A randomised, Phase 2a, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics and antiviral activity of multiple doses of orally administered EDP-938 in healthy subjects infected with RSV-A Memphis 37b. This study is designed to compare the antiviral effect of EDP-938 compared to a placebo control in the respiratory syncytial virus challenge model.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
179
Oral suspension for 5 days
Oral suspension for 5 days
Oral suspension for 5 days
hVIVO Services Limited (hVIVO)
London, United Kingdom
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
Measured in nasal washes by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in participants inoculated with respiratory syncytial virus-A (RSV-A) Memphis 37b.
Time frame: Twice daily on Day 2 through Day 11 and once on Day 12
Area Under the Curve (AUC) of Total Symptom Score
Total symptom scores (from the 10-item Diary Card) were used to calculate the AUC. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise (Tiredness) * Cough * Shortness of breath * Headache * Muscle/ joint ache/ stiffness Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). Data presented is hours x score.
Time frame: Three times daily on Day 0 to Day 11, once on Day 12
Peak Total Symptom Score
Peak total symptom score was defined as the highest total symptom score between first dose of study drug and Day 12. Values presented are a sum of individual symptom scores, with a potential range of 0 (best) to 30 (worst). Total symptom scores at the time of the first dose of study drug can be before or after dosing. Measured by the 10-item Diary Card. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise (Tiredness) * Cough * Shortness of breath * Headache * Muscle/ joint ache/ stiffness
Time frame: Day 2 to Day 12
Total Symptom Score
Measured by the 10-item Diary Card. Each individual symptom score was graded on a scale of 0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does not prevent participation in activities and Grade 3 is bothersome and interferes with activities. Total symptom score is the sum of individual symptom scores with a potential range of 0 (best) to 30 (worst). * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise (Tiredness) * Cough * Shortness of breath * Headache * Muscle/ joint ache/ stiffness
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Oral suspension for 5 days
Oral suspension for 5 days
Oral suspension for 5 days
Time frame: Day 2 to Day 9
Time to Peak Total Symptom Score
Time to peak total symptom score was defined as the time in days to the highest total symptom score between first dose of study drug and Day 12. Total symptom scores at the time of the first dose of study drug can be before or after dosing.
Time frame: Day 2 to Day 12
Time to Resolution From Peak Total Symptom Score
Time to resolution from peak total symptom score was defined as the time in days from the highest total symptom score (between first dose of study drug and Day 12) until the start of the first 24-hour symptom-free period (after the highest total symptom score). Total symptom scores at the time of the first dose of study drug can be before or after dosing.
Time frame: Day 2 to Day 12
Total Weight of Nasal Mucus Produced
Measured via weighed paper tissues and reported as a mean total across all study days.
Time frame: Day 2 to Day 12
Peak Viral Load
Peak viral load was defined as the highest quantitative reverse transcription polymerase chain reaction (RT-qPCR) viral load value between first dose of study drug and Day 12. Measured by nasal wash RT-qPCR.
Time frame: Day 2 to Day 12
Time to Peak Viral Load
Time to peak viral load was defined as the time to the highest quantitative reverse transcription polymerase chain reaction (RT-qPCR) viral load value between first dose of study drug and Day 12. Measured by nasal wash RT-qPCR.
Time frame: Day 2 to Day 12
Time to Resolution From Peak Viral Load
Time to resolution from peak viral load was defined as the time from peak until first confirmed undetectable assessment between first dose of study drug and Day 12. Measured by by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Time frame: Day 2 to Day 12
Time to Cessation of Virus Detection
Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Time frame: Day 2 to Day 12
Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any untoward medical occurrence in participants that happened after study drug administration. Any clinically significant physical examinations, vital signs, clinical laboratory tests (including biochemistry, hematology, coagulation \[if required\], cardiac enzymes and urine analysis), 12-lead electrocardiograms (ECGs) and spirometry results were recorded as adverse events.
Time frame: Day 2 to Day 28
Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (λz) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Volume of Distribution at Steady State (Vss/F) of EDP-938
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 7; 12 hours post-dose
Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 7; 24 hours post-dose
Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2: pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose; and Day 7: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time frame: Day 2 and Day 6: Pre-dose, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Day 7 only: 15, 24, 30, 36, 48, 60, and 72 hours post-dose
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC
The overall criteria to define correlation was based on identifying a PK AUC associated with a less favorable viral load AUC i.e. a low PK AUC and a high viral load AUC indicated a correlation.
Time frame: Day 2 to Day 18
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC
The overall criteria to define correlation was based on identifying a PK AUC associated with a less favorable TSS AUC, i.e. a low PK AUC and a high TSS AUC indicated a correlation.
Time frame: Day 2 to Day 18