A Study to Evaluate EDP 938 Regimens in Children With RSV

Enanta Pharmaceuticals, Inc99 enrolled

Overview

A 2-part study to evaluate the safety, pharmacokinetics and efficacy of EDP-938 in children with RSV infection.

This is a randomized, double-blind, dose ranging, placebo-controlled study in respiratory syncytial virus (RSV) among hospitalized and non-hospitalized children aged from 28 days to 36 months, assessing the safety, tolerability, pharmacokinetics, clinical outcome and antiviral activity of a 5 day treatment with EDP-938.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Respiratory Syncytial Virus (RSV)

Interventions

EDP-938DRUG

Oral suspension

PlaceboDRUG

Placebo oral suspension to match EDP-938

Eligibility

Sex: ALLMin age: 28 DaysMax age: 36 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female who is either ≥6 months to ≤36 months (for Age Group 1) or ≥28 days to \<6 months (for Age Group 2), defined at the time of randomization. Subjects in Age Group 2 must have been born ≥29 weeks of gestation to be eligible. * Subjects diagnosed with RSV infection * Subjects with signs of an acute respiratory illness with onset ≤7 days for Part 1 and ≤5 days for Part 2 before the time of signing the ICF * In the Investigator's opinion, the subject's caregiver understands and is able to comply with protocol requirements, instructions, and protocol-stated restrictions, and the subject is likely to complete the study as planned Exclusion Criteria: * Use of or anticipated need for invasive mechanical ventilation, cardiopulmonary bypass, hemodialysis, or extracorporeal membrane oxygenation; or subjects who are not expected to survive the current illness * Underlying immune deficiency, (e.g., from confirmed human immunodeficiency virus infection or use of an immunosuppressive medication except immunoglobulin A deficiency) * Receipt of (within 12 months before Screening) or on a waiting list for a bone marrow, stem cell, or solid organ transplant, or who received radiation or chemotherapy (within 12 months before screening) * Receiving chronic oxygen therapy at home before admission * Subjects whose mother received an investigational RSV vaccination while pregnant with the subject if they were born at term (≥37 weeks of gestation) and are less than 12 months of age * In Part 2, subjects dosed with an investigational or approved medication that is intended to prevent or treat RSV infection within the following times before the first dose of study drug: ribavirin 35 days; palivizumab 100 days; nirsevimab 350 days; other RSV-specific monoclonal antibody 5 half-lives of the specific antibody; RSV vaccines 12 months.

Locations (78)

Outcomes

Primary Outcomes

Part 1: Concentrations of EDP-938 in Plasma

Plasma concentrations of EDP-938 were assessed at the designated time points.

Time frame: 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5

Part 1: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

TEAEs were defined as any event, side effect, or untoward medical occurrence in a participant enrolled in a clinical study whether or not it was considered to have a causal relationship to the study drug and first occurred or worsened during the post-baseline phase compared to baseline. Clinically significant changes from baseline in vital signs and clinical laboratory results were reported as TEAEs.

Time frame: Day 1 to Day 28

Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples

Daily change from baseline in RSV shedding was defined as the daily change from baseline in RSV ribonucleic acid (RNA) viral load and was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) from nasal swabs. The model included treatment group (EDP-938, placebo) and Day (3, 5, 9, and 14) as fixed effect, associated baseline, and treatment group by Day interaction term as factors. An unstructured covariance matrix was imposed. The Satterthwaite approximation is used to estimate the denominator degrees of freedom.

Time frame: Baseline and pre-dose on Days 3, 5, 9, and 14

Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples

Daily change from baseline in RSV shedding was defined as the daily change from baseline in RSV RNA viral load and was measured using RT-qPCR from nasal swabs. The model included treatment group (EDP-938, placebo) and Day (3, 5, 9, and 14) as fixed effect, associated baseline, and treatment group by Day interaction term as factors. An unstructured covariance matrix was imposed.The Satterthwaite approximation is used to estimate the denominator degrees of freedom.

Time frame: Baseline and pre-dose on Days 3, 5, 9, and 14

Data from ClinicalTrials.gov

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Secondary Outcomes

Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load

Time frame: Pre-dose on Day 1 through pre-dose on Days 3, 5, 9 and 14

Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load

The RSV RNA viral load was measured using RT-qPCR from nasal swabs. The AUC was calculated using the trapezoid rule. The AUC was calculated based on all available assessments collected on Days 1, 3, 5, 9 and 14 and the actual date/time of each assessment was used for the calculation. The model included treatment group (EDP-938, placebo) and Day (3, 5, 9, and 14) as fixed effect, associated baseline, and treatment group by day interaction term as factors. An unstructured covariance matrix was imposed. The Satterthwaite approximation was used to estimate the denominator degrees of freedom.

Time frame: Baseline (Pre-dose on Day 1) through pre-dose on Days 3, 5, 9 and 14

Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples

Daily change from baseline in RSV shedding in nasal swab samples was defined as the absolute daily change from baseline in RSV RNA viral load and measured using RT-qPCR from nasal swabs.

Time frame: Baseline to pre-dose on Days 3, 5, 9, and Day 14

Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD)

The RSV RNA viral load was measured using RT-qPCR from nasal swabs.

Time frame: Pre-dose on Days 3, 5, 9 and 14

Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD

The RSV RNA viral load was measured using RT-qPCR from nasal swabs.

Time frame: Pre-dose on Days 3, 5, 9 and 14

Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable

Time to RSV RNA viral load being undetectable was calculated as: first date of RSV RNA viral load target not detected (TND) after which no further samples had detectable RSV RNA viral load - date of first dose.

Time frame: Day 1 to Day 28

Pooled Population: Time to RSV RNA Viral Load Being Undetectable

Time to RSV RNA viral load being undetectable was calculated as: first date of RSV RNA viral load TND after which no further samples had detectable RSV RNA viral load - date of first dose.

Time frame: Day 1 to Day 28

Part 2: Number of Participants Who Experienced a TEAE

Time frame: Day 1 to Day 28

Pooled Population: Number of Participants Who Experienced a TEAE

Time frame: Day 1 to Day 28

Part 2: Concentrations of EDP-938 in Plasma

Plasma concentrations of EDP-938 were assessed at the designated time points.

Time frame: 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5

Pooled Population: Concentrations of EDP-938 in Plasma

Plasma concentrations of EDP-938 were assessed at the designated time points.

Time frame: 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5

Part 2: Time to First Hospital Discharge for Hospitalized Participants

Time to first discharge for participants who were hospitalized at randomization was calculated as: date/time of first discharge - date/time of first dose with conversion to days. For participants with continuous hospitalization, the last date of discharge from the continuous hospitalization was used.

Time frame: Day 1 to Day 28

Pooled Population: Time to First Hospital Discharge for Hospitalized Participants

Time frame: Day 1 to Day 28

Part 2: Time to Use of Oxygen for Hospitalized Participants Who Were Not Receiving Oxygen at the Time They Received the First Dose of Study Drug

For participants were were hospitalized at randomization, time to use of oxygen for hospitalization participants who were not receiving oxygen at the time they received the first dose of study drug was calculated as: first date/time of receiving oxygen - date/time of first dose of study drug with conversion to days.

Time frame: Day 1 to Day 28

Pooled Population: Time to Use of Oxygen for Hospitalized Participants Who Were Not Receiving Oxygen at the Time They Received the First Dose of Study Drug

Time frame: Day 1 to Day 28

Part 2: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug

The numerator in the percentage calculation was defined by the number of participants who developed a new requirement for oxygen supplementation or new increase in oxygen requirements after the first dose of study drug, based on the response of "yes" to the "Is this an increase of oxygen supplementation compared to previous use?" question on the Oxygen Supplementation case report form (CRF). The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Pooled Population: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug

The numerator in the percentage calculation was defined by the number of participants who developed a new requirement for oxygen supplementation or new increase in oxygen requirements after the first dose of study drug, based on the response of "yes" to the "Is this an increase of oxygen supplementation compared to previous use?" question on the Oxygen Supplementation CRF. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Part 2: Time to Mechanical Ventilation for Hospitalized Participants

Time to mechanical ventilation for participants who were hospitalized at randomization was calculated as: first date/time of mechanical ventilation - date/time of first dose of study drug with conversion to days. Participants who were on mechanical ventilation before their first dose of study drug were excluded from the analysis.

Time frame: Day 1 to Day 28

Pooled Population: Time to Mechanical Ventilation for Hospitalized Participants

Time frame: Day 1 to Day 28

Part 2: Percentage of Hospitalized Participants Who Required Mechanical Ventilation

The numerator in the percentage calculation was defined by the number of participants who developed a new requirement for mechanical ventilation after the first dose of study drug. Participants on mechanical ventilation prior to the first dose of study drug were excluded from analysis. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Pooled Population: Percentage of Hospitalized Participants Who Required Mechanical Ventilation

Time frame: Day 1 to Day 28

Part 2: Percentage of Hospitalized Participants Who Died During the Study

The percentage of hospitalized participants who died during the study included deaths from any cause. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Pooled Population: Percentage of Hospitalized Participants Who Died During the Study

The percentage of hospitalized participants who died during the study included deaths from any cause. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Part 2: Time to Hospitalization for Initial Outpatients Who Were Subsequently Hospitalized

Time to hospitalization for initial outpatients who are not hospitalized at randomization but subsequently hospitalized was calculated as: first date/time of hospitalization - date/time of first dose with conversion to days.

Time frame: Day 1 to Day 28

Pooled Population: Time to Hospitalization for Initial Outpatients Who Were Subsequently Hospitalized

Time frame: Day 1 to Day 28

Part 2: Percentage of Outpatients Who Were Subsequently Hospitalized or Died

Participants who were hospitalized at randomization were excluded from the analysis. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Pooled Population: Percentage of Outpatients Who Were Subsequently Hospitalized or Died

Participants who were hospitalized at randomization were excluded from the analysis. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods.

Time frame: Day 1 to Day 28

Part 2: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized

Resolution of symptoms was defined as the first of 2 consecutive timepoints where each of the seven symptoms assessed by the Parent/Caregiver Respiratory Syncytial Virus (RSV) Foundation (ReSVinet) score was 0 (not present) or 1 (mild). Time to resolution of symptoms for outpatients who were not hospitalized was calculated as: first date/time of resolution of symptoms - date/time of first dose with conversion to days. Participants who did not achieve resolution and had not been followed through the Day 14 visit or completed the Day 14 questionnaire were censored at Day 14. During the study, the parent(s)/caregiver(s) assessed the severity of RSV-related signs and symptoms. The ReSVinet assessed 7 symptoms, with each symptom being rated from 0 (not present) to 3 (severe), apart from fever which was scored from 0-2. The full range was 0 to 20 with higher scores representing more severe disease.

Time frame: Day 1 to Day 14

Pooled Population: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized

Resolution of symptoms was defined as the first of 2 consecutive timepoints where each of the seven symptoms assessed by the Parent/Caregiver ReSVinet score was 0 (not present) or 1 (mild). Time to resolution of symptoms for outpatients who were not hospitalized was calculated as: first date/time of resolution of symptoms - date/time of first dose with conversion to days. Participants who did not achieve resolution and had not been followed through the Day 14 visit or completed the Day 14 questionnaire were censored at Day 14. During the study, the parent(s)/caregiver(s) assessed the severity of RSV-related signs and symptoms. The ReSVinet assessed 7 symptoms, with each symptom being rated from 0 (not present) to 3 (severe), apart from fever which was scored from 0-2. The full range was 0 to 20 with higher scores representing more severe disease.

Time frame: Day 1 to Day 14