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 transplant recipients. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022000 |
E.1.2 | Term | Influenza |
|
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 efficacy of oseltamivir for the treatment of influenza in transplant recipients as measured by the time to resolution of influenza symptoms |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effects of conventional and high dose oseltamivir in transplant recipients on: • 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) • Patient safety and tolerability • The development of resistant influenza virus |
|
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 positive for influenza in the 24 hours prior to first dose • Immunocompromised subject defined as documented: - SOT (liver, kidney or both) recipient OR - Allogenic HSCT • Receiving ongoing immunosuppression, OR, in the investigator’s opinion, not immune reconstituted • Symptoms suggestive of influenza like illness including, but not limited to fever, cough, or coryza • Less or equal 48 hours between onset of influenza like illness and first dose of study drug • Acceptable renal function defined as: - Most recent creatinine clearance in the 6 months prior to randomization is > 30 ml/min in adults and > 30 ml/min /1.73M2 (metre squared) in children. Creatinine clearance estimated from serum creatinine measured when subject is not receiving any renal replacement therapy OR - For patients who have not had a creatinine clearance assessment in the 6 months prior to randomization, baseline creatinine clearance > 10 ml/min in adults and > 10 ml/min /1.73M2 (metre squared) in children OR - For patients whose most recent creatinine clearance in the 6 months prior to randomization is < 30 ml/min in adults and < 30 ml/min /1.73M2 (metre squared) in children, baseline creatinine clearance > 10 ml/min in adults and > 10 ml/min /1.73M2 (metre squared) in children • 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 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 • Solid Organ Transplant other than liver, kidney or liver and kidney • 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 evidence of veno-occlusive disease, acute or chronic extensive graft versus host disease at the time of randomization • 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 • Currently or in the six months prior to randomization using T cell depleting antibodies (example: antithymocyte globulin, antilymphocyte globulin) for management of transplant • Have other co-morbid conditions that could affect patient survival or graft function including, but not limited to, a post-transplant lymphoproliferative disease (PTLD), autoimmune disease including inflammatory bowel disease and psoriasis, untreated thyroid disease, and significant active infection • 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 known HIV infection • Patients who are being evaluated or treated for an active malignancy (other than the malignancy for which the SOT or HSCT may have been performed) at the time of randomization • Patients with uncontrolled vascular, neurologic or pulmonary disease. 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 severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy • Allergy to the test medication • Patients with hereditary fructose intolerance (for subjects who will be taking the liquid formulation) • Influenza vaccination in the 2 weeks prior to randomization • Antiviral treatment (example: amantadine, rimantadine, 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 endpoint in this study is the time to resolution of all influenza symptoms as recorded in the patient diary. |
|
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 | No |
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 | 140 |
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 | Information not present in EudraCT |
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 |
|
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
| |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |