Respiratory Syncytial Virus
Conditions
Keywords
RSV
Brief summary
This was a randomized, double-blind, placebo-controlled, multicentre, phase 2 study to evaluate the efficacy, safety and tolerability of orally administered EDP-938 in adults with RSV infection.
Detailed description
Subjects (aged 18 to 75 years, inclusive) with up to 48 hours of upper respiratory tract infection (URTI) symptoms who tested positive for respiratory syncytial virus (RSV) and negative for influenza virus by rapid testing (ie, Rapid Viral Screen). Subjects with stable asthma or chronic obstructive pulmonary disease (COPD) were allowed in the study. Eighty-two (82) subjects were enrolled in this Phase 2b, randomized, double-blind, placebo-controlled, multicentre study of EDP-938 administered orally for the treatment of acute URTI with confirmed RSV infection in ambulatory adult subjects. For each subject, the duration of study participation was approximately 2 weeks and consisted of 3 periods: Screening (occurs on Day1), Treatment (5 days), and Follow-up (9 days after last dose).
Interventions
DRUGEDP-938
Four tablets daily for 5 days
DRUGPlacebo
Four tablets daily for 5 days
Sponsors
PPD Development, LP
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
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* An informed consent document must be signed and dated by the subject * Male or female individuals aged 18 to 75 years, inclusive. * Up to 48 hours of URTI symptoms with at least one of the following symptoms: Nasal discharge, nasal congestion, malaise/tiredness, headache, sinus congestion, sneezing, sore throat, hoarseness, cough, shortness of breath, respiratory wheeze, earache, and/or symptoms of fever. * Positive for RSV infection and negative for influenza virus based on rapid diagnostic. * Must be willing and able to adhere to the study assessments, visit schedules, prohibitions, and restrictions, as described in this protocol.
Exclusion criteria
* SARS-CoV-2 positive within 28 days of Screening or at Screening following signature of full ICF. * Clinical evidence of a lower respiratory tract infection, as determined by the Investigator. * Anticipated need for hospitalization or emergency room care within 24 hours of Screening. * Receipt of systemic antiviral, antibacterial, antifungal, or antimycobacterial therapy within 7 days of Screening and for the duration of the study * Awareness of concomitant respiratory infections that are viral (other than RSV), bacterial, or fungal, including systemic bacterial or fungal infections, within 7 days of Screening. * Frailty scale score ≥4 at Screening. * History of chronic liver disease (eg, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, autoimmune hepatitis, nonalcoholic steatohepatitis, and/or alcoholic liver disease); a history of biliary disease (eg, primary sclerosing cholangitis, cholecystitis, choledocholithiasis); or a history of portal hypertension. A diagnosis of hepatic steatosis (fatty liver) is not exclusionary. * Heart disease: any congenital heart disease, acute or chronic heart failure, ischemic heart disease, congenital long QT syndrome, or any clinical manifestation resulting in QT interval prolongation. * Neurological and neurodevelopmental disorders (including disorders of the brain, spinal cord, peripheral nerve, and muscle, eg, cerebral palsy, epilepsy \[seizure disorders\], stroke, muscular dystrophy, or spinal cord injury). * Malignant tumor or history of malignancy that may interfere with the aims of the study or a subject completing the study. * Prior receipt or the subject is waiting to receive a bone marrow, stem cell, or solid organ transplantation. * Diagnosis of cystic fibrosis. * Known positive human immunodeficiency virus, active hepatitis A virus infection, chronic hepatitis B virus infection, and/or current or treated hepatitis C virus infection. * Prior or planned ileal resection or bariatric surgery. * Pregnant or nursing female subjects. * History of alcohol addiction or current heavy alcohol use defined as: \>14 standard drinks per week and/or ≥4 standard drinks per occasion for males and \>7 standard drinks per week and/or ≥3 standard drinks per occasion for females. A standard drink is 12 oz of beer (5% alcohol), 5 oz table wine (12% alcohol), or 1.5 oz of spirits (40% alcohol). * Known or suspected, in the opinion of the Investigator, renal disease or renal impairment. * Twelve-lead ECG demonstrating a QT interval corrected for heart rate according to Fridericia (QTcF) that is \>500 msec or other clinically relevant abnormalities as judged by the Investigator at Screening. * Use of or intention to use excluded or contraindicated medication(s) or supplements, including any medication known to be a moderate or potent inducer or inhibitor of the cytochrome P450 3A4 enzyme, within 14 days prior to Screening and for the duration of the study. * Receipt of ≥14 days of systemic immunomodulator therapy (eg, oral corticosteroids) within 3 months of Screening. * Prior to the first dose of study drug and during study participation, the subject has received any vaccine, investigational agent, or biological product within 30 days or 5 times the half-life, whichever is longer. Note: Influenza vaccination within 7 days of Screening is allowed. * Use of St John's wort within 28 days prior to the first dose of study drug and for the duration of the study. * History of or currently experiencing a medical condition or any other finding (including laboratory test results) that, in the opinion of the Investigator, might confound the results of the study; pose an additional risk in administering study drug to the subject; could prevent, limit, or confound the protocol-specified assessments; or deems the subject unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Symptom Score (TSS) Area Under the Curve (AUC) | Day 1 through Day 14 | Assessed by the RSV Symptom Diary, including 13 items assessing the severity of RSV-related signs and symptoms. The diary uses a 4-point scale that consists of grading symptoms on a scale of 0 to 3 for each item, where Grade 0 is Absent, Grade 1 is Noticeable, Grade 2 is Bothersome but not preventing activity, and Grade 3 is Bothersome and interfering with activities. TSS is derived daily by summing of the 13 observed symptom grade values from Day 1 through Day 14 to generate the curve for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV RNA Viral Load Area Under the Curve (AUC) | Day 1 through Day 14 | RSV RNA viral load as measured in nasopharyngeal swab samples by RT-qPCR on Days 1 (Baseline, time 0), 3, 5, 9, and 14 to generate curve for analysis. |
| Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Days 3, 5, 9 and 14 | Proportion of patients that have undetectable RSV RNA by qRT-PCR at Days 3, 5, 9 and 14. |
| Number of Participants With Adverse Events | Day 1 through Day 14 | — |
Countries
Argentina, Bulgaria, New Zealand, Poland, South Africa, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EDP-938 Subjects will take EDP-938 tablets (800 mg) once a day orally for 5 days
EDP-938: Four tablets daily for 5 days | 40 |
| Placebo Subjects will take EDP-938 matching placebo tablets once a day orally for 5 days
Placebo: Four tablets daily for 5 days | 41 |
| Total | 81 |
Baseline characteristics
| Characteristic | Placebo | Total | EDP-938 |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 14.14 | 47.4 years STANDARD_DEVIATION 14.28 | 47.0 years STANDARD_DEVIATION 14.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 16 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 65 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 36 Participants | 71 Participants | 35 Participants |
| Sex: Female, Male Female | 26 Participants | 51 Participants | 25 Participants |
| Sex: Female, Male Male | 15 Participants | 30 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 41 |
| other Total, other adverse events | 11 / 40 | 11 / 41 |
| serious Total, serious adverse events | 0 / 40 | 0 / 41 |
Outcome results
Primary
Total Symptom Score (TSS) Area Under the Curve (AUC)
Assessed by the RSV Symptom Diary, including 13 items assessing the severity of RSV-related signs and symptoms. The diary uses a 4-point scale that consists of grading symptoms on a scale of 0 to 3 for each item, where Grade 0 is Absent, Grade 1 is Noticeable, Grade 2 is Bothersome but not preventing activity, and Grade 3 is Bothersome and interfering with activities. TSS is derived daily by summing of the 13 observed symptom grade values from Day 1 through Day 14 to generate the curve for analysis.
Time frame: Day 1 through Day 14
Population: The mITT population included 66 subjects, comprised of all randomized subjects positively diagnosed using the central RT-PCR test who received at least one dose of the assigned study drug or placebo. Per SAP, one subject in the EDP-938 group with only baseline data was excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-938 | Total Symptom Score (TSS) Area Under the Curve (AUC) | RSV A | 93.64 days x Score | Standard Deviation 97.18 |
| EDP-938 | Total Symptom Score (TSS) Area Under the Curve (AUC) | RSV B | 73.75 days x Score | Standard Deviation 66.652 |
| Placebo | Total Symptom Score (TSS) Area Under the Curve (AUC) | RSV A | 62.53 days x Score | Standard Deviation 40.31 |
| Placebo | Total Symptom Score (TSS) Area Under the Curve (AUC) | RSV B | 78.34 days x Score | Standard Deviation 58.051 |
Secondary
Number of Participants With Adverse Events
Time frame: Day 1 through Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EDP-938 | Number of Participants With Adverse Events | 11 Participants |
| Placebo | Number of Participants With Adverse Events | 11 Participants |
Secondary
Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD)
Proportion of patients that have undetectable RSV RNA by qRT-PCR at Days 3, 5, 9 and 14.
Time frame: Days 3, 5, 9 and 14
Population: Based on subjects positively diagnosed using the central RT-PCR test and with detectable viral load at baseline and non-missing viral load assessment at the respective visit and is used as a denominator in the percentage calculation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EDP-938 | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 9 | 15 Participants |
| EDP-938 | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 5 | 12 Participants |
| EDP-938 | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 14 | 26 Participants |
| EDP-938 | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 3 | 5 Participants |
| Placebo | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 14 | 23 Participants |
| Placebo | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 5 | 5 Participants |
| Placebo | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 9 | 11 Participants |
| Placebo | Number of Subjects With RSV RNA Viral Load Below Limit of Detection (LOD) | Day 3 | 2 Participants |
Secondary
RSV RNA Viral Load Area Under the Curve (AUC)
RSV RNA viral load as measured in nasopharyngeal swab samples by RT-qPCR on Days 1 (Baseline, time 0), 3, 5, 9, and 14 to generate curve for analysis.
Time frame: Day 1 through Day 14
Population: The mITT population included 66 subjects, comprised of all randomized subjects positively diagnosed using the central RT-PCR test who received at least one dose of the assigned study drug or placebo. Per SAP, one subject in the placebo group and two subjects in the EDP-938 group with only baseline data were excluded from analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EDP-938 | RSV RNA Viral Load Area Under the Curve (AUC) | 37.00 days x log10 copies/mL | Standard Deviation 24.003 |
| Placebo | RSV RNA Viral Load Area Under the Curve (AUC) | 46.96 days x log10 copies/mL | Standard Deviation 21.002 |