Clinical trial NCT03691623: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: RSV Infection
Keywords: challenge study
RSV
antiviral
RSV-A Memphis 37b
Lead sponsor: Enanta Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: hVIVO Services Limited
First posted: 2018-10-02
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
timeFrame: Twice daily on Day 2 through Day 11 and once on Day 12
Secondary outcomes:
measure: Area Under the Curve (AUC) of Total Symptom Score
timeFrame: Three times daily on Day 0 to Day 11, once on Day 12
measure: Peak Total Symptom Score
timeFrame: Day 2 to Day 12
measure: Total Symptom Score
timeFrame: Day 2 to Day 9
measure: Time to Peak Total Symptom Score
timeFrame: Day 2 to Day 12
measure: Time to Resolution From Peak Total Symptom Score
timeFrame: Day 2 to Day 12
measure: Total Weight of Nasal Mucus Produced
timeFrame: Day 2 to Day 12
measure: Peak Viral Load
timeFrame: Day 2 to Day 12
measure: Time to Peak Viral Load
timeFrame: Day 2 to Day 12
measure: Time to Resolution From Peak Viral Load
timeFrame: Day 2 to Day 12
measure: Time to Cessation of Virus Detection
timeFrame: Day 2 to Day 12
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 2 to Day 28
measure: Maximum Plasma Concentration (Cmax) of EDP-938 and Its Metabolites
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of EDP-938 and Its Metabolites
timeFrame: 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
measure: Terminal Phase Half-Life (t1/2) of EDP-938 and Its Metabolites
timeFrame: 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
measure: Apparent Systemic Clearance at Steady State (CLss/F) of EDP-938
timeFrame: 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
measure: 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
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss/F) of EDP-938
timeFrame: 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
measure: Plasma Concentration at 12 Hours (C12) of EDP-938 and Its Metabolites
timeFrame: Day 2 and Day 7; 12 hours post-dose
measure: Plasma Concentration at 24 Hours (C24) of EDP-938 and Its Metabolites
timeFrame: Day 2 and Day 7; 24 hours post-dose
measure: Area Under the Concentration Time Curve Time 0 to Time of Last Quantifiable Concentration (AUC0-last) of EDP-938 and Its Metabolites
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of EDP-938 and Its Metabolites
timeFrame: 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
measure: Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Viral Load AUC
timeFrame: Day 2 to Day 18
measure: Number of Participants With Correlation of Plasma Pharmacokinetic (PK) Area Under the Curve (AUC) and Total Symptom Score (TSS) AUC
timeFrame: Day 2 to Day 18
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: hVIVO Services Limited (hVIVO)
Study officials:
affiliation: Enanta Pharmaceuticals, Inc
name: Enanta Pharmaceuticals, Inc
role: STUDY_DIRECTOR
References:
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.