asthma dyspnea respiratory disease
Conditions
Interventions
There are no pharmacologic treatments being studied. This study involves a
nasal rhinovirus challenge in both Parts 1 & 2 of the study.
In Parts 1 and 2, the rhinovirus challenge will occur on Day 0
10 TCID50 will be the starting dose in
Part 1.
The remaining doses span the range (up to 10,000 TCID50) of published
experience with rhinovirus 16 and merit testing to verify similarity of potency
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study Part 1 (1) Objective: To establish the safety and tolerability of nasal challenge with RV16UB in healthy subjects. Hypothesis: In healthy subjects, single nasal challenge with RV16UB is sufficiently safe and well tolerated to permit its evaluation in asthmatic subjects. (2) Objective: To establish the safety and tolerability of nasal challenge with RV16UB in mild to moderate asthmatics on inhaled corticosteroids (ICS). Hypothesis: In mild to moderate asthmatics taking ICS, single nasal challenge with RV16UB is sufficiently safe and well tolerated to permit its use in Part 2. (3) Objective: To select a dose of RV16UB that induces symptoms at days 1-7 in most asthmatics following nasal challenge Hypothesis: At least one of the four challenge doses of RV16UB will be associated with a) significant elevation above baseline of mean maximum post-challenge Jackson cold symptom scores (CSS), and b) at least three (3) members in the dose group having diary-based CSS * 3 for two days in a row, and c) at least four (4) members in the dose group demonstrating at least 1000 copies /mL of viral RNA in nasal lavage fluid as measured by qRT-PCR. (4) Objective: To determine whether mild to moderate asthmatics taking LABA are appropriate participants in nasal challenge studies with RV16UB. Hypothesis: I) In mild to moderate asthmatics taking ICS and LABA, single nasal challenge with RV16UB is sufficiently safe and well tolerated to permit its use in Part 2. II) Cohorts of LABA-taking asthmatics demonstrate the similar nasal and viral shedding characteristics as asthmatics not taking LABA. At least one of the four challenge doses of RV16UB will be associated with the following in a cohort of LABA-taking asthmatics: a) significant elevation above baseline of mean maximum post-challenge Jackson cold symptom scores (CSS), and b) at least three (3) members in the dose group having diary-based CSS * 3 for two days in a row, and c) at least four (4) mem | — |
Secondary
| Measure | Time frame |
|---|---|
| 3.2 Secondary Objective(s) & Hypothesis(es) Study Part 2 (1) Objective: To estimate the CFB in FEV1 (maximum drop), and TWA3-10 in Asthma Control Diary (ACD) score. Hypotheses: The mean CFBs in maximum drop FEV1, and increase in TWA3-10 ACD are different from zero. (2) Objective: To estimate the within-subject Spearman correlations between maximum cold symptom score, TWA0-14 nasal virus titer (PCR), and each of TWA1-7 and max drop FEV1, maximum diary-based ACD and TWA3-10 of diary-based ACD. Hypotheses: The within-subject Spearman correlations between maximum CSS, TWA0-14 nasal virus titer, and each of TWA1-7 FEV1, maximum drop FEV1, and TWA3-10 ACD will all be different from zero in the expected directions. (3) Objective: To describe the course of virus shedding (PCR-quantitated) following challenge. (4) Objective: To describe the virus-induced changes in high-dimensionality clinical and biological phenotypes (*handprints*) of mild-moderate asthmatics using the UBIOPRED multiscale systems medicine approach (*handprint analysis*). This description includes all outcomes listed under primary, secondary and exploratory objectives. | — |
Countries
Netherlands
Outcome results
None listed