E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory syncytial virus (RSV) |
Virus respiratorio sinciziale (RSV) |
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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 |
RSV è la principale causa di infezione del tratto respiratorio inferiore e rappresenta una sfida significativa per la salute nelle persone con un sistema immunitario debole |
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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 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of EDP-938 on the development of lower respiratory tract
complication (LRTC) in HCT subjects with an acute RSV URTI |
Valutare l’effetto di EDP-938 sullo sviluppo di complicanze del tratto respiratorio inferiore (Lower Respiratory Tract Complication, LRTC) in soggetti sottoposti ad HCT con una URTI acuta da RSV |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of EDP-938 on RSV viral load as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) of nasopharyngeal swab samples • To evaluate the effect of EDP-938 on progression to respiratory failure or all-cause mortality • To evaluate the progression of RSV infection using the InFLUenza Patient-Reported Outcome questionnaire • To evaluate the pharmacokinetics (PK) of EDP-938 and its metabolites • To evaluate the safety and tolerability of EDP-938 • To evaluate the effect of EDP-938 on infectious RSV viral load in nasopharyngeal swab samples as determined by a quantitative cell-based infectivity assay • To evaluate the relationship between the PK of EDP-938 and antiviral and clinical efficacy • To evaluate the incidence of major clinical events • To evaluate the length of hospital stay and time in the (ICU) • To evaluate the use of certain therapeutics • To evaluate the emergence of viral resistance with EDP-938 treatment |
• Valutare l’effetto di EDP-938 sulla carica virale di RSV misurata mediante reazione a catena della polimerasi a trascrizione inversa quantitativa (RT-qPCR) dei campioni di tampone nasofaringeo • Valutare l’effetto di EDP-938 sulla progressione verso l’insufficienza respiratoria o la mortalità per tutte le cause • Valutare la progressione dell’infezione da RSV utilizzando il questionario sugli esiti riferiti dal paziente relativo all’influenza (InFLUenza Patient-Reported Outcome, FLU-PRO) • Valutare la farmacocinetica (PK) di EDP-938 e dei suoi metaboliti • Valutare la sicurezza e la tollerabilità di EDP-938 • Valutare l’effetto di EDP-938 sulla carica virale infettiva di RSV in campioni di tampone nasofaringeo, come determinato mediante un test di infettività quantitativo basato su cellule
Si prega di fare riferimento agli endpoint secondari in inglese poichè per una question di spazio non era possibile elencarli tutti. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. An ICF signed and dated by the subject
2. Male or female individuals aged between 18 and 75 years, inclusive
3. Received an autologous or allogeneic HCT using any conditioning regimen
4. Absolute lymphocyte count (ALC) <500 cells/ µL
5. Laboratory confirmed RSV diagnosis from a respiratory sample obtained not more than 3 days prior signing the ICF. The RSV diagnosis can be determined by any validated laboratory method.
6. 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.
7. No evidence of new abnormalities consistent with LRTI on a chest X-ray performed in the 2 days before signing the ICF. If there is no chest X-ray available in the 2 days before signing the ICF, a chest X-ray must be obtained at the Screening visit.
8. Oxygen saturation =92% on room air.
9. A body mass index (BMI) =18 kg/m2 and =40 kg/m2.
10. Negative urine pregnancy test for women of childbearing potential as defined in inclusion criterion #11.
11. 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. Effective methods of contraception are defined as follows:
A condom for the male partner and at least one of the following for the female subject:
a. Intrauterine device
b. Occlusive cap (diaphragm or cervical/vault caps)
c. Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive
The above does not apply to a female subject who has a vasectomized male as the sole partner or who is of nonchildbearing potential (ie, physiologically incapable of becoming pregnant) as defined below:
a. Has had a complete hysterectomy =3 months before Screening,
b. Has had a bilateral oophorectomy (ovariectomy),
c. Has had a bilateral tubal ligation or fallopian tube inserts, or
d. Is postmenopausal (a total cessation of menses for at least 2 years; subjects with a cessation of menses between 1 to 2 years and a follicle-stimulating hormone [FSH] level of >35 mIU/mL will also be considered to be postmenopausal.)
12. 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. Effective contraception is defined as a condom and at least one of the following for a female partner:
a. Intrauterine device
b. Occlusive cap (diaphragm or cervical/vault caps)
c. Oral, injectable, implantable, transdermal, or intravaginal contraceptive
For a male subject who has had a vasectomy, use of a condom will still be required.
13. Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after his last dose of study drug.
14. Must be willing and able to adhere to the study assessments, visit schedules, prohibitions, and restrictions, as described in this protocol. |
Si prega di fare riferimento alla versione inglese dei criteri di inclusione sotto elencati |
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E.4 | Principal exclusion criteria |
1. Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the Investigator.
2. 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.
3. 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.
4. Pregnant or nursing female subjects.
5. History of drug and/or alcohol abuse that, in the opinion of the Investigator, may prevent adherence to protocol activities.
6. Known positive human immunodeficiency virus (HIV).
7. Heart disease: any congenital heart disease, congenital long QT syndrome, or any clinical manifestation resulting in QT interval prolongation. Chronic heart failure or ischemic heart disease or cardiac disease occurring as a consequence of neoplastic treatment and for which treatment medications have not added or increased in the last 3 months are not exclusionary.
8. Known malignant tumor that may interfere with the aims of the study or a subject completing the study.
9. Prior or planned ileal resection or bariatric surgery. Subjects who have undergone gastric surgeries that do not affect drug absorption (eg, gastric band or gastric sleeve procedures) will be allowed to participate if they are stable for at least 1 year before signing the ICF. Gastrectomy will be allowed if stable for at least 3 years before signing the ICF.
10. Estimated glomerular filtration rate by Modification of Diet in Renal Disease (MDRD) <50 mL/min as measured in the 3 days before signing the ICF or at Screening.
11. Alanine transferase >5 × ULN as measured in the 3 days before signing the ICF or at Screening.
12. Twelve-lead ECG demonstrating a QT interval corrected for heart rate according to Fridericia (QTcF) that is >500 milliseconds or other clinically relevant abnormalities as judged by the Investigator at Screening.
13. Use of or intention to use any medication or supplement known to be a moderate or strong inducer or inhibitor of the CYP3A4 enzyme (Section 5.8) within 14 days before signing the ICF.
14. Use of nonmarketed (according to region) or investigational agents, vaccines, biological products within 30 days or five half-lives before signing the ICF, whichever is longer.
15. Use of any investigational monoclonal anti-RSV antibodies within 4 months or five half-lives of signing the ICF, whichever is longer, or use of any investigational RSV vaccines after HCT.
16. Known hypersensitivity or allergy to EDP-938 or its excipients.
17. 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. |
Si prega di fare riferimento alla versione inglese dei criteri di esclusione sotto elencati |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of LRTC through Day 28 defined as at least one of the following as determined by the Endpoint Adjudication Committee
o Lower respiratory tract infection (LRTI) by RSV
o LRTI as secondary bacterial pneumonia
o LRTI by unusual pathogens
o LRTC of unknown etiology |
• Incidenza della LRTC fino al Giorno 28 definita dalla presenza di almeno una delle seguenti condizioni, come determinato dal Comitato di validazione degli endpoint o Infezione del tratto respiratorio inferiore (LRTI) da RSV o LRTI come polmonite batterica secondaria o LRTI da patogeni insoliti o LRTC di eziologia sconosciuta |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change in RSV RNA viral load from Baseline through Day 49 in nasopharyngeal swab samples by RT-qPCR
• Incidence of subjects who develop respiratory failure of any cause requiring mechanical ventilation (invasive or noninvasive) or all-cause mortality through Day 49
• Incidence of subjects with RSV RNA viral load below the lower limit of quantitation in subjects receiving EDP-938 through Day 49
• FLU-PRO questionnaire scores through Day 49
• Plasma PK concentrations of EDP-938 and its metabolites (EP-024636, EP-024594, and EP-024595)
• Safety endpoints include, but are not limited to, adverse events (AEs), serious adverse events (SAEs), vital sign measurements, pulse oximetry measurements, and clinical laboratory test results (including chemistry, hematology, and urinalysis) |
• Variazione della carica virale dell’RNA di RSV dal basale fino al Giorno 49 nei campioni di tampone nasofaringeo mediante RT-qPCR • Incidenza di soggetti che sviluppano insufficienza respiratoria per qualsiasi causa che richieda ventilazione meccanica (invasiva o non invasiva) o mortalità per tutte le cause fino al Giorno 49 • Incidenza di soggetti con carica virale dell’RNA di RSV al di sotto del limite inferiore di quantificazione nei soggetti che ricevono EDP-938 fino al Giorno 49 • Punteggi del questionario FLU-PRO fino al Giorno 49 • Concentrazioni PK plasmatiche di EDP-938 e dei suoi metaboliti (EP-024636, EP-024594 ed EP-024595) • Gli endpoint di sicurezza includono, a titolo esemplificativo ma non esaustivo, eventi avversi (EA), eventi avversi seri (Serious Adverse Event, SAE), misurazioni dei segni vitali, misurazioni pulsossimetriche e risultati dei test clinici di laboratorio (tra cui ematochimica, ematologia e analisi delle urine) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | Information not present in EudraCT |
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 |
Australia |
Brazil |
Canada |
Colombia |
Hong Kong |
Israel |
Korea, Republic of |
Mexico |
South Africa |
Taiwan |
Turkey |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
Argentina |
Greece |
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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
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Last patient last visit (including Follow-up Period) |
Ultima visita dell'ultimo paziente (compreso il periodo di follow-up) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |