A randomized, Phase 2a, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics and antiviral activity of multiple doses of orally administered EDP-323 in healthy subjects infected with RSV-A Memphis 37b. This study is designed to assess the antiviral effect of EDP-323 compared to a placebo control in the respiratory syncytial virus challenge model.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
142
hVIVO Services Limited
London, United Kingdom
Quantitative Reverse Transcription-polymerase Chain Reaction (qRT-PCR): RSV Area Under the Viral Load-time Curve (VL-AUC)
Measured by qRT-PCR in nasal samples.
Time frame: Day 1 to Day 12
qRT-PCR: RSV Peak Viral Load (VLPEAK)
Measured by qRT-PCR in nasal samples.
Time frame: Day 1 to Day 12
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to RSV VLPEAK
Measured by qRT-PCR in nasal samples.
Time frame: Day 1 to Day 12
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to RSV Viral Load Negativity
The time from the assessment at the time of the first dose of IMP to qRT-viral load negativity was analyzed using the Kaplan-Meier method. Viral load negativity was reached at the first time when the viral load was undetectable (\< lower limit of detection \[LLOD\]) by qRT-PCR, after which no further detectable assessment appeared. Measured by qRT-PCR in nasal samples.
Time frame: Day 1 to Day 12
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to First Negative Slope of RSV Viral Load
Time to first negative slope = time of the timepoint after which there are two consecutive declines in viral load - time of the nearest viral load assessment to the first dose of IMP. Measured by qRT-PCR in nasal samples.
Time frame: Day 1 to Day 12
qRT-PCR: RSV Viral Load Clearance Rate - EDP-323 High Dose
Calculated as the slope of the RSV viral load over time from time of RSV VLPEAK to 1, 2, 3, and 4 days later. Estimates for fixed effects of a mixed linear model, modeling the viral load from peak up to the 4 following days, with time from VLPEAK, group and interaction between time and group as fixed effects and a random intercept within each participant. The model was a distinct analysis for the EDP-323 high dose and placebo groups where the estimates for both groups are model-dependent and impacted by the overall model. A negative slope indicated that the viral load decreased over time. Measured by qRT-PCR in nasal samples.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to Day 16
qRT-PCR: RSV Viral Load Clearance Rate - EDP-323 Low Dose
Calculated as the slope of the RSV viral load over time from time of RSV VLPEAK to 1, 2, 3, and 4 days later. Estimates for fixed effects of a mixed linear model, modeling the viral load from peak up to the 4 following days, with time from VLPEAK, group and interaction between time and group as fixed effects and a random intercept within each participant. The model was a distinct analysis for the EDP-323 low dose and placebo groups where the estimates for both groups are model-dependent and impacted by the overall model. A negative slope indicated that the viral load decreased over time. Measured by qRT-PCR in nasal samples.
Time frame: Up to Day 16
Viral Culture: RSV VL-AUC
Measured by viral culture (plaque assay) in nasal samples.
Time frame: Day 1 to Day 12
Viral Culture: RSV VLPEAK
Measured by viral culture (plaque assay) in nasal samples.
Time frame: Day 1 to Day 12
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to RSV VLPEAK
Measured by viral culture (plaque assay) in nasal samples.
Time frame: Day 1 to Day 12
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to RSV Viral Load Negativity
Measured by viral culture (plaque assay) in nasal samples.
Time frame: Day 1 to Day 12
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to First Negative Slope of RSV Viral Load
Measured by viral culture (plaque assay) in nasal samples.
Time frame: Day 1 to Day 12
Viral Culture: RSV Viral Load Clearance Rate
Calculated as the slope of the RSV viral load over time from time of RSV VLPEAK to 1, 2, 3, and 4 days later. Estimates for fixed effects of a mixed linear model, modeling the viral load from peak up to the 4 following days, with time from VLPEAK, group and interaction between time and group as fixed effects and a random intercept within each participant. A negative slope indicated that the viral load decreased over time. Measured by viral culture in nasal samples.
Time frame: Up to Day 16
Area Under the Total Symptom Score (TSS)-Time Curve (TSS-AUC)
An individual TSS (10-items) was derived at each assessment of the diary card as the sum of the scores given to the 10 following symptoms on that symptom score card, giving a score between 0 and 3: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise/Tiredness * Headache * Muscle and/or Joint Ache * Cough * Shortness of breath TSS ranged from 0 to 30 with higher TSS indicating a higher disease burden and thus a worse outcome. The calculation of the TSS-AUC was performed on the TSS measured 3 times a day using the trapezoidal summation rule based on actual time intervals in hours.
Time frame: Day 1 to Day 12
Peak TSS
Defined as the highest recorded value of TSS. An individual TSS (10-items) was derived at each assessment of the diary card as the sum of the scores given to the 10 following symptoms on that symptom score card, giving a score between 0 and 3: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise/Tiredness * Headache * Muscle and/or Joint Ache * Cough * Shortness of breath TSS ranged from 0 to 30 with higher TSS indicating a higher disease burden and thus a worse outcome.
Time frame: Day 1 to Day 12
Time to Peak TSS
Time to peak TSS = time of peak TSS - time of the nearest TSS assessment to the first dose of IMP. An individual TSS (10-items) was derived at each assessment of the diary card as the sum of the scores given to the 10 following symptoms on that symptom score card, giving a score between 0 and 3: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise/Tiredness * Headache * Muscle and/or Joint Ache * Cough * Shortness of breath TSS ranged from 0 to 30 with higher TSS indicating a higher disease burden and thus a worse outcome.
Time frame: Day 1 to Day 12
Time to Resolution From Peak TSS
Time to resolution from peak TSS = time of the first 24-hour symptom-free time point - time of peak TSS. An individual TSS (10-items) was derived at each assessment of the diary card as the sum of the scores given to the 10 following symptoms on that symptom score card, giving a score between 0 and 3: * Runny nose * Stuffy nose * Sneezing * Sore throat * Earache * Malaise/Tiredness * Headache * Muscle and/or Joint Ache * Cough * Shortness of breath TSS ranged from 0 to 30 with higher TSS indicating a higher disease burden and thus a worse outcome.
Time frame: Day 1 to Day 12
Total Weight of Nasal Discharge (Mucus) Produced
Each participant was given pre-weighed packets of paper tissues. Participants were asked to place single tissues used for nose blowing or sneezing into a specified collection bag (for that participant only).
Time frame: Day 1 to Day 12
Total Number of Tissues Used
Each participant was given pre-weighed packets of paper tissues. Participants were asked to place single tissues used for nose blowing or sneezing into a specified collection bag (for that participant only).
Time frame: Day 1 to Day 12
Maximum Plasma Concentration (Cmax)
Plasma pharmacokinetic (PK) parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, below the limit of quantification (BQL) values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: First Dose: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose) and Day 2 pre-dose; Last Dose: Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Time to Cmax (Tmax)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: First Dose: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose) and Day 2 pre-dose; Last Dose: Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Terminal Half-life (t1/2)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose), Day 2 pre-dose, Day 3 pre-dose, Day 4 pre-dose, Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Apparent Systemic Clearance at Steady-state (CLss/F)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose), Day 2 pre-dose, Day 3 pre-dose, Day 4 pre-dose, Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Terminal Elimination Rate Constant (λz)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose), Day 2 pre-dose, Day 3 pre-dose, Day 4 pre-dose, Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Apparent Volume of Distribution at Steady-state (Vss/F)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The plasma PK parameters were estimated from the concentration-time profiles. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose), Day 2 pre-dose, Day 3 pre-dose, Day 4 pre-dose, Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Plasma Concentration at 12 Hours (C12h) and 24 Hours (C24h)
In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: First Dose: Day 1, 12 and 24 hours post-dose; Last Dose: Day 5, 12 and 24 hours post-dose
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The AUCs were calculated using linear up/log down method. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: First Dose: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 15 hours post-dose) and Day 2 pre-dose; Last Dose: Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Plasma PK parameters for EDP-323 and metabolites (EP-038725 and EP-039082) were estimated using non-compartmental methods. The AUCs were calculated using linear up/log down method. In estimating the PK parameters, BQL values were set to zero. Actual sampling times, rather than scheduled sampling times, were used in all computations involving sampling times. If the actual time or dose time was missing, the scheduled time could be substituted in order to calculate the PK parameter. In case of an actual sampling time deviating by \>20% from the scheduled (nominal) time, this plasma concentration was excluded from descriptive statistics in the plasma concentration-time table.
Time frame: Last Dose: Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, and 72 hours post-dose)
Number of Participants With Adverse Events (AEs) up to Discharge
An AE was defined as any untoward medical occurrence in clinical study participants administered a pharmaceutical (investigational or non-investigation) product. An AE does not necessarily have a causal relationship with the study intervention. A serious AE (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 * Was an important medical event
Time frame: Day -2 to Day 12
Number of Participants With Treatment-emergent Adverse Events
An AE was defined as any untoward medical occurrence in clinical study participants administered a pharmaceutical (investigational or non-investigation) product. An AE does 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 * Was an important medical event
Time frame: Day 1 to Day 28