A Study to Evaluate the Efficacy and Safety of IV Peramivir in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Influenza
Condition: Cough; Sore Throat; Nasal Congestion; Headache; Fever; Seasonal Influenza
MeSH terms: Influenza, Human; Pharyngitis; Headache
Intervention: Peramivir+SOC; Placebo+SOC
Intervention description: Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.; Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Intervention MeSH terms: Peramivir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 405.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Influenza; Hospitalized; Antiviral; Flu

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               1. Oral temperature ≥ 38.0 °C (≥100.4 °F), ≥38.6°C (≥101.4 °F) tympanic or rectal OR

               2. Oxygen saturation <92%, OR

               3. Two out of the following three vital signs:

        Respiration rate >24/minute, Heart rate >100/minute, Systolic BP <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.

          -  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 peritoneal dialysis. Serum creatinine >
        2.0 mg/dL or > 177 μmol/L.

          -  Diagnosis of Influenza by satisfying one of the following:

               1. 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

               2. 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.

                  Exclusion Criteria:

          -  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 < 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 < 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.