Respiratory Syncytial Virus (RSV)
Conditions
Keywords
Respiratory Syncytial Virus, RSV, Pediatric study
Brief summary
A 2-part study to evaluate the safety, pharmacokinetics and efficacy of EDP-938 in children with RSV infection.
Detailed description
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.
Interventions
DRUGEDP-938
Oral suspension
DRUGPlacebo
Placebo oral suspension to match EDP-938
Sponsors
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
28 Days to 36 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Concentrations of EDP-938 in Plasma | 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5 | Plasma concentrations of EDP-938 were assessed at the designated time points. |
| Part 1: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 28 | 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. |
| Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Baseline and pre-dose on Days 3, 5, 9, and 14 | 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. |
| Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Baseline and pre-dose on Days 3, 5, 9, and 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Pre-dose on Days 3, 5, 9 and 14 | The RSV RNA viral load was measured using RT-qPCR from nasal swabs. |
| Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable | Day 1 to Day 28 | 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. |
| Pooled Population: Time to RSV RNA Viral Load Being Undetectable | Day 1 to Day 28 | 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. |
| Part 2: Number of Participants Who Experienced a TEAE | Day 1 to Day 28 | 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. |
| Pooled Population: Number of Participants Who Experienced a TEAE | Day 1 to Day 28 | 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. |
| Part 2: Concentrations of EDP-938 in Plasma | 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5 | Plasma concentrations of EDP-938 were assessed at the designated time points. |
| Pooled Population: Concentrations of EDP-938 in Plasma | 3 hours post-dose on Day 1 and pre-dose on Day 2 (hospitalized participants only), Day 3, and Day 5 | Plasma concentrations of EDP-938 were assessed at the designated time points. |
| Part 2: Time to First Hospital Discharge for Hospitalized Participants | Day 1 to Day 28 | 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. |
| Pooled Population: Time to First Hospital Discharge for Hospitalized Participants | Day 1 to Day 28 | 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. |
| 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 | Day 1 to Day 28 | 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. |
| 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 | Day 1 to Day 28 | 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. |
| Part 2: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | Day 1 to Day 28 | 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. |
| Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Pre-dose on Day 1 through pre-dose on Days 3, 5, 9 and 14 | 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. |
| Part 2: Time to Mechanical Ventilation for Hospitalized Participants | Day 1 to Day 28 | 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. |
| Pooled Population: Time to Mechanical Ventilation for Hospitalized Participants | Day 1 to Day 28 | 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. |
| Part 2: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | Day 1 to Day 28 | 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. |
| Pooled Population: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | Day 1 to Day 28 | 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. |
| Part 2: Percentage of Hospitalized Participants Who Died During the Study | Day 1 to Day 28 | 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. |
| Pooled Population: Percentage of Hospitalized Participants Who Died During the Study | Day 1 to Day 28 | 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. |
| Part 2: Time to Hospitalization for Initial Outpatients Who Were Subsequently Hospitalized | Day 1 to Day 28 | 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. |
| Pooled Population: Time to Hospitalization for Initial Outpatients Who Were Subsequently Hospitalized | Day 1 to Day 28 | 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. |
| Part 2: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | Day 1 to Day 28 | Participants who were hospitalized at randomization were excluded from the analysis. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods. |
| Pooled Population: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | Day 1 to Day 28 | Participants who were hospitalized at randomization were excluded from the analysis. The 95% confidence interval was reported using the Clopper Pearson confidence interval methods. |
| Part 2: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | Day 1 to Day 14 | 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. |
| Pooled Population: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | Day 1 to Day 14 | 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. |
| Pooled Population: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | Day 1 to Day 28 | 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. |
| Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Baseline (Pre-dose on Day 1) through pre-dose on Days 3, 5, 9 and 14 | 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. |
| Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Baseline to pre-dose on Days 3, 5, 9, and Day 14 | 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. |
| Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Pre-dose on Days 3, 5, 9 and 14 | The RSV RNA viral load was measured using RT-qPCR from nasal swabs. |
Countries
Argentina, Australia, Brazil, Germany, Israel, Mexico, New Zealand, Poland, Romania, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 99 participants were enrolled at 78 sites across 15 countries between April 2022 and August 2024.
Pre-assignment details
Participants were randomized 2:1 (Part 1) or 4:1 (Part 2) to EDP-938:placebo.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Group 1: EDP-938 Participants aged ≥ 6 months to \< 12 months received oral 5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. Participants aged ≥ 12 months to ≤ 36 months received oral 5 mg/kg or 7.5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. | 23 |
| Part 1, Group 2: EDP-938 Participants aged ≥ 28 days to \< 6 months received oral 5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. | 13 |
| Part 1, Group 1: Placebo Participants aged between ≥ 6 months and ≤ 36 months received oral doses of placebo matching EDP-938 QD from Day 1 to Day 5 of the study. | 10 |
| Part 1, Group 2: Placebo Participants aged between ≥ 28 days and \< 6 months received oral doses of placebo matching EDP-938 QD from Day 1 to Day 5 of the study. | 6 |
| Part 2, Group 1: EDP-938 Participants aged ≥ 6 months to \< 12 months received oral 5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. Participants aged ≥ 12 months to ≤ 36 months received oral 7.5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. | 19 |
| Part 2, Group 2: EDP-938 Participants aged ≥ 28 days to \< 6 months received oral 5 mg/kg doses of EDP-938 QD from Day 1 to Day 5 of the study. | 15 |
| Part 2, Group 1: Placebo Participants aged between ≥ 6 months and ≤ 36 months received oral doses of placebo matching EDP-938 QD from Day 1 to Day 5 of the study. | 6 |
| Part 2, Group 2: Placebo Participants aged between ≥ 28 days and \< 6 months received oral doses of placebo matching EDP-938 QD from Day 1 to Day 5 of the study. | 4 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Miscellaneous | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part 2, Group 2: Placebo | Part 1, Group 2: Placebo | Part 1, Group 1: Placebo | Part 1, Group 2: EDP-938 | Part 1, Group 1: EDP-938 | Part 2, Group 1: Placebo | Part 2, Group 2: EDP-938 | Part 2, Group 1: EDP-938 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized ≥ 12 months to ≤ 36 months | 36 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 16 Participants | 3 Participants | 0 Participants | 11 Participants |
| Age, Customized ≥ 28 days to < 3 months | 22 Participants | 2 Participants | 4 Participants | 0 Participants | 9 Participants | 0 Participants | 0 Participants | 7 Participants | 0 Participants |
| Age, Customized ≥ 3 months to < 6 months | 16 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 8 Participants | 0 Participants |
| Age, Customized ≥ 6 months to < 12 months | 22 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 7 Participants | 3 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 12 Participants | 3 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 1 Participants | 4 Participants | 7 Participants | 10 Participants | 11 Participants | 3 Participants | 9 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Hospitalization Status on Day 1 No | 19 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 7 Participants | 2 Participants | 3 Participants | 2 Participants |
| Hospitalization Status on Day 1 Yes | 77 Participants | 3 Participants | 5 Participants | 8 Participants | 12 Participants | 16 Participants | 4 Participants | 12 Participants | 17 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 0 Participants | 2 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Reported | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 62 Participants | 2 Participants | 2 Participants | 3 Participants | 11 Participants | 18 Participants | 4 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Female | 49 Participants | 1 Participants | 5 Participants | 3 Participants | 5 Participants | 12 Participants | 5 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 47 Participants | 3 Participants | 1 Participants | 7 Participants | 8 Participants | 11 Participants | 1 Participants | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 16 | 0 / 34 | 0 / 10 |
| other Total, other adverse events | 7 / 36 | 7 / 16 | 9 / 34 | 4 / 10 |
| serious Total, serious adverse events | 0 / 36 | 2 / 16 | 1 / 34 | 0 / 10 |
Outcome results
Primary
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
Population: Pharmacokinetic (PK) Population: Included all participants in Part 1 who received one full dose of study drug and had samples with quantifiable plasma levels to allow for estimation of PK parameters. Per protocol, data were analyzed per age group and dose received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 5 | 528.563 ng/mL | Standard Deviation 284.601 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 2 | 368.400 ng/mL | Standard Deviation 149.8741 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 3 | 448.000 ng/mL | Standard Deviation 229.1026 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 1 | 1132.222 ng/mL | Standard Deviation 397.4289 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 5 | 201.750 ng/mL | Standard Deviation 98.6623 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 1 | 1989.500 ng/mL | Standard Deviation 1331.5646 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 2 | 399.250 ng/mL | Standard Deviation 423.9515 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 5 | 431.429 ng/mL | Standard Deviation 637.5664 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 1 | 1819.286 ng/mL | Standard Deviation 809.9508 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 3 | 346.000 ng/mL | Standard Deviation 54.7449 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 2 | 502.350 ng/mL | Standard Deviation 379.6487 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 1 | 1420.000 ng/mL | Standard Deviation 604.814 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 2 | 249.675 ng/mL | Standard Deviation 294.5416 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 3 | 97.533 ng/mL | Standard Deviation 64.9043 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 5 | 252.043 ng/mL | Standard Deviation 329.2155 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 5 | 180.622 ng/mL | Standard Deviation 158.3268 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 1 | 1428.250 ng/mL | Standard Deviation 817.4801 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 2 | 238.900 ng/mL | Standard Deviation 239.0287 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1: Concentrations of EDP-938 in Plasma | Day 3 | 116.250 ng/mL | Standard Deviation 43.4871 |
Primary
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
Population: Safety Population: Included all participants in Part 1 who received any dose (including partial doses) of any study drug. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 14 Participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 9 Participants |
Primary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 3 | -1.33 log10 copies/mL | Standard Error 0.297 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 5 | -3.04 log10 copies/mL | Standard Error 0.354 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 9 | -3.65 log10 copies/mL | Standard Error 0.381 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 14 | -4.87 log10 copies/mL | Standard Error 0.388 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 14 | -5.71 log10 copies/mL | Standard Error 0.677 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 3 | -0.37 log10 copies/mL | Standard Error 0.533 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 9 | -3.22 log10 copies/mL | Standard Error 0.68 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Model-Adjusted Daily Change From Baseline in Respiratory Syncytial Virus (RSV) Shedding in Nasal Swab Samples | Day 5 | -1.62 log10 copies/mL | Standard Error 0.627 |
Comparison: Day 3: EDP-938 Versus Placebop-value: 0.124995% CI: [-2.21, 0.28]Mixed-effect Model of Repeated Measures
Comparison: Day 5: EDP-938 Versus Placebop-value: 0.05895% CI: [-2.88, 0.05]Mixed-effect Model of Repeated Measures
Comparison: Day 9: EDP-938 Versus Placebop-value: 0.587795% CI: [-2.02, 1.16]Mixed-effect Model of Repeated Measures
Comparison: Day 14: EDP-938 Versus Placebop-value: 0.293295% CI: [-0.76, 2.43]Mixed-effect Model of Repeated Measures
Primary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 3 | -1.53 log10 copies/mL | Standard Error 0.192 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 5 | -2.95 log10 copies/mL | Standard Error 0.23 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 9 | -4.57 log10 copies/mL | Standard Error 0.275 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 14 | -5.01 log10 copies/mL | Standard Error 0.278 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 14 | -5.35 log10 copies/mL | Standard Error 0.462 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 3 | -1.36 log10 copies/mL | Standard Error 0.331 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 9 | -3.87 log10 copies/mL | Standard Error 0.475 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Model-Adjusted Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 5 | -2.62 log10 copies/mL | Standard Error 0.392 |
Comparison: Day 3: EDP-938 Versus Placebop-value: 0.657495% CI: [-0.93, 0.59]Mixed-effect Model of Repeated Measures
Comparison: Day 5: EDP-938 Versus Placebop-value: 0.472895% CI: [-1.23, 0.58]Mixed-effect Model of Repeated Measures
Comparison: Day 9: EDP-938 Versus Placebop-value: 0.205895% CI: [-1.79, 0.39]Mixed-effect Model of Repeated Measures
Comparison: Day 14: EDP-938 Versus Placebop-value: 0.539195% CI: [-0.74, 1.41]Mixed-effect Model of Repeated Measures
Secondary
Part 1 and Part 2: Area Under the Curve (AUC) for 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.
Time frame: Pre-dose on Day 1 through pre-dose on Days 3, 5, 9 and 14
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 3 | 17.80 log10 copies/mL*Days | Standard Deviation 4.522 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 5 | 25.54 log10 copies/mL*Days | Standard Deviation 8.301 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 9 | 36.03 log10 copies/mL*Days | Standard Deviation 16.229 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 14 | 42.85 log10 copies/mL*Days | Standard Deviation 24.99 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 5 | 24.55 log10 copies/mL*Days | Standard Deviation 8.457 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 9 | 35.20 log10 copies/mL*Days | Standard Deviation 17.156 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 14 | 44.16 log10 copies/mL*Days | Standard Deviation 25.056 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 3 | 17.26 log10 copies/mL*Days | Standard Deviation 4.691 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 9 | 37.00 log10 copies/mL*Days | Standard Deviation 13.652 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 5 | 24.76 log10 copies/mL*Days | Standard Deviation 7.914 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 14 | 45.49 log10 copies/mL*Days | Standard Deviation 21.109 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 3 | 17.15 log10 copies/mL*Days | Standard Deviation 4.663 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 14 | 42.17 log10 copies/mL*Days | Standard Deviation 19.864 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 5 | 26.22 log10 copies/mL*Days | Standard Deviation 7.069 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 3 | 16.91 log10 copies/mL*Days | Standard Deviation 3.266 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Area Under the Curve (AUC) for RSV RNA Viral Load | Day 1 through Day 9 | 40.39 log10 copies/mL*Days | Standard Deviation 13.371 |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Included only participants with detectable viral load at baseline and non-missing viral load assessment at the respective visit and was used as a denominator in the percentage population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 3 | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 5 | 12.1 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 9 | 62.5 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 14 | 61.3 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 5 | 16.7 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 9 | 36.4 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 14 | 58.3 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 3 | 8.3 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 9 | 28.0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 5 | 22.2 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 14 | 63.0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 3 | 3.6 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 14 | 88.9 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 5 | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 3 | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Percentage of Participants With RSV RNA Viral Load Below the Limit of Detection (LOD) | Day 9 | 25.0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable | 10.59 days | Standard Deviation 3.661 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable | 12.33 days | Standard Deviation 3.018 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable | 12.46 days | Standard Deviation 3.235 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 1 and Part 2: Time to RSV RNA Viral Load Being Undetectable | 12.19 days | Standard Deviation 3.04 |
Secondary
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
Population: Efficacy Population: Included all participants in Part 1 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 3 | -1.68 log10 copies/mL | Standard Deviation 1.239 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 5 | -2.91 log10 copies/mL | Standard Deviation 1.634 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 9 | -5.34 log10 copies/mL | Standard Deviation 2.338 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 14 | -5.11 log10 copies/mL | Standard Deviation 2.378 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 14 | -5.15 log10 copies/mL | Standard Deviation 2.118 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 3 | -2.17 log10 copies/mL | Standard Deviation 1.948 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 9 | -4.41 log10 copies/mL | Standard Deviation 1.897 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 1: Daily Change From Baseline in RSV Shedding in Nasal Swab Samples | Day 5 | -3.44 log10 copies/mL | Standard Deviation 1.585 |
Secondary
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
Population: PK Population: Included all participants in Part 2 who received one full dose of study drug and had samples with quantifiable plasma levels to allow for estimation of PK parameters. Per protocol, data were analyzed per age group and dose received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 1 | 1116.286 ng/mL | Standard Deviation 217.9983 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 2 | 585.400 ng/mL | Standard Deviation 119.6089 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 3 | 194.000 ng/mL | — |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 5 | 516.333 ng/mL | Standard Deviation 247.6697 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 2 | 273.500 ng/mL | Standard Deviation 150.4616 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 3 | 926.000 ng/mL | Standard Deviation 57.9828 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 5 | 519.714 ng/mL | Standard Deviation 436.813 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 1 | 1169.903 ng/mL | Standard Deviation 802.0744 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 3 | 112.000 ng/mL | — |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 2 | 140.783 ng/mL | Standard Deviation 73.3099 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 5 | 69.110 ng/mL | Standard Deviation 40.4604 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 1 | 1551.429 ng/mL | Standard Deviation 363.8419 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 5 | 153.450 ng/mL | Standard Deviation 102.4372 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 2 | 200.700 ng/mL | Standard Deviation 134.3896 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 1 | 1368.111 ng/mL | Standard Deviation 469.7815 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Part 2: Concentrations of EDP-938 in Plasma | Day 3 | 115.967 ng/mL | Standard Deviation 84.9347 |
Secondary
Part 2: Number of Participants Who Experienced a 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
Population: Safety Population: Included all participants in Part 2 who received any dose (including partial doses) of any study drug. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Number of Participants Who Experienced a TEAE | 14 Participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Number of Participants Who Experienced a TEAE | 4 Participants |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were hospitalized at randomization and/or during the study were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Percentage of Hospitalized Participants Who Died During the Study | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Percentage of Hospitalized Participants Who Died During the Study | 0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only hospitalized participants who were not on mechanical ventilation prior to the first dose of study drug were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | 0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were hospitalized at randomization and/or during the study were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | 24.1 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | 28.6 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were not hospitalized at randomization were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | 0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Only participants who were hospitalized at randomization were included. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Time to First Hospital Discharge for Hospitalized Participants | 3.93 days | Standard Deviation 1.87 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Time to First Hospital Discharge for Hospitalized Participants | 4.00 days | Standard Deviation 3.367 |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. As only participants who were not hospitalized at randomization but subsequently hospitalized were included, no data were collected for this outcome measure.
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. As only participants who were hospitalized at baseline and experienced mechanical ventilation were included, no data were collected for this outcome measure.
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were not hospitalized were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Part 2: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | 2.60 days | Standard Deviation 1.686 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Part 2: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | 1.49 days | Standard Deviation 0.702 |
Secondary
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
Population: Efficacy Population: Included all participants in Part 2 who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. As there were no participants in Part 2 in both arms who were hospitalized at randomization who were not receiving oxygen at the time they received the first dose of study drug, no data were collected for this outcome measure.
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 9 | -21.04 log10 copies/mL*Days | Standard Error 1.319 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 3 | -1.53 log10 copies/mL*Days | Standard Error 0.192 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 14 | -45.00 log10 copies/mL*Days | Standard Error 2.105 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 5 | -6.00 log10 copies/mL*Days | Standard Error 0.54 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 14 | -41.36 log10 copies/mL*Days | Standard Error 3.619 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 9 | -18.32 log10 copies/mL*Days | Standard Error 2.272 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 5 | -5.33 log10 copies/mL*Days | Standard Error 0.93 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: AUC of Change From Baseline in RSV RNA Viral Load | Day 1 through Day 3 | -1.36 log10 copies/mL*Days | Standard Error 0.331 |
Comparison: Day 1 through Day 3: EDP-938 Versus Placebop-value: 0.657495% CI: [-0.93, 0.59]Mixed-effect Model of Repeated Measures
Comparison: Day 1 through Day 5: EDP-938 Versus Placebop-value: 0.535995% CI: [-2.81, 1.47]Mixed-effect Model of Repeated Measures
Comparison: Day 1 through Day 9: EDP-938 Versus Placebop-value: 0.302995% CI: [-7.95, 2.5]Mixed-effect Model of Repeated Measures
Comparison: Day 1 through Day 14: EDP-938 Versus Placebop-value: 0.387195% CI: [-11.98, 4.69]Mixed-effect Model of Repeated Measures
Secondary
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
Population: PK Population: Included all participants who received one full dose of study drug and had samples with quantifiable plasma levels to allow for estimation of PK parameters. Per protocol, data were analyzed per age group and dose received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 2 | 458.817 ng/mL | Standard Deviation 173.0322 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 5 | 522.918 ng/mL | Standard Deviation 257.0945 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 3 | 363.333 ng/mL | Standard Deviation 218.5162 |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 1 | 1125.250 ng/mL | Standard Deviation 321.4278 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 5 | 404.091 ng/mL | Standard Deviation 378.3365 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 2 | 323.800 ng/mL | Standard Deviation 276.9576 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 3 | 926.000 ng/mL | Standard Deviation 57.9828 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 1 | 1443.102 ng/mL | Standard Deviation 1027.5197 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 2 | 285.410 ng/mL | Standard Deviation 293.0727 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 1 | 1685.357 ng/mL | Standard Deviation 619.0267 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 5 | 250.269 ng/mL | Standard Deviation 472.9799 |
| Part 1: EDP-938 5mg/kg (≥ 6 Months to < 12 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 3 | 287.500 ng/mL | Standard Deviation 125.2478 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 2 | 249.675 ng/mL | Standard Deviation 294.5416 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 1 | 1420.000 ng/mL | Standard Deviation 604.814 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 5 | 252.043 ng/mL | Standard Deviation 329.2155 |
| Part 1: EDP-938 5mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 3 | 97.533 ng/mL | Standard Deviation 64.9043 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 5 | 167.835 ng/mL | Standard Deviation 131.6054 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 2 | 221.269 ng/mL | Standard Deviation 191.0117 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 3 | 116.080 ng/mL | Standard Deviation 63.873 |
| Part 1: EDP-938 7.5 mg/kg (≥ 12 Months to ≤ 36 Months) | Pooled Population: Concentrations of EDP-938 in Plasma | Day 1 | 1396.412 ng/mL | Standard Deviation 635.3537 |
Secondary
Pooled Population: Number of Participants Who Experienced a 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
Population: Safety Population: Included all participants who received any dose (including partial doses) of any study drug. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Number of Participants Who Experienced a TEAE | 28 Participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Number of Participants Who Experienced a TEAE | 13 Participants |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were hospitalized at randomization and/or during the study were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Hospitalized Participants Who Died During the Study | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Hospitalized Participants Who Died During the Study | 0 percentage of participants |
Secondary
Pooled Population: 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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only hospitalized participants who were not on mechanical ventilation prior to the first dose of study drug were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Hospitalized Participants Who Required Mechanical Ventilation | 0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were hospitalized at randomization and/or during the study were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | 25.0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Hospitalized Participants Who Required Oxygen Supplementation or Had an Increased Oxygen Requirement After the First Dose of Study Drug | 19.0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were not hospitalized at randomization were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | 0 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Outpatients Who Were Subsequently Hospitalized or Died | 0 percentage of participants |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Included only participants with detectable viral load at baseline and non-missing viral load assessment at the respective visit and was used as a denominator in the percentage population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 3 | 1.6 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 5 | 16.7 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 9 | 47.4 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 14 | 62.1 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 14 | 71.4 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 3 | 4.8 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 9 | 31.6 percentage of participants |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Percentage of Participants With RSV RNA Viral Load Below the LOD | Day 5 | 9.5 percentage of participants |
Secondary
Pooled Population: 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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Only participants who were hospitalized at randomization were included. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Time to First Hospital Discharge for Hospitalized Participants | 3.71 days | Standard Deviation 2.006 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Time to First Hospital Discharge for Hospitalized Participants | 3.57 days | Standard Deviation 2.959 |
Secondary
Pooled Population: 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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. As only participants who were not hospitalized at randomization but subsequently hospitalized were included, no data were collected for this outcome measure.
Secondary
Pooled Population: 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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. As only participants who were hospitalized at baseline and experienced mechanical ventilation after their first dose of study drug were included, no data were collected for this outcome measure.
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only participants who were not hospitalized were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | 2.42 days | Standard Deviation 1.163 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Time to Resolution of Symptoms for Outpatients Who Were Not Hospitalized | 4.20 days | Standard Deviation 5.552 |
Secondary
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
Population: Efficacy Population: Included all participants who received one full dose of study drug and had at least one evaluable measurement while on treatment. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | Pooled Population: Time to RSV RNA Viral Load Being Undetectable | 11.45 days | Standard Deviation 3.57 |
| Part 1: EDP-938 5mg/kg (≥ 3 Months to < 6 Months) | Pooled Population: Time to RSV RNA Viral Load Being Undetectable | 12.27 days | Standard Deviation 2.958 |
Secondary
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
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
Population: Efficacy Population. Per the protocol, analyses were planned to be grouped by EDP-938 and placebo, rather than by dose. Only hospitalized participants who were not receiving oxygen at the time they received the first dose of study drug were included. In the Placebo arm, there were no hospitalized participants who were not receiving oxygen at the time they received the first dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: EDP-938 5mg/kg (≥ 28 Days to < 3 Months) | 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 | 0.51 days |