A Phase 2a Study to Evaluate EDP-938 in the Virus Challenge Model

Phase 2

Completed

Conditions: RSV Infection

Interventions: Drug: EDP-938 Dose 3
Drug: Placebo
Drug: EDP-938 Dose 2
Drug: EDP-938 Dose 4
Drug: EDP-938 Dose 1

Registration Number: NCT03691623

Lead Sponsor: Enanta Pharmaceuticals, Inc

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 179

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/m^2 and ≤ 30kg/m^2

Exclusion Criteria

Pregnant or nursing females
Acute or chronic medical illness
Abnormal lung function
Positive for human immunodeficiency virus (HIV), active hepatitis A, 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-938 Arm D	EDP-938 Dose 3	Subjects will take EDP-938 Dose 3 oral suspension for 5 days
Placebo Arm F	Placebo	Subjects will take matching placebo oral suspension for 5 days
EDP-938 Arm B	EDP-938 Dose 2	Subjects will take EDP-938 Dose 2 oral suspension for 5 days
EDP-938 Arm E	EDP-938 Dose 4	Subjects will take EDP-938 Dose 4 oral suspension for 5 days
Placebo Arm C	Placebo	Subjects will take matching placebo oral suspension for 5 days
EDP-938 Arm A	EDP-938 Dose 1	Subjects will take EDP-938 Dose 1 oral suspension for 5 days

Primary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load	Twice daily on Day 2 through Day 11 and once on Day 12	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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) of Total Symptom Score	Three times daily on Day 0 to Day 11, once on Day 12	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 to Resolution From Peak Total Symptom Score	Day 2 to Day 12	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.
Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites	Day 2 and Day 7; 24 hours post-dose	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time to Resolution From Peak Viral Load	Day 2 to Day 12	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 to Cessation of Virus Detection	Day 2 to Day 12	Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Time to Peak Total Symptom Score	Day 2 to Day 12	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.
Total Weight of Nasal Mucus Produced	Day 2 to Day 12	Measured via weighed paper tissues and reported as a mean total across all study days.
Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938	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	Day 2 to Day 18	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.
Peak Total Symptom Score	Day 2 to Day 12	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
Peak Viral Load	Day 2 to Day 12	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 to Peak Viral Load	Day 2 to Day 12	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.
Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Day 2 to Day 28	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.
Total Symptom Score	Day 2 to Day 9	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
Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Volume of Distribution at Steady State (Vss/F) of EDP-938	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	Day 2 and Day 7; 12 hours post-dose	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
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	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	The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC	Day 2 to Day 18	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.