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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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RSV Infection

Intervention / Treatment
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* Drug: EDP-938 Dose 1
* Drug: EDP-938 Dose 2
* Drug: Placebo
* Drug: EDP-938 Dose 3
* Drug: EDP-938 Dose 4
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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challenge study, RSV, antiviral, RSV-A Memphis 37b