E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To investigate the optimal therapy for influenza in immunocompromised patients. |
|
E.1.1.1 | Medical condition in easily understood language |
To explore which dose is best to treat the flu in patients with a weakened immune (protective) system |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022000 |
E.1.2 | Term | Influenza |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 prospectively the safety and tolerability of oseltamivir for the treatment of influenza in immunocompromized patients and characterize the effects of oseltamivir in immunocompromized patients on the development of resistant influenza virus |
|
E.2.2 | Secondary objectives of the trial |
- Pharmacokinetics of oseltamivir carboxylate (e.g., clearance, volume of distribution) in immunocompromised patients with confirmed influenza infection
- Time to resolution of influenza symptoms
- Virologic course of influenza
- Clinical course of influenza
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age greater than or equal to 1 year
• Rapid diagnostic test, PCR, or viral culture positive for influenza
• Immunocompromised subject defined as one who meets any of the following:
- Primary immunodeficiency at risk for viral infections OR
- Secondary immunodeficiency
- SOT with ongoing immunosuppression OR
- Allogenic HSCT with ongoing immunosuppression
OR
- HIV with CD4 count < 500/mm3 and, in the investigator's opinion, considered immunocompromised OR
- Hematologic malignancies OR
- Systemic (e.g. enteric, sc, im or iv)
immunosuppressive therapy, irrespective of medical indication, started at least 12 weeks prior to, and ongoing at the time of first dose of study drug
• Symptoms suggestive of influenza like illness including, but not limited to fever, cough, or coryza
• Use of an effective contraceptive, as specified by protocol; women of
childbearing potential cannot be pregnant or breastfeeding. |
|
E.4 | Principal exclusion criteria |
• Influenza vaccination with live attenuated vaccine in the 2 weeks prior
to randomization
• Antiviral treatment for influenza in 2 weeks prior to randomization
• Severe hepatic impairment
• Any current renal replacement therapy
• Any gastrointestinal disorders which may intefere with the absorption
of Tamiflu
• Participation in a study with an investigational drug from 4 weeks prior
to study start until study end |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are safety and development of resistance |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Time to alleviation of all clinical influenza symptoms
2. Proportion of viral shedding
3. Viral load
4. Development of secondary illnesses
5. Pharmacokinetics: Area under the concentration-time curve (AUC)7. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.- 4.: Time points up to day 40
5.: Samples for PK analysis will be collected at Day 6 |
|
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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Development of resistance |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 50 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Czech Republic |
Estonia |
France |
Germany |
Hungary |
Israel |
Italy |
Latvia |
Lithuania |
Poland |
Romania |
South Africa |
Spain |
Switzerland |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The study comprises 10 days of treatment with follow up visits approximately 5 and 30 days later as shown in the schedule of assessments. Study medication will be administered twice daily over 10 days for a total of 20 doses. A rapid diagnostic test for influenza will be performed at the end of the 10 days of treatment. Subjects still having influenza based on the rapid diagnostic test will be treated per the local standard of care by the principal investigator. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
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 |