E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10022005 |
E.1.2 | Term | Influenza viral infections |
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 |
The primary objectives of the study is to evaluate the time to resolution of influenza symptoms in adults with acute uncomplicated seasonal influenza A following administration of VX-787, with and without concomitant oseltamivir. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate:
• Safety and tolerability of administration of VX-787 with and without concurrent oseltamivir in adults with acute uncomplicated seasonal influenza A
• Antiviral effect, as measured by viral titer in nasal secretions, of administration of 2 dose levels of VX-787 as a monotherapy and of 1 dose level of VX-787 in combination with oseltamivir in adults with acute uncomplicated seasonal influenza A
• Change in the duration and severity of clinical symptoms
• Pharmacokinetics of VX-787, administered as a monotherapy and in combination with oseltamivir
• Assessment of viral sequences for changes that may be associated with resistance to VX-787 and/or oseltamivir |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part A:
• Willing and able to comply with nasopharyngeal swabs
• Subjects have an oral temperature of ≥38°C (100.4°F) within the prior 24 hours and at least 1 respiratory and 1 systemic symptom
Part B:
• Willing and able to comply with study requirements including treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
• Subjects have a documented oral temperature of ≥38°C (100.4°F) during the screening visit unless antipyretic medication had been administered within the past 6 hours, in which case a normal temperature at screening is acceptable, so long as the patient had a fever >38°C at some time prior to taking the medication, and at least 1 respiratory and 1 systemic symptom, both scored as at lease “moderate” when self-assessed with a symptom assessment scale.
• The onset of flu-like symptoms must be ≤48 hours before receiving study drug.
• Subjects must be positive for influenza A with a rapid influenza diagnostic test |
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E.4 | Principal exclusion criteria |
• Any history of illness, comorbidity or lab abnormality, particularly pulmonary, cardiac or diabetes that might confound the results of the study or pose an additional risk in administering study drug to the subject.
• Use of a live attenuated intranasal spray vaccine(e.g. Flumist©) in the 3 weeks before study entry.
• Subjects who have taken antiviral medication, substrates of OATP1B1, OATP1B3, and strong inhibitors or inducers of CYP3A4, within 14 days before screening.
• Pregnant and nursing females, sexually active subjects or reproductive potential who are not willing to follow the contraception requirements.
• Subjects may not participate in an investigational study drug until the completion of this study.
• Subjects with bacterial infections requiring systemic antibacterial agents at the time of screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time from initiation of VX-787 dosing to resolution of influenza symptoms as assessed by clinical symptom scores. |
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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) |
• Safety and tolerability based on assessment of adverse events, clinical laboratory assessments, 12-lead electrocardiograms (ECGs), and vital signs
• Antiviral effect and viral kinetics in relation to:
o Duration of viral shedding in nasal secretions by qRT-PCR and viral culture
o Viral area under the concentration time curve (AUC) calculated by qRT-PCR and viral culture of nasal secretions, from baseline to Day 8
o Peak viral shedding titer by qRT-PCR and viral culture
• Clinical symptom scores
o Composite symptom score AUC
o Time to peak of composite symptom score,
o Duration and time to resolution of composite symptom score from peak
• PK parameters of VX-787, as determined by population analysis
• Viral sequence analysis to monitor for emergence of viral variants resistant to VX 787 and to oseltamivir |
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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 | Yes |
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 | 4 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Belgium |
Canada |
Estonia |
Latvia |
South Africa |
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 | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |