A study to learn how well the drug EDP-938 works and how safe it is for non-hospitalized Adults with Acute Respiratory Syncytial Virus Infection, who are at High Risk for Complications

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Enanta Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

2 Feb 2023 → 23 Jun 2025

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Enanta Pharmaceuticals, Inc

External identifiers

EU CT number

2024-513861-38-00

EudraCT number

2022-002215-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Therapy

To evaluate the effect of EDP-938 compared with placebo on the progression of RSV infection by assessment of clinical symptoms.

Secondary objectives 4

1. To evaluate the clinical efficacy of EDP-938 compared with placebo;
2. To evaluate the antiviral activity of EDP-938 compared with placebo;
3. To evaluate the pharmacokinetics (PK) of EDP-938;
4. To evaluate the safety of EDP-938 compared with placebo.

Conditions and MedDRA coding

Respiratory syncytial virus (RSV)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. The subject has signed and dated the ICFs.
2. 2. 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).
3. 3. 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
4. 4. 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.
5. 5. The subject has tested positive for RSV infection using a NAAT (polymerase chain reaction [PCR] or other) on a nasal swab sample.
6. 6. The subject has a body mass index ≥18 kg/m2 and ≤40 kg/m2
7. 7. 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.
8. 8. 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.
9. 9. Male subject must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug.
10. 10. Female subject must agree to refrain from egg donation from the date of Screening until 30 days after their last dose of study drug.
11. 11. Subject is willing and able to adhere to the assessments, visit schedule, prohibitions, and restrictions, as described in this protocol.

Exclusion criteria 16

1. 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.
2. 10. 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.
3. 11. 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.
4. 12. The subject has received an RSV vaccine within 12 months prior to signing the Study ICF.
5. 13. 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;
6. 14. 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.
7. 2. 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.
8. 3. The subject has a SARS-CoV-2 test result that is positive within 28 days prior to signing the Study ICF.
9. 4. The subject is pregnant or nursing.
10. 5. The subject has COPD GOLD Class IV [Venkatesan P., 2022];
11. 6. 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.
12. 7. The subject has prior receipt of or is waiting to receive a bone marrow, stem cell, or solid organ transplantation.
13. 8. 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.
14. 9. 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.
15. 15. Known hypersensitivity to the investigational product or any of its excipients.
16. 16. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to resolution of RSV Lower Respiratory Tract Disease (LRTD) symptoms (cough, short of breath, wheezing, coughing up phlegm [sputum]) as assessed by the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) symptom scale through Day 33

Secondary endpoints 33

1. Clinical efficacy: 1. Time to resolution of each separate RSV LRTD symptom as assessed by RiiQ™ symptom scale score;
2. 2. Time to resolution of LRTD symptoms and 2 systemic symptoms (feeling feverish and fatigue [tiredness]) as assessed by RiiQ™ symptom scale score;
3. 3. Time to resolution of all RSV symptoms as assessed by RiiQ™ symptom scale score;
4. 4. Change from Baseline in severity of RSV LRTD symptoms through Day 33 as assessed by RiiQ™ symptom scale score;
5. 5. Change from Baseline for RiiQ™ impact scale score through Day 33;
6. 6. Time to resolution of Upper Respiratory Tract Disease (sore throat and nasal congestion), LRTD, and 2 systemic symptoms through Day 33 as assessed by RiiQ™ symptom scale score;
7. 7. Time to no or mild impact of RSV disease on daily activities, emotions, and social relationships as assessed by RiiQ™ impact scale score;
8. 8. Percentage of participants with post-baseline RSV-related complications;
9. 9. Time to resolution of RSV infection symptoms as assessed by Patient Global Impression of Severity (PGI-S) scale score;
10. 10. Time to improvement in RSV disease as assessed by Patient Global Impression of Change (PGI-C) scale score;
11. 11. Change from Baseline for Health-Related Quality of Life (HRQOL) through Day 33 as assessed by EuroQol 5 Dimensions 5 Levels (EQ--5D--5L) questionnaire
12. 12. Time to return to usual health as assessed by ‘Adult Return to Usual Health’ question;
13. 13. Time to return to usual activities as assessed by the ‘Adult Return to Usual Activities’ question;
14. 14. Percentage of subjects with new antibiotic use, or new or increased use of bronchodilators, systemic or inhaled corticosteroids, or oxygen supplementation;
15. 15. Duration of treatment-emergent use of antibiotics;
16. 16. Duration of treatment-emergent new use or increased dose of bronchodilators or systemic or inhaled corticosteroids;
17. 17. Duration of new or increased oxygen supplementation;
18. 18. Percentage of subjects with unscheduled medically attended visits (i.e., outpatient clinic, urgent care center, or emergency room visits) for RSV infection or other causes;
19. 19. Percentage of subjects requiring hospitalization for RSV infection or other causes;
20. 20. Duration of hospitalization for RSV infection or other causes;
21. 21. Percentage of subjects requiring admission to intensive care unit (ICU) for RSV infection or other causes;
22. 22. Duration of ICU stay for RSV infection or other causes;
23. 23. Percentage of subjects requiring invasive or noninvasive mechanical ventilation
24. 24. Duration of invasive or noninvasive mechanical ventilation;
25. 25. Duration of treatment-emergent new use or increased use of medications to treat CHF
26. 26. All-cause mortality.
27. • Antiviral activity: 1. RSV RNA viral load area under the curve (AUC) measured in nasopharyngeal swab samples by quantitative reverse transcription polymerase chain reaction (RT-qPCR) from Baseline at Days 3, 5, 9, and 14;
28. 2. Percentage of subjects with RSV RNA viral load Target Not Detected (TND) at any point during the study;
29. 3. Time to RSV RNA viral load below TND;
30. 4. RSV RNA viral load change from Baseline at Days 3, 5, 9, and 14;
31. 5. Change in infectious RSV viral load over time by a quantitative cell-based infectivity assay.
32. • Pharmacokinetics: o Plasma concentrations of EDP-938 and its metabolites (EP-024766, EP-024636, EP-024594, and EP-024595);
33. Safety: o Safety endpoints include, but are not limited to, adverse events (AEs; including serious adverse events [SAEs], severe AEs, and AEs leading to discontinuation of the study drug), and clinically significant changes from baseline in vital sign measurements, pulse oximetry measurements, electrocardiograms (ECGs), and clinical laboratory test results (including chemistry and hematology).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Enanta Pharmaceuticals Inc.

Sponsor organisation

Enanta Pharmaceuticals Inc.

Address

4 Kingsbury Avenue

City

Watertown

Postcode

02472-5789

Country

United States

Scientific contact point

Organisation

Enanta Pharmaceuticals Inc.

Contact name

Maria Gawryl

Public contact point

Organisation

Enanta Pharmaceuticals Inc.

Contact name

Maria Gawryl

Third parties 10

Locations

6 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications