E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus (RSV) |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory Syncytial Virus (RSV) can infect the lungs and windpipe. The infection could be particularly severe for small children, the elderly and in people with weak immune systems. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 |
Part 1 • To evaluate the PK of EDP-938 • To assess the safety and tolerability of EDP-938 Part 2 • To evaluate the antiviral activity of EDP-938 |
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E.2.2 | Secondary objectives of the trial |
Part 1 • To evaluate the antiviral activity of EDP-938 Part 2 • To assess the safety and tolerability of EDP-938 • To evaluate the PK of EDP-938 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female who is either: • born ≥37 weeks of gestation and is age ≥28 days to ≤36 months, defined at the time of randomization, or • born <37 weeks of gestation and is age ≥6 months to ≤36 months, defined at the time of randomization 2. Subjects diagnosed with RSV infection using an approved diagnostic assay, without known and/or documented coinfection by another respiratory pathogen (respiratory virus, fungus, or bacteria) 3. Subjects with signs of an acute respiratory illness (eg, fever [or symptoms of fever], cough, nasal congestion, runny nose, rapid breathing, shortness of breath, or wheezing) with onset ≤72 hours (for hospitalized subjects) and ≤48 hours (non-hospitalized subjects) before the time of signing the informed consent form (ICF) Note: Time of onset of symptoms is defined from the caregiver(s) estimated time of awareness of the first sign of respiratory infection 4. Have a calculated creatinine clearance rate not below the lower limit of normal (LLN) for the subject’s age as determined by the Schwartz equation (Schwartz & Work, 2009) at Screening 5. In the Investigator’s opinion, the subject’s caregiver understands and is able to comply with protocol requirements, instructions, and protocol-stated restrictions, and the subject is likely to complete the study as planned
Additional inclusion criterion for Part 1 Cohort 1 6. Subject is currently or is planned to be hospitalized as a consequence of RSV infection and is not anticipated to be discharged in less than 24 hours after enrollment |
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E.4 | Principal exclusion criteria |
1. Use of or anticipated need for intensive monitoring and associated medical care, eg admission to ICU or equivalent medical setting, requirement for mechanical ventilation, cardiopulmonary bypass, hemodialysis, or extracorporeal membrane oxygenation; or subjects who are not expected to survive the current illness 2. Subjects who have a medical history or a concurrent illness that in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject, or that could prevent, limit, or confound the protocol-specified assessments. Examples include liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic conditions 3. Subjects who are considered unable to take study drug orally, eg, as a consequence of acute respiratory distress, or unable to absorb study drug enterally 4. Subjects who have received blood products within 6 months of study drug administration 5. Height or weight outside of the 5th to 95th percentile for the respective ages, at the time of enrollment 6. Subjects with underlying immune deficiency, eg, from confirmed human immunodeficiency virus infection or use of an immunosuppressive medication except immunoglobulin A deficiency 7. Subjects who received (within 12 months before Screening) or who are currently on a waiting list for a bone marrow, stem cell, or solid organ transplant, or who received radiation or chemotherapy (within 12 months before screening) 8. Subjects who have had major surgery in the 6 weeks before randomization 9. Subject receiving chronic oxygen therapy at home before admission 10. Subjects who are being breastfed by a mother taking any of the excluded medications 11. Subjects whose mother received an investigational RSV vaccination while pregnant with the subject 12. Receipt of systemic antiviral, antibacterial, antifungal, or antimycobacterial therapy within 7 days of Screening 13. Subjects who received systemic medications (either chronically [more than 14 days] or within 21 days before randomization) that are known to modulate the host’s immune response or increase viral shedding, such as immunomodulatory therapies 14. Subjects who are receiving an investigational or approved medication that is intended to prevent or treat RSV infection (eg, ribavirin or palivizumab or other RSV specific monoclonal antibody) within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug, and/or is currently enrolled in a clinical trial of such a medication 15. Use of or intention to use any medication or supplement known to be a moderate or strong inducer or inhibitor of the cytochrome P450 3A4 enzyme within 14 days before the first dose of study drug 16. Subjects who are enrolled in another investigational drug or vaccine study 17. Known allergy/hypersensitivity or intolerance to EDP-938, placebo or their excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1 1) PK parameters of EDP-938 including area under the curve (AUC) and predose concentrations 2) Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited to, AEs, vital signs, and clinical laboratory results
Part 2 1) Daily change in RSV shedding in nasal swab samples determined using quantitative RT-PCR from before the first dose of study drug (Baseline) through treatment phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1 1) From Day 1 up to 10 hours post Day 5 dose 2) From baseline up to Day 28
Part 2 1) From baseline up to Day 14 |
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E.5.2 | Secondary end point(s) |
Part 1 1) AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse transcription polymerase chain reaction (RT-qPCR) 2) Daily change in RSV shedding in nasal swab samples determined using quantitative RT-PCR from before the first dose of study drug (Baseline) through treatment phase 3) Proportion of subjects with RSV RNA viral load below the limit of detection (LOD) in subjects receiving EDP-938 compared to placebo 4) Time to RSV RNA viral load being undetectable
Part 2 1) Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited to, AEs, vital signs, and clinical laboratory results 2) AUC for RSV RNA viral load measured in nasal swab samples by RT-qPCR 3) Proportion of subjects with RSV RNA viral load below the LOD in subjects receiving EDP-938 compared to placebo 4) Time to RSV RNA viral load being undetectable 5) PK parameters of EDP-938 including AUC and predose concentrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part 1 1) From baseline up to Day 14 2) From baseline up to Day 14 3) From baseline up to Day 14 4) From baseline up to Day 14
Part 2 1) From baseline up to Day 28 2) From baseline up to Day 14 3) From baseline up to Day 14 4) From baseline up to Day 14 5) From Day 1 up to 10 hours post Day 5 dose |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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 |
Australia |
Brazil |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
South Africa |
Taiwan |
United States |
Bulgaria |
Germany |
Poland |
Romania |
Spain |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |