E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of influenza in immunocompromised patients. |
Trattamento dell`influenza in pazienti immunocompromessi. |
|
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. |
Valutare quale sia la dose migliore per trattare l`influenza in pazienti con un sistema immunitario (di protezione) indebolito. |
|
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 | 14.1 |
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 |
Valutare prospetticamente la sicurezza e la tollerabilità di oseltamivir per il trattamento dell`influenza in pazienti immunocompromessi e qualificare gli effetti di oseltamivir in pazienti immunocompromessi per quel che concerne lo sviluppo di virus resistenti all`influenza. |
|
E.2.2 | Secondary objectives of the trial |
• The time to resolution of influenza symptoms • The clinical course of influenza (fever, symptoms, secondary illnesses as evidenced by otitis media, bronchitis, pneumonia, or sinusitis) • The virologic course of influenza (proportion shedding and viral loads at different time points) |
•Tempo impiegato per ottenere la risoluzione dei sintomi influenzali•Decorso clinico dell`influenza (febbre,sintomi,patologie secondarie evidenziate da otite media,bronchite,polmonite o sinusite)•Decorso virologico dell`influenza (eliminazione in proporzione e cariche virali in diversi punti temporali). |
|
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 in the 96 hours prior to first dose; • Immunocompromised subject defined as one who meets any of the following: o Primary immunodeficiency at risk for viral infections (representative examples in Appendix 6) OR o Secondary immunodeficiency ô SOT with ongoing immunosuppression OR ô Allogenic HSCT with ongoing immunosuppression OR ô HIV with CD4 count < 200/mm3 OR ô Hematologic malignancies (representative examples in Appendix 7) OR ô 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 (representative examples in Appendix 8) • Symptoms suggestive of influenza like illness including, but not limited to fever, cough, or coryza; • In patients with history or clinical presentation at randomization suggestive of renal failure; a CrCl > 60 ml/min/1.73M2; • Less than or equal to 96 hours between onset of influenza like illness and first dose of study drug; • Parent/guardian willing and able to comply with study requirements and give consent, (country specific age cut off) • Patient able to comply with study requirements and willing to give assent, as appropriate (country specific age cut off); • For adult patients, willing and able to comprehend and give written informed consent; • Patients, in the reproductive age group, must agree to utilize an effective method of contraception throughout the study period and for females for one reproductive cycle following cessation of study therapy; • Females of childbearing potential must have a negative urine pregnancy test prior to start of study medication |
- |
|
E.4 | Principal exclusion criteria |
• SOT within 6 months of the time of randomization; • Have in the investigator`s opinion experienced acute rejection in the 4 weeks prior to randomization; • HSCT patients with no evidence of engraftment (engraftment is defined as the point at which a patient can maintain a sustained absolute neutrophil count (ANC) of > 500/mm3 and sustained platelet count of `¥ 20,000/mm3, lasting `¥ 3 consecutive days without transfusions). • HSCT subjects not discharged from hospital after their initial hospitalization for transplantation. • Have clinical evidence for hepatic decompensation at the time of randomization (clinical icterus, ascites, hepatic encephalopathy, coagulopathy). • Have cirrhosis of the liver at the time of randomization. • Patients currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis or hemofiltration. • Have evidence of active or uncontrolled opportunistic infections (bacterial, fungal, or viral-including cytomegalovirus [CMV] or polyoma virus [BKV]) at the time of randomization. Patients with HCV or HBV are not excluded. • Patients with co-morbid conditions which are uncontrolled. Uncontrolled is defined as disease requiring change of therapy or hospitalization in the 4 weeks preceding randomization. Change of therapy is defined as dose increase or change of medication prior to onset of present influenza like illness. • Patients with gastrointestinal disorders which might interfere with their ability to absorb oral medication. • Allergy to the test medication. • Patients with hereditary fructose intolerance (for subjects who will be taking the liquid formulation). • Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization. • Antiviral treatment (example: amantadine, rimantadine, oseltamivir, laninamivir, peramivir, zanamivir and ribavirin) for influenza in the 2 weeks prior to randomization. • Patients taking probenecid medication. • Patients who are pregnant or breast-feeding. • Participation in a clinical trial or expanded access trial with an investigational drug in the 4 weeks prior to randomization or concomitantly with this study. |
- |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are safety and development of resistance. |
Gli end-points primari sono sicurezza e sviluppo di resistenza. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time points up to day 40. |
Tempi di rilevazione fino al giorno 40. |
|
E.5.2 | Secondary end point(s) |
- The time to alleviation of all clinical influenza symptoms - Shedding virus at day 1, 2, 6, 8, 11, 15 and 40 - Viral load at day 1, 2, 6, 8, 11, 15 and 40 - The time until resolution of fever - Development of secondary illnesses at any time during the study - Development of secondary illnesses at any time during the study that are treated with antibiotics - Initiation of treatment with antibiotics after randomization |
- |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time points up to day 40. |
Tempi di rilevazione fino al giorno 40. |
|
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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Development of resistance |
Sviluppo di resistenza |
|
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) | 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.8.2.4 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
Canada |
Israel |
Switzerland |
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. A rapid diagnostic test for influenza will be performed at the end of the 10 days of treatment. |
Lo studio prevede 10 gg di trattamento con visite di follow-up 5 e 30 gg dopo l`ultima somministrazione (vedere schedule of assessment). Un rapido test diagnostico sara' effettuato dopo i 10 gg di trattamento. |
|
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 |