A Phase 3, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Peramivir Administered Intravenously in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Serious Influenza
The influenza virus causes an acute viral disease of the respiratory tract. Unlike the common cold and some other respiratory infections, seasonal flu can cause severe illness, resulting in life-threatening complications. According to the CDC, an estimated 5% to 20% of the American population suffers from influenza annually, and there are approximately 3,000 to 49,000 flu-related deaths per year in the U.S. Most at risk are young children, the elderly and people with seriously compromised immune systems.
Peramivir is a potent, intravenously administered investigational antiviral agent that rapidly delivers high plasma concentrations to the sites of infection. Discovered by BioCryst, peramivir inhibits the interactions of influenza neuraminidase, an enzyme that is critical to the spread of influenza within the host. Peramivir is an inhibitor of influenza A and B viruses, including strains of influenza viruses that may be resistant to available neuraminidase inhibitors. In January 2006, BioCryst received United States Food and Drug Administration (FDA) Fast Track designation for peramivir. The availability of an intravenous (i.v.) neuraminidase inhibitor may be important in treating patients hospitalized with severe and potentially life-threatening influenza by ensuring that the appropriate dose is administered, which may be a concern with currently available oral or inhaled anti-influenza agents.
- Age ≥12 years of age, male or female.
- 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.
Subject must have at least one of the following clinical presentations at Screening:
- Oral temperature ≥ 38.0 °C (≥100.4 °F), ≥38.6°C (≥101.4 °F) tympanic or rectal OR
- Oxygen saturation less than 92%, OR
- Two out of the following three vital signs:
- Respiration rate >24/minute
- Heart rate >100/minute
- Systolic BP less than 90 mmHg
- Presence of at least one respiratory symptom (cough, sore throat, or nasal congestion) of any severity (mild, moderate, or severe).
- Presence of at least one constitutional symptom (headache, myalgia, feverishness, or fatigue) of any severity (mild, moderate, or severe).
- Onset of illness no more than 72 hours before presentation. Note: Time of onset of illness is defined as the earlier of 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.
- Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care.
- 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 less than 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 peritoneal dialysis. Serum creatinine > 2.0 mg/dL or > 200 μmol/L.
Diagnosis of Influenza by satisfying one of the following:
- 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.
- Clinical Influenza with Negative Rapid Antigen Test (RAT). Subjects with a negative RAT 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 Network (EISN); 2) prior enrollment of a RAT positive subject into this study at the same institution in the current influenza season.
- Subjects who have been hospitalized for greater than 24 hours (not including time spent in the Emergency Department).
- Treatment with any dose(s) of rimantadine, amantadine, ribavirin, zanamivir, or oseltamivir in the previous 7 days.
- Blood platelet count of less than 20 x 109/L at the time of the screening evaluation.
- Serum bilirubin > 6 mg/dL or > 105 μmol/L at time of screening evaluation.
- Serum ALT or AST > 5 times the upper limit of normal at time of screening evaluation.
- Congestive heart failure of NYHA Class III or Class IV functional status.
- Serum creatinine > 5.0 mg/dL or > 500 μmol/L at time of screening evaluation.
- Subjects who require peritoneal dialysis.
- Altered neurologic status as defined by a Glasgow Coma Score of ≤ 9, unless medically induced.
- Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or breastfeeding.
- Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. Subjects who have completed treatment 30 days prior to enrollment are not excluded. Hormone treatment for cancer is also not excluded.
- Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months.
- HIV infection with a known CD4 count less than 200 cells/mm3 unless on a stable highly active antiretroviral therapy (HAART) for at least 6 months.
- Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). Subjects with chronic osteomyelitis or Hepatitis B or C not requiring treatment are not excluded.
- 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.
- Previous treatment with intravenous or intramuscular peramivir.
- 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.
- Subjects diagnosed with Cystic Fibrosis.
- Subjects with confirmed clinical evidence of acute non-influenzal infection at the time of screening evaluation.
- Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
Charles Schleupner, M.D.
Karen G. Baker
Clinical Research Nurse