Human Respiratory Syncytial Virus (RSV) MedDRA version: 20.0 Level: LLT Classification code 10070358 Term: Human respiratory syncytial virus test positive System Organ Class: 100000109842
Conditions
Interventions
Product Code: PC786
Pharmaceutical Form: Powder for nebuliser suspension
INN or Proposed INN: N/A
Current Sponsor code: PC786
Concentrat
Sponsors
Pulmocide Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be male or female, aged between 18 and 55 years inclusive (at the time of consent) who fit one of the following criteria Women of childbearing potential who have a documented menstrual period within 28 days prior to first dose. Women of non-childbearing potential defined as being amenorrhoeic for >12 months with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms). Men who are willing and able to use one of the contraception methods described in the protocol, from the time of the date of Viral Challenge, until 90 days after receipt of the final dose of study medication. 2. Sero-suitable to the challenge virus 3. In good health with no history of major medical conditions that will interfere with subject safety, as defined by medical history, physical examination, and routine laboratory tests and determined by the Investigator at a screening evaluation. The following conditions are deemed acceptable: • Subjects with a history of rhinitis, currently inactive (within the last 30 days and not required nasal corticosteroids in this time) or with ongoing mild rhinitis may be included at the PI’s discretion • Subjects with clinically mild atopic eczema/atopic dermatitis and clinically mild psoriasis may be included at the Investigator's discretion (e.g., use of low/mild potency regular topical steroids is acceptable. Eczema in the cubital fossa and/or use of medium to high potency dermal corticosteroids are exclusions) • Subjects with a physician diagnosed underactive thyroid who have been controlled on treatment for at least 6 months with evidence of a normal thyroid function test (TFT) can be included at the discretion of the PI • Subjects reporting physician diagnosed migraine can be included as long as there are no associated neurological symptoms such as hemiplegia or visual loss • Subjects with physician diagnosed mild Irritable Bowel Syndrome (IBS) not requiring regular treatment can be included at the discretion of the PI • Subjects who have experienced no more than one mild (mild is defined as having been treated with bronchodilators only) episode of wheeze after the age of 12, may be included at the Investigator’s discretion, providing the episode lasted no more than 2 weeks, and ended more than 1 year ago. A history of childhood asthma up to and including the age of 12 years is acceptable provided the subject is asymptomatic without treatment. 4. A total body weight = 50 kg and Body Mass Index (BMI) = 18 kg/m2 and = 30kg/m2 5. Females must have a negative serum ß human chorionic gonadotropin (ß-hCG) at screening and a negative urinary pregnancy test at Day –2 or Day –1. 6. Subject must be willing and able to adhere to the restrictions and prohibitions required by this protocol. 7. An informed consent document signed and dated by the subject and the Investigator. 8. Subjects will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening. 9. Serosuitable to the challenge virus, the serology result obtained suggests that the subject is appropriately sensitive to RSV (RSV-A Memphis 37b virus). Are the t
Exclusion criteria
Exclusion criteria: 1. Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge 2. Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalised due to epistaxis on any previous occasion 3. Any nasal or sinus surgery within six months of inoculation 4. Subjects who have smoked = 10 pack years at any time 5. Subjects who have smoked 37.5oC on Day -2, Day -1, and/or pre-Challenge on Day 0 15. Evidence of vaccinations within the 4 weeks prior
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antiviral effect of inhaled PC786 compared to placebo in healthy adults who have received a clinical challenge strain of RSV (RSV-A Memphis 37b virus) inoculated via the intranasal route;Primary end point(s): The area under the curve (AUC 0-t) for RSV viral load measured in nasal washes by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in subjects with confirmed infection with RSV-A Memphis 37b; Secondary Objective: • To assess the safety and tolerability of repeat inhaled doses of PC786 in healthy adults inoculated with RSV-A Memphis 37b virus • To obtain estimates of derived systemic pharmacokinetic parameters of PC786 and the potential circulating metabolite(s), if detectable, following the initial and repeat doses of inhaled PC786 for 5 days • To determine the nasal concentrations of PC786 following facemask delivery • To compare the effect of inhaled PC786 with that of placebo on mucus production in healthy adults inoculated with RSV-A Memphis 37b virus • To compare the effect of inhaled PC786 with that of placebo on RSV symptoms in healthy adults inoculated with RSV-A Memphis 37b virus ; Timepoint(s) of evaluation of this end point: AUC 0-t for RSV viral load from nasal washes (NW): Screening (S); Admit to Quarantine (A); Days 2-11, twice daily (12 hours between assessments), Days 12 and 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety data including, but not limited to, tabulation of adverse events (AEs), physical examinations, spirometry, vital signs, 12- lead ECGs and clinical laboratory results • Derived pharmacokinetic parameters of PC786 and the potential circulating metabolite(s) if detectable, including AUC, Cmax, t1/2, tmax, accumulation ratio and metabolite(s) to parent AUC ratio, following repeat doses • PC786 concentration determination in mucosal lining fluid (MLF) collected using synthetic absorptive matrix (SAM) • Reduction in total weight of mucus produced post viral inoculation through to last administration of PC786 and until Day 12 post inoculation • Relationship between various PK parameters (e.g., Cmax, Cmin, and AUC) and antiviral endpoints (e.g., viral load AUC, duration of shedding, symptom scores) • Additional antiviral endpoints (as determined by RT-qPCR of nasal wash) including: - change in viral load from baseline (prior to first dose of PC786) to Day 12 change in AUC0-t over different time periods - time to non-detectability of virus from commencement of study medication - peak viral load and time to peak viral load from baseline (prior to first dose of PC786) - proportion of subjects with detectable virus by time following commencement of study medication • Change in total RSV-A symptoms after challenge until Day 12 post inoculation (using a composite of 10 self-reported symptoms on the symptom diary card (SDC)) analysis includes, but not limited to, AUC total symptoms from baseline (prior to first dose of PC786) to Day 12 ; Timepoint(s) of evaluation of this end point: AEs: Screening (S); Admit to Quarantine (A); Day (D) -2-12; D28 Physical Exam: S; A; D0 (pre & post Viral Challenge (VC)); D1-12; D28 Spirometry: S; A; | — |
Countries
United Kingdom
Contacts
Public ContactDirector of Clinical Development
Pulmocide Ltd
Outcome results
None listed