Respiratory Syncytial Virus Infections
Conditions
Brief summary
This was a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of EDP-938 in HCT recipients with acute RSV infection and symptoms of URTI.
Interventions
DRUGEDP-938
EDP-938 800mg Dose adjustments were made for subjects taking azole antifungals.
DRUGPlacebo
Subjects took EDP-938 matching placebo tablets once a day orally for 21 days
Sponsors
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Received an autologous HCT (within 6 months of signing ICF) or an allogeneic HCT (any time) using any conditioning regimen * Absolute lymphocyte count (ALC) \<500 cells/ µL in allogeneic HCT recipients. Absolute lymphocyte count (ALC) \<300 cells/ µL in autologous HCT recipients. * Laboratory confirmed RSV diagnosis from a respiratory sample obtained within 3 days before signing the ICF. * New onset of at least one of the following respiratory symptoms within 3 days before signing the ICF: nasopharyngeal discharge, nasopharyngeal congestion, sneezing, sinus congestion, sore throat, hoarseness, earache, cough, shortness of breath, respiratory wheeze, or worsening of one of these symptoms if present chronically (associated with a previously existing diagnosis \[eg, chronic rhinorrhea, chronic lung disease\]) in the 3 days before signing the ICF or at Screening. * No evidence of new abnormalities consistent with LRTI on a chest imaging (chest x-ray and/or computed tomography) performed in the 2 days before signing the ICF or at the Screening visit if there is no chest X-ray and/or computed tomography available in the 2 days before signing the ICF. * Oxygen saturation \>95% on room air. * A woman of childbearing potential who is sexually active with a male must agree to use two effective methods of contraception from the date of Screening until 30 days after her last dose of study drug. * A male subject who has not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use effective contraception from the date of Screening to 90 days after his last dose of study drug.
Exclusion criteria
* Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the Investigator. * Known to be concurrently infected with other respiratory viruses (eg, severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] or other coronavirus, influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus) within 7 days before signing the ICF, as determined by local testing. * Clinically significant viremia, bacteremia, or fungemia, or bacterial or fungal pneumonia within 2 weeks before signing the ICF that has not been adequately treated, as determined by the Investigator. * Known positive human immunodeficiency virus (HIV). * Any clinical manifestation resulting in QT prolongation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Who Develop Lower Respiratory Tract (LRTC) Complication | Day 1 through Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in RSV RNA Viral Load | Day 1 through Day 49 |
| Proportion of Subjects Progressing to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality | Day 1 through Day 49 |
| Safety as Measured the Number of Participants With at Least One Treatment-emergent Adverse Event | Day 1 through Day 49 |
| Plasma PK Concentrations of EDP-938 800mg | Day 1 Predose and Postdose, Day 4 Predose, Day 7 Predose and Postdose, Day 11 Predose, Day 16 Predose, Day 21 Predose and Postdose |
Countries
Argentina, Belgium, Brazil, Canada, China, Colombia, France, Greece, Israel, Italy, Mexico, Poland, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EDP-938 EDP-938: EDP-938 150/400/800mg
The EDP-938 doses were adjusted to account for inhibitory effects of Azole antifungals on hepatic metabolism, and EDP-938 doses of 150mg and 400mg; when EDP-938 is co-administered with azole antifungals that are strong or moderate CYP3A4 inhibitors, respectively, provide similar exposures to the 800mg dose | 5 |
| Placebo Placebo: Subjects took EDP-938 matching placebo tablets once a day orally for 21 days | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Placebo | Total | EDP-938 |
|---|---|---|---|
| Age, Continuous | 44.3 Years STANDARD_DEVIATION 15.99 | 44.3 Years STANDARD_DEVIATION 14.95 | 44.4 Years STANDARD_DEVIATION 15.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 3 / 4 |
| serious Total, serious adverse events | 4 / 5 | 0 / 4 |
Outcome results
Primary
Percentage of Subjects Who Develop Lower Respiratory Tract (LRTC) Complication
Time frame: Day 1 through Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EDP-938 | Percentage of Subjects Who Develop Lower Respiratory Tract (LRTC) Complication | 0 Participants |
| Placebo | Percentage of Subjects Who Develop Lower Respiratory Tract (LRTC) Complication | 1 Participants |
Secondary
Change From Baseline in RSV RNA Viral Load
Time frame: Day 1 through Day 49
Population: Six participants (3 in each treatment group) had detectable RSV by RT-qPCR at baseline and were included in the mITT by RT-qPCR analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EDP-938 | Change From Baseline in RSV RNA Viral Load | -7.072 RSV viral load (log10 copies/mL) | Standard Deviation 0.7738 |
| Placebo | Change From Baseline in RSV RNA Viral Load | -2.221 RSV viral load (log10 copies/mL) | Standard Deviation 6.8552 |
Secondary
Plasma PK Concentrations of EDP-938 800mg
Time frame: Day 1 Predose and Postdose, Day 4 Predose, Day 7 Predose and Postdose, Day 11 Predose, Day 16 Predose, Day 21 Predose and Postdose
Population: Pharmacokinetic (PK) Population, PK data for subjects who received EDP-938 800 mg doses. If more than 50% of subjects have post dose concentration values below the limit of quantification (BLQ), descriptive statistics are not presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 1 Predose | 0 ng/mL | Standard Deviation 0 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 1 Postdose | 1123.33 ng/mL | Standard Deviation 1028.899 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 4 Predose | 1610.00 ng/mL | Standard Deviation 175.784 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 7 Predose | 1342.33 ng/mL | Standard Deviation 411.554 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 11 Predose | 1176.67 ng/mL | Standard Deviation 204.287 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 16 Predose | 860.00 ng/mL | Standard Deviation 411.887 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 7 Postdose | 1394.33 ng/mL | Standard Deviation 493.504 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 21 Predose | 755.33 ng/mL | Standard Deviation 58.011 |
| EDP-938 | Plasma PK Concentrations of EDP-938 800mg | Day 21 Postdose | 1136.00 ng/mL | Standard Deviation 656.195 |
Secondary
Proportion of Subjects Progressing to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality
Time frame: Day 1 through Day 49
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EDP-938 | Proportion of Subjects Progressing to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality | 0 Participants |
| Placebo | Proportion of Subjects Progressing to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality | 0 Participants |
Secondary
Safety as Measured the Number of Participants With at Least One Treatment-emergent Adverse Event
Time frame: Day 1 through Day 49
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EDP-938 | Safety as Measured the Number of Participants With at Least One Treatment-emergent Adverse Event | 5 Participants |
| Placebo | Safety as Measured the Number of Participants With at Least One Treatment-emergent Adverse Event | 3 Participants |