E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus (RSV) Infection of the lower respiratory tract. |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory Syncytial Virus (RSV) Infection is a respiratory virus that infects the lungs and breathing passages. |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039247 |
E.1.2 | Term | RSV infection |
E.1.2 | System Organ Class | 100000004862 |
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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 presatovir on RSV viral load in autologous or allogeneic HCT recipients with an acute RSV LRTI |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of presatovir on being free of any supplemental oxygen, and rates of respiratory failure and all cause mortality - To evaluate the PK, safety, and tolerability of presatovir |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females 18 to 75 years of age 2. Received an autologous or allogeneic HCT using any conditioning regimen 3. Evidence of new abnormalities on chest X-ray obtained < 48 hours prior to Screening, determined to be consistent with LRTI by the local radiologist, relative to the most recent chest X-ray. If chest X-ray is not available, a chest X-ray must be obtained for Screening. 4. Documented RSV in both the upper (eg, nasal swab, nasopharyngeal swab, nasal wash) and lower (eg, induced sputum, BAL, lung biopsy, but not spontaneous sputum) respiratory tract as determined by local testing (eg, PCR, DFA, RVP assay, or culture). All samples must have been collected ≤ 6 days prior to Day 1 or as determined at Screening as per Section 6.1.1. 5. An informed consent document signed and dated by the subject or a legal guardian of the subject and investigator or his/her designee. In Sweden ICFs signed by legal guardian must also be signed by a close relative of the subject. 6. A negative urine or serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal) 7. Male and female subjects of childbearing potential must agree to contraceptive requirements as described in Appendix 5 8. Willingness to complete necessary study procedures and have available a working telephone or email |
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E.4 | Principal exclusion criteria |
Related to concomitant or previous medication use: 1. Use of non-marketed (according to region) investigational agents within 30 days, OR use of any investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT 2. Use of a moderate or strong cytochrome P450 enzyme (CYP) inducer including but not limited to rifampin, St. John’s Wort, carbamazepine, and phenytoin, efavirenz, bosentan, etravirine, modafinil, and nafcillin, within 2 weeks prior to the first dose of IMP Related to medical history: 3. Pregnant, breastfeeding, or lactating females 4. Unable to tolerate nasal sampling required for this study, as determined by the investigator 5. Known history of HIV/AIDS with a CD4 count <200 cells/μL within the last month 6. History of drug and/or alcohol abuse that, in the opinion of the investigator, may prevent adherence to study activities Related to medical conditions: 7. Requiring invasive mechanical ventilation at the time of randomization 8. Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus or coronavirus), from the lower respiratory tract sample as determined by local testing 9. Clinically significant bacteremia or fungemia within 7 days prior to Screening that has not been adequately treated, as determined by the investigator 10. Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated, as determined by the investigator 11. Excessive nausea/vomiting at screening, as determined by the investigator, or an inability to swallow pills that precludes oral administration of the IMP (for subjects without an NG tube in place) 12. Any condition which, in the opinion of the investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints Related to allergies: 13. Known hypersensitivity or allergy to the IMP, its metabolites, or formulation excipients (microcrystalline cellulose, mannitol, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol and talc) 14. History of hypersensitivity, anaphylactic reaction, Stevens-Johnson Syndrome, or toxic epidermal necrolysis response to sulfa drugs Related to laboratory results: 15. Creatinine clearance < 30 mL/min (calculated using the Cockcroft-Gault method) 16. Clinically significant AST/ALT, as determined by the investigator 17. Clinically significant TB, as determined by the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time-weighted average change in nasal RSV viral load (log10 copies/mL) from Baseline (Day 1) to Day 9 as measured by RT-qPCR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 to day 9 (daily measure) |
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E.5.2 | Secondary end point(s) |
- Number of supplemental O2 free days through Day 28 - Proportion of subjects developing respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) through Day 28 - Proportion of all-cause mortality among subjects through Day 28 |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Australia |
Canada |
France |
Germany |
Israel |
Korea, Republic of |
Netherlands |
Poland |
Sweden |
Taiwan |
United Kingdom |
United States |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |