponsor.;AND
. a history of spontaneous or exertional wheezing
-- Controlled disease based on:
. pre-bronchodilator FEV1 * 80% predicted (may be established at screening)
AND having all the below for >4 weeks prior to screening
. daytime symptoms twice weekly or less
. no activity limitation
. no nocturnal symptoms
. use of relie

Exclusion Criteria

1. is mentally or legally institutionalized / incapacitated, has significant emotional
problems at the time of pre-trial (screening) visit or expected during the conduct of
the trial or has a history of clinically significant psychiatric disorder of the last 3
years. Subjects who have had situational depression may be enrolled in the trial at the
discretion of the investigator;
2. has a history of clinically significant endocrine, gastrointestinal, cardiovascular,
hematological, hepatic, immunological, renal, respiratory, genitourinary or major
neurological (including stroke and chronic seizures) abnormalities or diseases;
-- Asthma as defined in the inclusion criteria for some participants in Part 1 and all
participants in Part 2 is allowed.
-- Subjects with a history of uncomplicated (spontaneously evacuated, without
infection) kidney stones, cholecystectomy or childhood asthma (the latter only for the
healthy volunteer panels) may be enrolled in the trial at the discretion of the
investigator.
3. has a history of cancer (malignancy) with the exception of uncomplicated basal cell
carcinoma of the skin or cervical intraepithelial neoplasia - resolved for at least 5
years and not having required chemotherapy or immunomodulation;
4. has a history of severe or difficult to manage allergies (e.g. food, drug, latex allergy),
or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription
drugs or food, that in the opinion of the investigator would pose an undue
risk to the subject;
5. has (or is expected to have) symptomatic seasonal or perennial rhinitis or sinusitis
during the duration of the study (Can defer assessment until end of allergy season for
seasonal allergies.);
6. has a history of ICU admission or intubation for asthma-related ventilatory failure in
adolescence (after approximately age 11) or adulthood;
7. is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV;
8. has clinically significant abnormalities in screening laboratory tests or ECG;
9. has significant nasal septal deviation, nasal polyps, or other nasal anatomical
abnormality;
Note: History of nasal corrective surgery is allowed if it occurred > 5 years prior to
the pre-trial (screening) visit and healed normally.
10. shares the same household or has intimate contact with an infant, a pregnant or
lactating woman, or an immunosuppressed individual;
11. has a history or current evidence of any upper or lower respiratory tract infection or
symptoms of such within 6 weeks of baseline assessment (Can defer assessment until
appropriate time has passed.);
12. had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
weeks prior to the pre-trial (screening) visit;
13. has participated in another investigational trial within 10 weeks prior to the pre-trial
(screening) visit. The 10 week window will be derived from the date of the last trial
medication and / or blood collection in a previous trial and/or AE related to trial drug
to the pre-trial/screening visit of the current trial;
14. is pregnant or is a nursing mother;
15. is unable to refrain from or anticipates the use of prescription and/or non-prescription
medications** or herbal remedies (such as St. John*s Wort [Hypericum perforatum])
beginning 2 weeks (o

Study & Design

• Study Type: Interventional
• Study Design: Not specified