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

RSV Infection Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03691623
• Other study ID #: EDP 938-101
• Status: Completed
• Phase: Phase 2
• Start date: October 15, 2018
• Est. completion date: October 18, 2019

Study information

• Verified date: August 2019
• Source: Enanta Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: October 18, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Infections
• Respiratory Syncytial Virus Infections
• RSV Infection

Intervention

Drug:
• EDP-938 Dose 1
Oral suspension for 5 days
• EDP-938 Dose 2
Oral suspension for 5 days
• Placebo
Oral suspension for 5 days
• EDP-938 Dose 3
Oral suspension for 5 days
• EDP-938 Dose 4
Oral suspension for 5 days
• Placebo
Oral suspension for 5 days

Locations

Country	Name	City	State
United Kingdom	hVIVO Services Limited (hVIVO)	London

Sponsors (2)

Lead Sponsor	Collaborator
Enanta Pharmaceuticals	hVIVO Services Limited

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Terminal Phase Rate Constant Calculated by Linear Regression of the Terminal Loglinear Portion of the Concentration vs. Time Curve (?z) 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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