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

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 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model.

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 Overview

• Status: Completed
• Conditions: RSV Infection
• Intervention / Treatment: Drug: EDP-938 Dose 1; Drug: EDP-938 Dose 2; Drug: Placebo; Drug: EDP-938 Dose 3; Drug: EDP-938 Dose 4

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • hVIVO Services Limited (hVIVO)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP-938 Arm A; Subjects will take EDP-938 Dose 1 oral suspension for 5 days	Drug: EDP-938 Dose 1; Oral suspension for 5 days
Experimental: EDP-938 Arm B; Subjects will take EDP-938 Dose 2 oral suspension for 5 days	Drug: EDP-938 Dose 2; Oral suspension for 5 days
Placebo Comparator: Placebo Arm C; Subjects will take matching placebo oral suspension for 5 days	Drug: Placebo; Oral suspension for 5 days
Experimental: EDP-938 Arm D; Subjects will take EDP-938 Dose 3 oral suspension for 5 days	Drug: EDP-938 Dose 3; Oral suspension for 5 days
Experimental: EDP-938 Arm E; Subjects will take EDP-938 Dose 4 oral suspension for 5 days	Drug: EDP-938 Dose 4; Oral suspension for 5 days
Placebo Comparator: Placebo Arm F; Subjects will take matching placebo oral suspension for 5 days	Drug: Placebo; Oral suspension for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Twice daily on Day 2 through Day 11 and once on Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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	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.	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.	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.	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.	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.	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).	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).	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.	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.	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.	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.	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		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.	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		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.	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.	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.	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.	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.	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.	Day 2 to Day 18

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc
• Collaborators: hVIVO Services Limited

Publications and helpful links

General Publications

• Ahmad A, Eze K, Noulin N, Horvathova V, Murray B, Baillet M, Grey L, Mori J, Adda N. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med. 2022 Feb 17;386(7):655-666. doi: 10.1056/NEJMoa2108903.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): October 18, 2019

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: RSV; antiviral; challenge study; RSV-A Memphis 37b
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: EDP 938-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No