E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022000 |
E.1.2 | Term | Influenza |
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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 treatment with peramivir plus standard of care (SOC) compared to placebo plus SOC on time to clinical resolution in adults and adolescents who are hospitalized with acute influenza. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the safety and tolerability of peramivir plus SOC compared to placebo plus SOC in adults and adolescents who are hospitalized with acute influenza, hereafter shortened to "peramivir vs. placebo".
Evaluate changes in viral shedding associated with treatment with "peramivir vs. placebo".
Evaluate the effect on time to alleviation of symptoms, time to resumption of usual daily activities, time to hospital discharge, incidence of influenza-related complications and mortality associated with treatment with "peramivir vs. placebo".
Evaluate changes in viral phenotype and genotype between baseline and post-treatment samples associated with treatment with "peramivir vs. placebo".
To describe the pharmacokinetics of peramivir in adults and adolescents who are hospitalized with acute infection.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥12 years of age, male or female.
2. Able to provide informed consent, or for whom consent may be provided by guardian, unless informed consent provided by a guardian or a legally authorized representative is not consistent with applicable local or ethical concerns, procedures, directives and/or guidelines.
3. Subject must have at least one of the following clinical presentations: a. Oral temperature > 38.0 °C (>100.4 °F), ≥38.6°C (101.4 °F) tympanic or rectal OR b. Oxygen saturation <92%, OR c. Two out of the following three vital signs: • Respiration rate >24/minute • Heart rate >100/minute • Systolic BP <90 mmHg
4. Presence of at least one respiratory symptom (cough, sore throat, or nasal congestion) of any severity (mild, moderate, or severe).
5. Presence of at least one constitutional symptom (headache, myalgia, feverishness, or fatigue) of any severity (mild, moderate, or severe).
6. Onset of illness no more than 72 hours before presentation. Note: Time of onset of illness is defined as either (1) the time when the temperature was first measured as elevated, OR (2) the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
7. Either: Severity of illness that, in the Investigator’s judgment, justifies hospitalization of the subject for supportive care. OR Presence of one or more of the following factors: •Age ≥60 years. •Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy. •Current history of congestive heart failure or angina. •Presence of diabetes mellitus, clinically stable or unstable. •Transcutaneous oxygen saturation <94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value (an investigative site at altitude >2000 ft above sea level will utilize different criteria for oxygen saturation). •History of chronic renal impairment not requiring dialysis. •Serum creatinine > 2.0 mg/dL.
8. Diagnosis of Influenza by satisfying one of the following: a. Clinical Influenza with Positive Diagnostic Test. Subjects who have a positive rapid antigen test (RAT) for influenza A and/or influenza B (using a Sponsor-approved test kit), or positive test (using other methodology) for influenza A and/or B virus antigen or RNA performed in a clinical laboratory at the screening/enrollment evaluation are eligible for enrollment. OR b. Clinical Influenza with Negative Rapid Antigen Test (RAT). Subjects with a negative RAT or other clinical laboratory test may be enrolled once the site has been approved by the Sponsor to enroll such subjects, based on documentation of an outbreak of influenza in the community. An influenza outbreak may be documented in the catchment area of the hospital via one of the following methods: 1) local confirmation of influenza A or B infection in the current influenza season by a) the institution’s local laboratory, or b) the local public health system, or c) the national public health system, or d) a laboratory of a recognized multinational influenza surveillance scheme such as the European Influenza Surveillance Scheme (EISS); 2) prior enrollment of a RAT positive subject into this study at the same institution in the current influenza season.
9. Females must fulfill one of the following conditions: •Subject is surgically sterile or clinically post-menopausal. •Subject has been sexually abstinent 4 weeks prior to date of screening evaluation and is willing to remain abstinent through 4 weeks after study-drug administration. •Subject has been using oral contraceptives or other form of hormonal birth control including hormonal vaginal rings or transdermal patches for 3 months prior to the study, and use will continue through 4 weeks after study-drug administration. •Subject has been using an intra-uterine device, or adequate double-barrier method such as condom or diaphragm with spermicidal gel or foam as birth control 4 weeks prior to date of Screening evaluation, and use will continue through 4 weeks after study drug administration. •Subject is the spouse or monogamous partner of a male who has undergone a vasectomy.
10. Males will ensure that their female partners of childbearing potential will utilize approved contraceptive methods to avoid pregnancy.
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E.4 | Principal exclusion criteria |
1. Subjects who have developed clinical manifestations of influenza after having been hospitalized for greater than 24 hours for a condition other than confirmed or suspected influenza.
2. Treatment with any dose(s) of rimantadine, amantadine, ribavirin, zanamivir, or oseltamivir in the previous 7 days.
3. Blood platelet count of < 20 x 1,000,000,000/L.
4. Serum bilirubin > 6 mg/dL at time of screening evaluation.
5. Serum ALT or AST > 5 times the upper limit of normal at time of screening evaluation.
6. Congestive heart failure of NYHA Class III or Class IV functional status.
7. Requirement for vasopressor support to maintain satisfactory hemodynamic status at time of screening evaluation.
8. Serum creatinine > 5.0 mg/dL at time of screening evaluation.
9. Subjects who require peritoneal dialysis or hemofiltration.
10. Altered neurologic status as defined by a Glasgow Coma Score of ≤ 9, unless medically induced.
11. Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or lactating.
12. Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy.
13. Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months.
14. HIV infection with a known CD4 count < 200 cells/mm3 unless on a stable highly active antiretroviral regimen (HAART) for at least 6 months.
15. Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). Subjects with chronic osteomyelitis are not excluded.
16. Presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.
17. Previous treatment with intravenous or intramuscular peramivir.
18. Participation as a subject in any study of an experimental treatment for any condition within the 30 days prior to the time of the screening evaluation.
19. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to clinical resolution as defined as the time in hours from initiation of study treatment until resolution of at least 4 of the 5 signs described below within the respective resolution criteria shown, maintained for at least 24 hours:
Note: It is mandatory that both temperature and oxygen saturation meet Resolution Criteria in order for the clinical resolution endpoint to be met.
Sign of Clinical Resolution Resolution Criteria
Temperature ≤37.2 °C (≤99 °F) oral ≤37.8°C (≤100°F) rectal or tympanic
Oxygen saturation ≥92%
Respiration rate ≤24/minute
Heart rate ≤100/minute
Systolic BP ≥90 mm Hg
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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 | No |
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) | 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 | 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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
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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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End of Trial will be the last patient, last visit 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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |