Clinical Trials Register

Summary
EudraCT Number:	2022-002215-29
Sponsor's Protocol Code Number:	EDP938-104
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2023-01-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2022-002215-29

A.3

Full title of the trial

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of EDP-938 in Non hospitalized Adults with Acute Respiratory Syncytial Virus Infection who are at High Risk for Complications

Randomizované, dvojitě zaslepené, placebem kontrolované klinické hodnocení fáze 2b, posuzující účinnost a bezpečnost přípravku EDP-938 u ne hospitalizovaných dospělých s akutní infekcí respiračním syncytiálním virem, u kterých je vysoké riziko komplikací

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

EDP938-104

A.5.4

Other Identifiers

Name:

IND

Number:

135874

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Enanta Pharmaceuticals, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Enanta Pharmaceuticals. Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Enanta Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	500 Arsenal Street
B.5.3.2	Town/ city	Watertown
B.5.3.3	Post code	MA 02472
B.5.3.4	Country	United States
B.5.4	Telephone number	+16177443226
B.5.6	E-mail	mgawryl@enanta.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	EDP-938
D.3.2	Product code	EDP-938
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EDP-938
D.3.9.1	CAS number	2070852-76-3
D.3.9.2	Current sponsor code	EDP-938
D.3.9.3	Other descriptive name	EDP-938
D.3.9.4	EV Substance Code	SUB214949
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Respiratory syncytial virus (RSV)

E.1.1.1

Medical condition in easily understood language

Respiratory syncytial virus is the leading cause of lower respiratory tract infection and presents a significant health challenge in small children, elderly, and people with weak immune systems

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061603
E.1.2	Term	Respiratory syncytial virus infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

- To evaluate the clinical efficacy of EDP-938 compared with placebo;
- To evaluate the antiviral activity of EDP-938 compared with placebo;
- To evaluate the PK of EDP-938;
- To evaluate the safety of EDP-938 compared with placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each subject must meet all of the following criteria to be enrolled into this study:
1. The subject has signed and dated the informed consent forms (ICFs).
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 (New York Heart Association [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. 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 investigational drug.
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. The subject has tested positive for RSV infection using a nucleic acid amplification test (NAAT; polymerase chain reaction [PCR] or other) on a nasal swab sample.
6. The subject has a body mass index ≥18 kg/m2 and ≤40 kg/m2.
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) levels >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. 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. 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.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.Subject is willing and able to adhere to the assessments, visit schedule, prohibitions, and restrictions, as described in this protocol.

E.4

Principal 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.
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;
3. The subject has a SARS-CoV-2 test result that is positive within 28 days prior to signing the Study ICF;
4. The subject is pregnant or nursing;
5. The subject has COPD GOLD Class IV (Venkatesan P., 2022);
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;
7. The subject has prior receipt of or is waiting to receive a bone marrow, stem cell, or solid organ transplantation;
8. The subject has a known positive human immunodeficiency virus infection, active hepatitis A virus infection, chronic hepatitis A 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.
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;
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;
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 CYP450 3A4 enzyme (see Section 5.8), within 14 days prior to signing the Study ICF;
12.The subject has received an RSV vaccine within 12 months prior to signing the Study ICF.
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;
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.
15. Known hypersensitivity to the investigational product or any of its excipients.
16. Receiving dialysis or have known severe renal impairment (ie., eGFR <30mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatine-based CKD-EPI formula).

E.5 End points

E.5.1

Primary end point(s)

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 33

E.5.2

Secondary end point(s)

Clinical efficacy:
1. Time to resolution of each separate RSV LRTD symptom as assessed by RiiQ™ symptom scale score;
2. Time to resolution of LRTD symptoms and 2 systemic symptoms (feeling feverish and fatigue [tiredness]) as assessed by RiiQ™ symptom scale score;
3. Time to resolution of all RSV symptoms as assessed by RiiQ™ symptom scale score;
4. Change from Baseline in severity of RSV LRTD symptoms through Day 33 as assessed by RiiQ™ symptom scale score;
5. Change from Baseline for RiiQ™ impact scale score through Day 33;
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. Time to no or mild impact of RSV disease on daily activities, emotions, and social relationships as assessed by RiiQ™ impact scale score;
8. Percentage of participants with post-baseline RSV-related complications;
9. Time to resolution of RSV infection symptoms as assessed by Patient Global Impression of Severity (PGI-S) scale score;
10.Time to improvement in RSV disease as assessed by Patient Global Impression of Change (PGI-C) scale score;
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.Time to return to usual health as assessed by ‘Adult Return to Usual Health’ question;
13.Time to return to usual activities as assessed by the ‘Adult Return to Usual Activities’ question;
14.Percentage of subjects with new antibiotic use, or new or increased use of bronchodilators, systemic or inhaled corticosteroids, or oxygen supplementation;
15.Duration of treatment-emergent use of antibiotics;
16.Duration of treatment-emergent new use or increased dose of bronchodilators or systemic or inhaled corticosteroids;
17.Duration of new or increased oxygen supplementation;
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.Percentage of subjects requiring hospitalization for RSV infection or other causes;
20.Duration of hospitalization for RSV infection or other causes;
21.Percentage of subjects requiring admission to intensive care unit (ICU) for RSV infection or other causes;
22.Duration of ICU stay for RSV infection or other causes;
23.Percentage of subjects requiring invasive or noninvasive mechanical ventilation;
24.Duration of invasive or noninvasive mechanical ventilation;
25.Duration of treatment-emergent new use or increased use of medications to treat CHF;
26.All-cause mortality.

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;
2. Percentage of subjects with RSV RNA viral load Targed Not Detected (TND) at any point during the study;
3. Time to RSV RNA viral load below TND;
4. RSV RNA viral load change from Baseline at Days 3, 5, 9, and 14;
5. Change in infectious RSV viral load over time by a quantitative cell-based infectivity assay.
• Pharmacokinetics:
o Plasma concentrations of EDP-938 and its metabolites (EP-024766, EP-024636, EP-024594, and EP-024595);
• 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).

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 33

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Colombia

Malaysia

Philippines

Taiwan

Brazil

Israel

Mexico

South Africa

United States

Bulgaria

Czechia

Germany

Netherlands

Poland

Slovakia

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient last visit (including Follow-up Period)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

164

F.4.2.2

In the whole clinical trial

180

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Best standard of care at investigator's discretion

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-01-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-09

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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