Back to resultsA Phase 2a Study to Evaluate EDP-938 in the Virus Challenge Model
Primary Purpose
RSV Infection
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
EDP-938 Dose 1
EDP-938 Dose 2
Placebo
EDP-938 Dose 3
EDP-938 Dose 4
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for RSV Infection focused on measuring challenge study, RSV, antiviral, RSV-A Memphis 37b
Eligibility Criteria
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
Sites / Locations
- hVIVO Services Limited (hVIVO)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Arm Label
EDP-938 Arm A
EDP-938 Arm B
Placebo Arm C
EDP-938 Arm D
EDP-938 Arm E
Placebo Arm F
Arm Description
Subjects will take EDP-938 Dose 1 oral suspension for 5 days
Subjects will take EDP-938 Dose 2 oral suspension for 5 days
Subjects will take matching placebo oral suspension for 5 days
Subjects will take EDP-938 Dose 3 oral suspension for 5 days
Subjects will take EDP-938 Dose 4 oral suspension for 5 days
Subjects will take matching placebo oral suspension for 5 days
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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
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.
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.
Total Weight of Nasal Mucus Produced
Measured via weighed paper tissues and reported as a mean total across all study days.
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.
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.
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).
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).
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.
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.
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.
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.
Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938
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.
Volume of Distribution at Steady State (Vss/F) of EDP-938
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03691623
First Posted
September 28, 2018
Last Updated
April 6, 2022
Sponsor
Enanta Pharmaceuticals, Inc
Collaborators
hVIVO Services Limited
1. Study Identification
Unique Protocol Identification Number
NCT03691623
Brief Title
A Phase 2a Study to Evaluate EDP-938 in the Virus Challenge Model
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
October 15, 2018 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
October 18, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enanta Pharmaceuticals, Inc
Collaborators
hVIVO Services Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RSV Infection
Keywords
challenge study, RSV, antiviral, RSV-A Memphis 37b
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
179 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EDP-938 Arm A
Arm Type
Experimental
Arm Description
Subjects will take EDP-938 Dose 1 oral suspension for 5 days
Arm Title
EDP-938 Arm B
Arm Type
Experimental
Arm Description
Subjects will take EDP-938 Dose 2 oral suspension for 5 days
Arm Title
Placebo Arm C
Arm Type
Placebo Comparator
Arm Description
Subjects will take matching placebo oral suspension for 5 days
Arm Title
EDP-938 Arm D
Arm Type
Experimental
Arm Description
Subjects will take EDP-938 Dose 3 oral suspension for 5 days
Arm Title
EDP-938 Arm E
Arm Type
Experimental
Arm Description
Subjects will take EDP-938 Dose 4 oral suspension for 5 days
Arm Title
Placebo Arm F
Arm Type
Placebo Comparator
Arm Description
Subjects will take matching placebo oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
EDP-938 Dose 1
Intervention Description
Oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
EDP-938 Dose 2
Intervention Description
Oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
EDP-938 Dose 3
Intervention Description
Oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
EDP-938 Dose 4
Intervention Description
Oral suspension for 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral suspension for 5 days
Primary Outcome Measure Information:
Title
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
Description
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.
Time Frame
Twice daily on Day 2 through Day 11 and once on Day 12
Secondary Outcome Measure Information:
Title
Area Under the Curve (AUC) of Total Symptom Score
Description
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 Frame
Three times daily on Day 0 to Day 11, once on Day 12
Title
Peak Total Symptom Score
Description
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
Time Frame
Day 2 to Day 12
Title
Total Symptom Score
Description
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 Frame
Day 2 to Day 9
Title
Time to Peak Total Symptom Score
Description
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.
Time Frame
Day 2 to Day 12
Title
Time to Resolution From Peak Total Symptom Score
Description
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.
Time Frame
Day 2 to Day 12
Title
Total Weight of Nasal Mucus Produced
Description
Measured via weighed paper tissues and reported as a mean total across all study days.
Time Frame
Day 2 to Day 12
Title
Peak Viral Load
Description
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 Frame
Day 2 to Day 12
Title
Time to Peak Viral Load
Description
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.
Time Frame
Day 2 to Day 12
Title
Time to Resolution From Peak Viral Load
Description
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 Frame
Day 2 to Day 12
Title
Time to Cessation of Virus Detection
Description
Time to cessation of virus detection was measured by nasal wash quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Time Frame
Day 2 to Day 12
Title
Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Day 2 to Day 28
Title
Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938
Time Frame
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
Title
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
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Volume of Distribution at Steady State (Vss/F) of EDP-938
Time Frame
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
Title
Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
Day 2 and Day 7; 12 hours post-dose
Title
Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
Day 2 and Day 7; 24 hours post-dose
Title
Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites
Description
The metabolites of EDP-938 that were assessed were EP-024636, EP-024594 and EP-024595.
Time Frame
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
Title
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC
Description
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.
Time Frame
Day 2 to Day 18
Title
Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC
Description
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.
Time Frame
Day 2 to Day 18
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enanta Pharmaceuticals, Inc
Organizational Affiliation
Enanta Pharmaceuticals, Inc
Official's Role
Study Director
Facility Information:
Facility Name
hVIVO Services Limited (hVIVO)
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
35172056
Citation
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.
Results Reference
derived
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A Phase 2a Study to Evaluate EDP-938 in the Virus Challenge Model
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