Safety, Pharmacokinetics,and Antiviral Activity of RV299 Against Respiratory Syncytical Virus (RSV)

Study Overview
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Brief Summary
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The purpose of the study is to learn about the safety, pharmacokinetics and antiviral activity of the study medicine (RV299) for the potential treatment of respiratory syncytial virus (RSV). RSV is a highly contagious virus that can lead to serious lung infections in patients with reduced ability to fight infection. Most vulnerable populations include babies, the elderly and patients that have received a bone marrow transplant.

Detailed Description
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This study is seeking healthy participants who are: Healthy adult male and female participants aged between 18 to 55 years, with a total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35kg/m2 and who have been screened to be sero-suitable for infection with the RSV-A Memphis 37b virus challenge virus. A total of 80 participants is planned: 40 participants on RV299 and 40 participants on placebo. The study is divided into 3 phases: Screening phase: from Day -90 to Day-3 pre-human viral challenge (HVC). Inpatient phase: Participants will be resident in the quarantine unit for approximately 15 days (from Day -2 to Day 12). Post RSV-A Memphis 37b virus inoculation on Day 0, participants will be randomized to receive RV299 or matched placebo. Administration of RV299 or placebo will be twice daily ( 12 hours interval) for 5 consecutive days and will start on confirmation of RSV infection. Outpatient phase: Day 28 (±3 days)

Official Title
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A RANDOMISED, PHASE 1B, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND ANTIVIRAL ACTIVITY OF RV299 AGAINST RESPIRATORY SYNCYTIAL VIRUS IN THE VIRAL CHALLENGE MODEL

Conditions
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Respiratory Syncytial Virus (RSV)

Intervention / Treatment
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* Drug: RV299
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Total body weight >= 50 kg and body mass index (BMI) >=18 kg/m2 and <=35 kg/m2 in good health with no history, or current evidence of clinically significant medical condition of laboratory, ECG or vital sign abnormality Sero suitable for challenge virus Exclusion Criteria: History of or currently active symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to first study visit Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological (including immunosuppression),metabolic, urological, renal, neurological, or psychiatric disease and/or other major disease females who are breastfeeding or have been pregnant within 6 months prior to the study or have a positive pregnancy test Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction Any significant abnormality altering the anatomy of the nose in a substantial way Any clinically significant history of epistaxis (large nosebleeds) Any nasal or sinus surgery within 3 months of first study visit Evidence of vaccinations within 4 weeks of Day 0 Receipt of blood or blood products, or loss of 550 mL or more blood within last 3 months Receipt of 3 or more investigational drug within last 12 months Prior inoculation with a virus from the same virus-family as the challenge Prior participation in another HVC study with a respiratory virus in last 3 months Use or anticipated use during the conduct of the study of protocol specified concomitant medications Systemic antiviral administration within 4 weeks of viral challenge Confirmed positive test for drugs of abuse History or presence of alcohol addiction, or excessive use of alcohol A forced expiratory volume in 1 second (FEV1) <80% Positive HIV, hepatitis B virus, or hepatitis C virus test Presence of fever upto 2 days prior to Day 0.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>spray-dried dispersion (SDD) for Oral Suspension | Drug: RV299<br>* Oral Suspension<br>|
| Placebo Comparator: Placebo<br>spray-dried dispersion (SDD) for Oral Suspension | Drug: Placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) for RSV viral load measured by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) in nasal washes in participants inoculated with RSV-A Memphis 37b |  | Day 1 to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak viral load of RSV as defined by the maximum viral load determined by qRT-PCR measured in nasal samples |  | Day 1 to Day 12 | 
| Time (days) to confirmed negative test by qRT-PCR measurements in nasal samples |  | Day 1 to Day 12 | 
| Time (days) to peak qRT-PCR in nasal samples |  | Day 1 to Day 12 | 
| Area under the viral load-time curve (VL-AUC) of RSV challenge as determined by viral culture on nasal samples |  | Day 1 to Day 12 | 
| Peak viral load of RSV as defined by maximum viral load determined by viral culture measurements in nasal samples |  | Day 1 to Day 12 | 
| Time (days) to confirmed negative test by viral culture measurements in nasal samples |  | Day 1 to Day 12 | 
| Area under the curve over time of total clinical symptoms (TSS-AUC) | TSS measured from 10 symptoms collected 3 times daily | Day 1 to Day 12 | 
| TSS-AUC change from baseline (TSS-AUC-CFB) | TSS measured from 10 symptoms collected 3 times daily | Day 1 to Day 12 | 
| Peak total clinical symptoms (TSS) | TSS measured from 10 symptoms collected 3 times daily | Day 1 to Day 12 | 
| Individual maximum daily sum of symptom score |  | Day 1 to Day 12 | 
| Time (days) to symptom resolution |  | Day 1 to Day 10 | 
| Total weight of mucus produced |  | Day 1 to Day 12 | 
| Total number of tissues used |  | Day 1 to Day 12 | 
| Incidence of AEs |  | Day 1 to Day 12 | 
| Incidence of SAEs |  | Day 1 to Day 12 | 
| Incidence of AEs related to viral challenge |  | Day 0 to Day 28 | 
| Incidence of SAEs related to viral challenge |  | Day 0 to Day 28 | 
| Use of concomitant medications from viral challenge |  | Day 0 to Day 28 | 
| Time to maximum plasma concentration (tmax) |  | Day 1 to Day 12 | 
| Terminal half life (t1/2) |  | Day 1 to Day 12 | 
| Area under the plasma concentration-time curve (AUCtau) |  | Time 0 hours after Dose 1 to 96 hours after Dose 10 | 
| Area under the plasma concentration-time curve (AUC24) |  | Time 0 to Time 24 hours | 
| Area under the plasma concentration-time curve (AUCinfinity) |  | Time 0 hours after Dose 1 to 96 hours after Dose 10 | 
| Maximum concentration (Cmax) |  | Time 0 hours after Dose 1 to 96 hours after Dose 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-viral, Challenge