A Controlled Phase 2a Study to Evaluate the Efficacy of EDP-323 Against Respiratory Syncytial Virus Infection in a Virus Challenge Model

Phase 2

Completed

Conditions: RSV Infection

Interventions: Drug: EDP-323 Dose Regimen 1
Drug: EDP-323 Dose Regimen 2
Drug: Placebo

Registration Number: NCT06170242

Lead Sponsor: Enanta Pharmaceuticals, Inc

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 142

Inclusion Criteria

An informed consent document signed and dated by the subject.
Age 18 to 55 years, inclusive.
In good health with no history of major medical conditions.
A total body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 35kg/m2.

Exclusion Criteria

Pregnant or nursing females
Acute or chronic medical illness
History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract (URT or LRT) infection within 4 weeks prior to the first study visit.
Abnormal lung function
Positive for HIV, active hepatitis B or C test
Nose or nasopharynx abnormalities
Receipt of any investigational drug within 3 months prior to the planned date of viral challenge/first dose of study drug

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EDP-323 Arm A	EDP-323 Dose Regimen 1	Subjects will take EDP-323 Dose 1 orally for 5 days
EDP-323 Arm B	EDP-323 Dose Regimen 2	Subjects will take EDP-323 Dose 2 orally for 5 days
Placebo Arm C	Placebo	Subjects will take matching placebo orally for 5 days

Primary Outcome Measures

Name	Time	Method
Quantitative Reverse Transcription-polymerase Chain Reaction (qRT-PCR): RSV Area Under the Viral Load-time Curve (VL-AUC)	Day 1 to Day 12	Measured by qRT-PCR in nasal samples.

Secondary Outcome Measures

Name	Time	Method
qRT-PCR: RSV Peak Viral Load (VLPEAK)	Day 1 to Day 12	Measured by qRT-PCR in nasal samples.
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to RSV VLPEAK	Day 1 to Day 12	Measured by qRT-PCR in nasal samples.
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to RSV Viral Load Negativity	Day 1 to Day 12	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.
qRT-PCR: Time From the Assessment at the Time of the First Dose of IMP to First Negative Slope of RSV Viral Load	Day 1 to Day 12	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.
qRT-PCR: RSV Viral Load Clearance Rate - EDP-323 High Dose	Up to Day 16	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.
qRT-PCR: RSV Viral Load Clearance Rate - EDP-323 Low Dose	Up to Day 16	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.
Viral Culture: RSV VL-AUC	Day 1 to Day 12	Measured by viral culture (plaque assay) in nasal samples.
Viral Culture: RSV VLPEAK	Day 1 to Day 12	Measured by viral culture (plaque assay) in nasal samples.
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to RSV VLPEAK	Day 1 to Day 12	Measured by viral culture (plaque assay) in nasal samples.
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to RSV Viral Load Negativity	Day 1 to Day 12	Measured by viral culture (plaque assay) in nasal samples.
Viral Culture: Time From the Assessment at the Time of the First Dose of IMP to First Negative Slope of RSV Viral Load	Day 1 to Day 12	Measured by viral culture (plaque assay) in nasal samples.
Viral Culture: RSV Viral Load Clearance Rate	Up to Day 16	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.
Area Under the Total Symptom Score (TSS)-Time Curve (TSS-AUC)	Day 1 to Day 12	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.
Peak TSS	Day 1 to Day 12	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 to Peak TSS	Day 1 to Day 12	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 to Resolution From Peak TSS	Day 1 to Day 12	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.
Total Weight of Nasal Discharge (Mucus) Produced	Day 1 to Day 12	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).
Total Number of Tissues Used	Day 1 to Day 12	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).
Maximum Plasma Concentration (Cmax)	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)	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 to Cmax (Tmax)	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)	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.
Terminal Half-life (t1/2)	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 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.
Apparent Systemic Clearance at Steady-state (CLss/F)	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 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.
Terminal Elimination Rate Constant (λz)	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 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.
Apparent Volume of Distribution at Steady-state (Vss/F)	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 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.
Plasma Concentration at 12 Hours (C12h) and 24 Hours (C24h)	First Dose: Day 1, 12 and 24 hours post-dose; Last Dose: Day 5, 12 and 24 hours post-dose	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.
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last)	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)	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.
Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau)	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)	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.
Number of Participants With Adverse Events (AEs) up to Discharge	Day -2 to Day 12	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
Number of Participants With Treatment-emergent Adverse Events	Day 1 to Day 28	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