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

Pfizer82 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Respiratory Syncytial Virus (RSV)

Interventions

RV299DRUG

Oral Suspension

PlaceboDRUG

matching placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Pfizer

London, United Kingdom

Outcomes

Primary Outcomes

Area Under the Curve (AUC) for RSV-A Memphis 37b Viral Load Determined by Quantitative Real Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR)

Area under the curve (AUC) for RSV viral load measured in nasal washes by qRT-PCR in participants inoculated with RSV-A Memphis 37b, from initial administration of IMP up to the morning of Day 12 (Quarantine discharge) was presented in this outcome measure.

Time frame: From initial administration of IMP up to the morning of quarantine discharge (up to Day 12)

Secondary Outcomes

Peak Viral Load of RSV Determined by qRT-PCR

Peak viral load of RSV as defined by the maximum viral load determined by qRT-PCR measurements in nasal samples starting from initial administration of IMP up to planned discharge from quarantine was reported in this outcome measure.

Time frame: From initial administration of IMP up to planned discharge from quarantine (Up to Day 12)

Time to Confirmed Negative Test by qRT-PCR Measurement Starting From Initial Administration of Investigational Medicinal Product (IMP) to First Confirmed Undetectable Assessment After Peak Measure

The time from the first administration of IMP to the first confirmed negative qRT-PCR test after the peak qRT-PCR measurement was calculated as: Date and time of first confirmed negative test after peak qRT-PCR measurement minus Date and time of first IMP administration. A negative test was defined as two consecutive 'Not Detected' results in the qRT-PCR test. The peak qRT-PCR was defined as the highest viral load value obtained by a participant after their first administration of IMP. Participants without a confirmed undetectable assessment after their peak, were censored at their last detected qRT-PCR assessment.

Time frame: From first administration of IMP to the first confirmed negative qRT-PCR test or censoring date (up to Day 12)

Time to Confirmed Negative Test by qRT-PCR Measurement Starting From Peak qRT-PCR After Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The time from the peak qRT-PCR measurement after administration of IMP to the first confirmed negative qRT-PCR test was calculated as (Date and time of first confirmed negative test after peak qRT-PCR measurement minus Date and time of peak qRT-PCR measurement). A negative test was defined as two consecutive 'Not Detected' results in the qRT-PCR test. The peak qRT-PCR was defined as the highest viral load value obtained by a participant after their first administration of IMP. Participants without a confirmed undetectable assessment after their peak, were censored at their last detected qRT-PCR assessment.

Time frame: From peak qRT-PCR measurement to the first confirmed negative qRT-PCR test or censoring date (up to Day 12)

Time to Peak qRT-PCR Starting From Initial Administration of IMP

The time to the peak qRT-PCR measurement starting from the initial administration of IMP was calculated as: Date and time of peak qRT-PCR measurement minus Date and time of first IMP administration. The peak qRT-PCR was defined as the highest viral load value obtained by a participant after their first administration of IMP.

Time frame: From first administration of IMP to peak qRT-PCR measurement (up to Day 12)

Area Under the Viral Load-Time Curve (VL-AUC) for RSV-A Memphis 37b Determined by Viral Culture

Area under the viral load-time curve (VL-AUC) of RSV challenge virus as determined by viral culture on nasal samples, starting at initial administration of IMP up to planned discharge from quarantine was reported in this outcome measure.

Time frame: From initial administration of IMP up to planned discharge from quarantine (up to Day 12)

Peak Viral Load of RSV Determined by Viral Culture

Peak viral load of RSV as defined by the maximum viral load determined by viral culture measurements in nasal samples starting from initial administration of IMP up to planned discharge from quarantine was reported in this outcome measure.

Time frame: From initial administration of IMP up to planned discharge from quarantine (up to Day 12)

Time to Confirmed Negative Test by Viral Culture Measurement Starting From at Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure

Time to confirmed negative test by viral culture measurements in nasal samples from initial administration of IMP up to first confirmed negative viral culture measurement after the peak viral culture measurement was calculated as: Date and time of first confirmed negative test after peak viral culture measurement minus Date and time of first IMP administration. A negative test was defined as two consecutive 'Not Detected' results in the viral culture test. The peak viral culture measurement was defined as the highest viral load value obtained by a participant after their first administration of IMP. Participants who did not have a confirmed undetectable assessment after their peak viral culture measurement after first administration of IMP were censored at their last detectable assessment.

Time frame: From initial administration of IMP up to first confirmed undetectable assessment or censoring date (up to Day 12)

Time to Confirmed Negative Test by Viral Culture Measurement Starting From Peak Viral Culture After Initial Administration of IMP to First Confirmed Undetectable Assessment After Peak Measure

The time from the peak viral culture measurement after administration of IMP to the first confirmed negative viral culture measurement was calculated in days as: Date of and time first confirmed negative test minus Date and time of peak qRT-PCR measurement. A negative test was defined as two consecutive 'Not Detected' results in the viral culture test. The peak viral culture measurement was defined as the highest viral load value obtained by a participant after their first administration of IMP. Participants who did not have a confirmed undetectable assessment after their peak viral culture measurement after first administration of IMP were censored at their last detectable assessment.

Time frame: From peak qRT-PCR measurement to first confirmed undetectable assessment or censoring date (up to Day 12)

Area Under the Curve Over Time of Total Clinical Symptoms as Measured From 10 Symptoms Within the Graded Symptom Scoring System

Area under the Curve over Time of Total Clinical Symptoms (TSS-AUC) as measured from 10 symptoms within Graded Symptom Scoring System Collected 3 Times Daily Starting at Initial Administration up to Planned Discharge from Quarantine. TSS (from 10 items of the 13-item symptom diary card) was used to calculate the AUC, from the assessment nearest to the time of the first administration of IMP until Day 12. Following types of symptoms were recorded on symptom diary cards: Upper Respiratory Tract (URT): runny nose, stuffy nose, sore throat, sneezing, earache; Lower Respiratory Tract (LRT): cough, shortness of breath; Systemic: headache, malaise, muscle/joint ache/stiffness. Each symptom was recorded on a grading scale of 0 to 3 (or 0 to 4 for the Shortness of Breath symptom), higher scores = greater severity of symptoms. Total symptom score was calculated as sum of the 10 observed symptom grade values and ranged from 0 to 31, where higher scores indicated more severe symptoms.

Time frame: From initial administration of IMP (before or after administration) up to planned discharge from quarantine (up to Day 12)

Area Under the Curve Over Time of Total Clinical Symptoms Change From Baseline (TSS-AUC-CFB) as Measured From 10 Symptoms Within the Graded Symptom Scoring System

Area under the curve over time of total clinical symptoms change from baseline (TSS-AUC-CFB) as measured from 10 symptoms within the graded symptom scoring system collected 3 times daily starting at initial administration of IMP up to planned discharge from quarantine (Day 12, am). The following types of symptoms were recorded: Upper Respiratory Tract (URT): runny nose, stuffy nose, sore throat, sneezing, earache; Lower Respiratory Tract (LRT): cough, shortness of breath; Systemic: headache, malaise, muscle/joint ache/stiffness. Each symptom was recorded on a grading scale of 0 to 3 (or 0 to 4 for the Shortness of Breath symptom), where higher scores indicated greater severity of symptoms. TSS was calculated as sum of the 10 observed symptom grade values and ranged from 0 to 31, where higher scores indicated more severe symptoms. The AUC calculation was based on the available non-missing calculated total symptom scores between the start and end of the defined AUC time.

Time frame: Baseline (assessment nearest to the time of the first administration of IMP) up to Day 12

Overall Peak Total Clinical Symptoms (TSS) Score

Peak total clinical symptoms (TSS) as measured from 10 symptoms within the graded symptom scoring system collected 3 times daily starting from initial administration of IMP up to planned discharge from quarantine. The following types of symptoms were recorded: Upper Respiratory Tract (URT): runny nose, stuffy nose, sore throat, sneezing, earache; Lower Respiratory Tract (LRT): cough, shortness of breath; Systemic: headache, malaise, muscle/joint ache/stiffness. Each symptom was recorded on a grading scale of 0 to 3 (or 0 to 4 for the Shortness of Breath symptom), where higher scores indicated greater severity of symptoms. The total symptom score was calculated as sum of the 10 observed symptom grade values and ranged from 0 to 31, where higher scores indicated more severe symptoms. The overall peak score was defined as the highest scoring symptom diary card observed from the first administration of IMP until quarantine discharge.

Time frame: From initial administration of IMP (before or after administration) up to planned discharge from quarantine (up to Day 12)

Individual Maximum Daily Peak Symptom Score

Individual maximum daily sum of symptom score from initial administration of IMP up to planned discharge from quarantine. The following types of symptoms were recorded: Upper Respiratory Tract (URT): runny nose, stuffy nose, sore throat, sneezing, earache; Lower Respiratory Tract (LRT): cough, shortness of breath; Systemic: headache, malaise, muscle/joint ache/stiffness. Each symptom was recorded on a grading scale of 0 to 3 (or 0 to 4 for the Shortness of Breath symptom), where higher scores indicated greater severity of symptoms. The total symptom score was calculated as sum of the 10 observed symptom grade values and ranged from 0 to 31, where higher scores indicated more severe symptoms. The highest total symptom score recorded on each day, across the three assessments was reported in this outcome measure. The peak daily score was defined as the highest scoring symptom diary card observed on each day from the first administration of IMP until quarantine discharge.

Time frame: Day 0, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9 (days relative to first administration of IMP)

Time to Symptom Resolution Starting at Initial Administration of IMP to 24 Hours Symptom Free

Symptom resolution was defined as a participant scoring 0 for the total symptom score for a 24-hour period (e.g., a minimum of three consecutive symptom diary cards, each with a score of 0) after their peak symptom score. The time from the assessment at the time of the first administration of IMP until symptom resolution was calculated as: Date and time of symptom resolution minus Date and time of assessment at IMP administration. If the peak symptom score occurred on more than one day then the first occurrence was selected. Participants who did not record 24 hours symptom free after their highest total symptom score during the quarantine period were censored at their last assessment.

Time frame: From first administration of IMP until time of symptom resolution or censoring date (up to Day 12)

Time to Symptom Resolution Starting at Peak Symptoms After Initial Administration to 24 Hours Symptom Free

Symptom resolution was defined as a participant scoring 0 for the total symptom score for a 24-hour period (e.g., a minimum of three consecutive symptom diary cards, each with a score of 0) after their peak symptom score. The time from the highest total symptom score following administration of IMP until symptom resolution was calculated as: Date and time of symptom resolution minus Date and time of highest total symptom score. If the peak symptom score occurred on more than one day then the first occurrence was selected. Participants who did not record 24 hours symptom free after their highest total symptom score during the quarantine period were censored at their last assessment.

Time frame: From time of highest total symptom score until time of symptom resolution or censoring date (up to Day 12)

Time to Peak Symptom Score From Initial Administration of IMP

Time to peak as measured from 10 symptoms within the graded daily symptom scoring system starting from initial administration of IMP to the time of peak daily symptom score. If the peak symptom score occurred on more than one day then the first occurrence was selected. Participants were censored at their last assessment if they did not record any symptoms during the quarantine period.

Time frame: From first dose of IMP until time of highest total symptom score or censoring date (Up to Day 12)

Total Weight of Mucus Produced Starting at Initial Administration of IMP up to Planned Discharge From Quarantine

Total weight of nasal mucus was calculated as the sum of mucus weights taken from the assessment at the time of the first administration of IMP (prior to or after dosing, depending on whether dosed in the morning or evening) to morning of Day 12 (Quarantine discharge).

Time frame: From first administration of IMP up to planned discharge from quarantine (up to Day 12)

Total Number of Tissues Used by Participants Starting At Initial Administration of IMP up to Planned Discharge From Quarantine

Total number of tissues was counted from the assessment at the time of the first dose of IMP (prior to or after dosing, depending on whether dosed in the morning or evening) to morning of Day 12 (Quarantine discharge).

Time frame: From first administration of IMP up to planned discharge from quarantine (up to Day 12)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event was defined as any untoward medical occurrence in clinical study participants administered a pharmaceutical product. An AE did not necessarily have a causal relationship with the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or important medical event.

Time frame: From first dose of IMP until end of follow-up visit (up to Day 28)

Number of Participants With AEs Related to Viral Challenge

An Adverse Event was defined as any untoward medical occurrence in clinical study participants administered a pharmaceutical product. An AE did not necessarily have a causal relationship with the study intervention. Number of participants with AEs possibly, probably or definitely related to viral challenge agents were reported by preferred terms in this outcome measure.

Time frame: From viral challenge on Day 0 up to end of follow-up (Day 28)

Number of Participants With Concomitant Medications

Number of participants with concomitant medications were reported in this outcome measure.

Time frame: From viral challenge on Day 0 up to end of follow-up (Day 28)

Time to Maximum Plasma Concentration (Tmax) for RV299

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12, 24, 36, 48, 60, 72, 84 and 96-hours post-dose 1 and dose 10

Terminal Half-Life (t1/2) for RV299

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12, 24, 36, 48, 60, 72, 84 and 96 hours post-dose 1 and dose 10

Maximum Observed Plasma Concentration for RV299

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12, 24, 36, 48, 60, 72, 84 and 96 hours post-dose 1 and dose 10

Area Under the Plasma Concentration-Time Curve From Time Zero to the End of the Dosing Interval for RV299

Area under the plasma concentration-time curve from time zero to the end of the dosing interval for RV299 where dosing interval=12 hours.

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12 hours post-dose 1 and dose 10

Area Under the Plasma Concentration-Time Curve Over the Last 24 Hours Dosing Interval for RV299

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12, 24 hours post-dose 1 and dose 10

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity for RV299 on Day 1

Time frame: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8,10, 12, 24, 36, 48, 60, 72, 84 and 96 hours post-dose 1