Evaluation of EDP-938 (Zelicapavir) Efficacy and Safety in Non-Hospitalized Adults with Acute Respiratory Syncytial Virus Infection at High Risk for Complications

Trial ID: 2024-513861-38-00
Protocol: EDP 938-104
Sponsor: Enanta Pharmaceuticals Inc.

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Diseases & Conditions

Respiratory syncytial virus infection

Objectives

The primary objective of this study is to evaluate the effect of **EDP-938** compared with placebo on the progression of **Respiratory Syncytial Virus (RSV)** infection by assessing clinical symptoms. This is clinically relevant as it aims to determine the potential of EDP-938 in mitigating the progression of RSV, a significant cause of respiratory illness, particularly in high-risk populations.

Secondary objectives include:

Evaluating the clinical efficacy of EDP-938 compared with placebo.
Assessing the antiviral activity of EDP-938 compared with placebo.
Evaluating the pharmacokinetics (PK) of EDP-938.
Assessing the safety of EDP-938 compared with placebo.

Participants

The clinical trial investigating the effects of EDP-938 on the progression of **Respiratory syncytial virus (RSV)** infection involves a total of 58 participants. The study population comprises both male and female adults, aged 18 years and older, with a predisposition to complications following RSV infection. This includes individuals aged 65 years and above, as well as those with conditions such as congestive heart failure, asthma, or chronic obstructive pulmonary disease. Participants were selected based on the presence of new or worsening respiratory symptoms consistent with an RSV infection, confirmed by a positive test result. The trial includes individuals with a body mass index between 18 kg/m² and 40 kg/m². Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to specific birth control measures if applicable. The trial population includes vulnerable groups, ensuring a comprehensive assessment of the investigational drug's efficacy across diverse health statuses.

Plans and Procedures

The clinical trial is a **Phase 2b**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **EDP-938** in non-hospitalized adults with acute **respiratory syncytial virus (RSV)** infection who are at high risk for complications. The trial aims to assess the effect of EDP-938 compared with placebo on the progression of RSV infection by evaluating clinical symptoms. The study is expected to commence recruitment on March 1, 2024, and conclude by December 30, 2024.

Participants will be randomly assigned to receive either EDP-938 or placebo, administered orally in the form of coated tablets. The maximum daily dose of EDP-938 is 800 mg, with a total dose not exceeding 4000 mg over a treatment period of up to 5 days. The trial will include several key visits: an initial screening visit to confirm eligibility, multiple follow-up visits to monitor progress and collect data, and a final end-of-study visit to assess outcomes and gather final data points.

The inclusion criteria require participants to be adults aged 18 years or older, with conditions predisposing them to complications from RSV, such as being aged 65 years or older, having congestive heart failure, asthma, or chronic obstructive pulmonary disease. Participants must have a new onset or worsening of symptoms consistent with a respiratory tract infection within 72 hours prior to the first dose and must test positive for RSV infection. The study will exclude individuals who do not meet these criteria or who have conditions that could interfere with the study's objectives.

The primary endpoint is the time to resolution of RSV lower respiratory tract disease symptoms, assessed through Day 33 using the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) symptom scale. Secondary endpoints include various measures of clinical efficacy, antiviral activity, and safety, such as changes in symptom severity, time to resolution of symptoms, and the impact on daily activities. Safety endpoints will include monitoring for adverse events and clinically significant changes in vital signs and laboratory test results.

Participant involvement is expected to last until the end of the study period, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or the occurrence of adverse events that necessitate discontinuation. The study is designed to ensure rigorous data collection and analysis to evaluate the potential benefits and risks of EDP-938 in the target population.

Treatment

The clinical trial involves the administration of **EDP-938**, an investigational medication, to evaluate its efficacy and safety in non-hospitalized adults with acute **Respiratory Syncytial Virus (RSV)** infection who are at high risk for complications. **EDP-938** is formulated as a coated tablet and contains the active substance **Zelicapavir**. The pharmaceutical form is a coated tablet, and the route of administration is oral. The dosing regimen for **EDP-938** involves a maximum daily dose of 800 mg, with a total maximum dose of 4000 mg over a treatment period of up to 5 days. The medication is manufactured by Enanta Pharmaceuticals, Inc., and is classified as a chemical substance.

In addition to the experimental treatment, the study includes the use of **EDP-938 Placebo tablets** as a comparator. The placebo tablets are designed to match the appearance of the **EDP-938** coated tablets but do not contain the active substance **Zelicapavir**. The placebo is administered orally, following the same dosing schedule as the active treatment, to maintain the double-blind nature of the study. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol.

Efficacy

The efficacy of EDP-938 in treating acute **Respiratory Syncytial Virus** (RSV) infection will be assessed through a series of primary and secondary endpoints. The primary endpoint is the time to resolution of RSV Lower Respiratory Tract Disease (LRTD) symptoms, including cough, shortness of breath, wheezing, and coughing up phlegm, as evaluated by the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) symptom scale through Day 33.

Secondary endpoints include various measures of clinical efficacy, such as the time to resolution of each separate RSV LRTD symptom, the time to resolution of LRTD symptoms along with two systemic symptoms (feeling feverish and fatigue), and the time to resolution of all RSV symptoms, all assessed by the RiiQ™ symptom scale score. Additional secondary endpoints involve changes from baseline in the severity of RSV LRTD symptoms and the RiiQ™ impact scale score through Day 33, as well as the time to no or mild impact of RSV disease on daily activities, emotions, and social relationships.

Antiviral activity will be evaluated by measuring the RSV RNA viral load area under the curve (AUC) in nasopharyngeal swab samples using quantitative reverse transcription polymerase chain reaction (RT-qPCR) from baseline at Days 3, 5, 9, and 14. The percentage of subjects with RSV RNA viral load Target Not Detected (TND) at any point during the study, the time to RSV RNA viral load below TND, and changes in infectious RSV viral load over time by a quantitative cell-based infectivity assay will also be assessed.

Pharmacokinetic assessments will include plasma concentrations of EDP-938 and its metabolites. Safety endpoints will encompass adverse events, including serious adverse events, severe adverse events, and adverse events leading to discontinuation of the study drug, as well as clinically significant changes from baseline in vital sign measurements, pulse oximetry measurements, electrocardiograms (ECGs), and clinical laboratory test results.

Inclusion and Exclusion Criteria

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Inclusion Criteria

The subject has signed and dated the ICFs.
The subject is a male or female adult at least 18 years of age, who has at least one of the following conditions that predispose them to complications after RSV infection: a. Age ≥65 years; b. CHF (NYHA Class I to IV)[New York Heart Association Criteria Committee, 1994]; c. Asthma; d. COPD . Note: Subjects with COPD and a diagnosis of alpha-1-anti-trypsin deficiency must have a transient elastography indicating no evidence of significant liver fibrosis (i.e., >7 kPa) or cirrhosis (i.e., >11 kPa).
The subject has a new onset of any of the following symptom(s) or worsening of preexisting symptom(s) consistent with a respiratory tract infection no more than 72 hours prior to the administration of the first dose of study drug: feeling feverish, headache, neck pain, fatigue, loss of appetite, interrupted sleep, body aches, sore throat, nasal congestion, cough, cough with phlegm, wheezing, or short of breath. Note: The duration of new onset of symptom(s) or worsening of pre-existing symptom(s) is to be measured from the estimated time of onset of the first symptom to the anticipated time of dosing with the study drug
The subject reports at least 2 of the following symptoms, one of which must be reported as at least 'moderate' severity by the subject using the RiiQ™: cough, cough with phlegm, wheezing, or short of breath.
The subject has tested positive for RSV infection using a NAAT (polymerase chain reaction [PCR] or other) on a nasal swab sample.
The subject has a body mass index ≥18 kg/m2 and ≤40 kg/m2
A heterosexually active female subject must agree to use 2 effective birth control methods for the duration of the study and for 30 days after the last dose of study drug, or be surgically sterile for at least 6 months or postmenopausal; subjects who are <2 years postmenopausal will require a confirmatory serum follicle stimulating hormone (FSH) level >35 IU/mL. Note: Effective birth control methods include male or female condom (may not be used together), intrauterine device (IUD), or systemic hormonal (i.e., oral, injectable, implantable, transdermal, or intravaginal) contraception associated with the inhibition of ovulation started a minimum of 2 weeks prior to signing the Study ICF: a. A heterosexually active female subject with a single male partner who has been vasectomized is not required to use another effective birth control method. b. A female subject who practices sexual abstinence is not required to use another effective birth control method.
A heterosexually active male subject and their female partner(s) of childbearing potential must agree to use 2 effective birth control methods for the duration of the study and for 90 days after the last dose of study drug. Note: Effective birth control methods include male or female condom (may not be used together), systemic hormonal contraception associated with the inhibition of ovulation started a minimum of 2 weeks prior to signing the Study ICF, or IUD. a. A vasectomized heterosexually active male subject with a single female partner is not required to use another effective birth control method; b. Male subjects who practice sexual abstinence are not required to use another effective birth control method.
Male subject must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug.
Female subject must agree to refrain from egg donation from the date of Screening until 30 days after their last dose of study drug.
Subject is willing and able to adhere to the assessments, visit schedule, prohibitions, and restrictions, as described in this protocol.

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Exclusion Criteria

A subject will not be eligible to participate in the study if they meet any of the following criteria: 1. The subject has an anticipated need for hospitalization within 24 hours of signing the Study ICF. Note: Emergency room or hospital observation status for an anticipated duration of less than <24 hours is not considered as hospitalization.
The subject has any of the following cardiac conditions: any congenital heart disease, congenital long QT syndrome, or any clinical manifestation resulting in QT interval prolongation.
The subject has use of or intention to use excluded or contraindicated medication(s) or supplements, including any medication known to be a moderate or strong inducer or inhibitor of the cytochrome P450 3A4 enzyme (see Section 5.8) within 14 days prior to signing the Study ICF.
The subject has received an RSV vaccine within 12 months prior to signing the Study ICF.
The subject has received any investigational agent within 30 days (or 5 half-lives of that investigational agent, whichever is longer) prior to the first dose of study drug;
The subject has a history of or is 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.
The subject has concomitant respiratory infections that are viral (other than RSV but including influenza), bacterial, or fungal, including systemic bacterial or fungal infections, within 7 days prior to signing the Study ICF.
The subject has a SARS-CoV-2 test result that is positive within 28 days prior to signing the Study ICF.
The subject is pregnant or nursing.
The subject has COPD GOLD Class IV [Venkatesan P., 2022];
The subject has a malignant tumor or history of malignancy that may interfere with the aims of the study or a subject completing the study.
The subject has prior receipt of or is waiting to receive a bone marrow, stem cell, or solid organ transplantation.
The subject has a known positive human immunodeficiency virus infection, active hepatitis A virus infection, chronic hepatitis B virus infection, and/or current hepatitis C virus (HCV) infection; subjects with a history of HCV infection who have achieved a documented sustained virologic response 12 weeks after completion of HCV therapy may be enrolled.
The subject has a history of chronic liver disease (e.g., hemochromatosis, Wilson’s disease, cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, and/or alcoholic liver disease); a history of active biliary disease (e.g., primary sclerosing cholangitis); or a history of portal hypertension. A diagnosis of hepatic steatosis (fatty liver) is not exclusionary.
Known hypersensitivity to the investigational product or any of its excipients.
Receiving dialysis or have known severe renal impairment (ie., eGFR <30 mL/min/ 1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	01 Mar 2024	16
Czechia	Not Recruiting	01 Mar 2024	3
The Netherlands	Not Recruiting	01 Mar 2024	—
Poland	Not Recruiting	01 Mar 2024	1
Slovakia	Not Recruiting	01 Mar 2024	1
Spain	Not Recruiting	01 Mar 2024	12
Netherlands	—	—	20