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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cough; Fever; Headache; Nasal Congestion; Seasonal Influenza; Sore Throat
• Intervention / Treatment: Drug: Peramivir+SOC; Drug: Placebo+SOC

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
  • Buenos Aires, Argentina, 1638
    • Hospital del Torax Dr. Antonio A. Cetrangolo
  • Caba, Argentina
  • Cordoba, Argentina
  • Mendoza, Argentina
  • Merlo, Argentina
  • Rosario, Argentina
  • Santa Fe, Argentina
  • Vicente Lopez, Argentina
• Belgium
  • Bruxelles, Belgium
  • Liege, Belgium
  • Mons, Belgium
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina
  • Tuzla, Bosnia and Herzegovina
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil
  • PR
    • Curitiba, PR, Brazil
  • RS
    • Passo Fundo, RS, Brazil
    • Porto Alegre, RS, Brazil
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
  • SP
    • Campinas, SP, Brazil
    • Santo Andre, SP, Brazil
    • Santos, SP, Brazil
    • Sao Paulo, SP, Brazil
• Bulgaria
  • Plovdiv, Bulgaria
  • Ruse, Bulgaria, 7002
    • DDPPDI - Ruse
  • Sofia, Bulgaria
  • Sofia, Bulgaria, 1606
    • Military Medical Academy - MHAT
  • Sofia, Bulgaria, 1233
    • Fifth MHAT-Sofia, AD
  • Sofia, Bulgaria, 1407
    • MHAT - Tokuda Hospital Sofia, AD
  • Stara Zagora, Bulgaria
    • MHAT - Tokuda Hospital Sofia, AD
  • Veliko Tarnovo, Bulgaria, 5000
    • MHAT 'Dr. St. Cherkezov', AD
• Canada
  • Quebec, Canada
  • British Columbia
    • Kelowna, British Columbia, Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Kingston, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Chicoutimi, Quebec, Canada
    • Sherbrooke, Quebec, Canada
• Chile
  • Concepcion, Chile
    • Hospital Clinico Regional Dr. Guillermo Grant Benavente
  • Santiago, Chile
  • Santiago, Chile, 56 2 5681332
    • Hosp. de Urgencia Asistencia Publica Dr. Alejandro del Rio
  • Temuco, Chile
• Czech Republic
  • Brno, Czech Republic, 625 00
    • Fakultni Nemocnice Brno
  • Hradec Kralove, Czech Republic
  • Praha, Czech Republic
  • Tabor, Czech Republic
  • Usti nad Labem, Czech Republic, 401 13
    • Krajska zdravotni, a.s. - Masarykova nemocnice v Ustinad La
• Germany
  • Berlin, Germany
  • Erlangen, Germany
  • Goettingen, Germany
  • Koeln, Germany
  • Mainz, Germany
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg
• Hungary
  • Debrecen, Hungary
  • Fehergyarmat, Hungary
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Korhaz
  • Szentes, Hungary, 6000
    • Principal SMO Dr. Bugyi Istvan Korhaz Szentes
  • Zalaegerszeg, Hungary
• India
  • Delhi, India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India
    • Secunderabad, Andhra Pradesh, India
  • Gujarat
    • Ahmedabad, Gujarat, India
    • Karamsad, Gujarat, India
    • Surat, Gujarat, India
    • Vadodara, Gujarat, India
  • Haryana
    • Faridabad, Haryana, India
  • Jammu & Kashmir
    • Srinagar, Jammu & Kashmir, India
  • Karnataka
    • Bangalore, Karnataka, India
    • Mangalore, Karnataka, India
  • Kerala
    • Ernakulam, Kerala, India
    • Thrissur, Kerala, India
    • Trivandrum, Kerala, India
  • Maharashtra
    • Cherthala, Maharashtra, India
    • Mumbai, Maharashtra, India
    • Nagpur, Maharashtra, India
    • Nashik, Maharashtra, India
    • Pune, Maharashtra, India
  • Punjab
    • Mohali, Punjab, India
  • Rajasthan
    • Bikaner, Rajasthan, India
    • Jaipur, Rajasthan, India, 302017
      • Fortis Escort Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India
    • Chennai, Tamil Nadu, India, 600010
      • Apollo First Med Hospitals
    • Chennai, Tamil Nadu, India, 600096
      • Life Line Multispecialty Hospital
    • Coimbatore, Tamil Nadu, India
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India
  • West Bengal
    • Kolkata, West Bengal, India
• Israel
  • Afula, Israel
  • Haifa, Israel
  • Holon, Israel
  • Jerusalem, Israel
  • Kfar Saba, Israel
  • Ramat Gan, Israel
  • Tel Aviv, Israel
• Latvia
  • Liepaja, Latvia
  • Rezekne, Latvia
  • Valmiera, Latvia
  • Ventspils, Latvia
• Lebanon
  • Beirut, Lebanon
• Peru
  • Arequipa, Peru
  • Cuzco, Peru
  • Lima, Peru
• Poland
  • Bydgoszcz, Poland
  • Lancut, Poland
  • Lodz, Poland
  • Mielec, Poland
  • Poznan, Poland
  • Pulawy, Poland
• Russian Federation
  • Engels, Russian Federation
  • Niznhy Novgorod, Russian Federation
  • Novosibirsk, Russian Federation
  • St. Petersburg, Russian Federation
  • Tomsk, Russian Federation
• Serbia
  • Belgrade, Serbia
  • Kragujevac, Serbia
  • Nis, Serbia
  • Novi Sad, Serbia
• Slovakia
  • Trnava, Slovakia
• South Africa
  • Bloemfontein, South Africa
  • Dundee, South Africa
  • Durban, South Africa
  • Krugersdorp, South Africa
  • Limpopo, South Africa
  • Port Elizabeth, South Africa
  • Pretoria, South Africa
  • Somerset West, South Africa
  • Worcester, South Africa
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa
• Ukraine
  • Chernivci, Ukraine
  • Donetsk, Ukraine
  • Kharkiv, Ukraine
  • Kyiv, Ukraine
  • Odesa, Ukraine
  • Poltava, Ukraine
  • Sumy, Ukraine
  • Vinnytsya, Ukraine
• United Kingdom
  • Leicester, United Kingdom
• United States
  • California
    • La Mesa, California, United States
    • Long Beach, California, United States
    • Modesto, California, United States
    • Oceanside, California, United States
    • Orange, California, United States
    • Orange, California, United States, 92868
      • Pulmonary Consultants PC Physicians Medical Group, Inc.
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States
    • San Diego, California, United States, 91911
      • Sharp Chula Vista Medical Center
  • Colorado
    • Denver, Colorado, United States
    • Wheat Ridge, Colorado, United States, 80033
      • Drogue Medical, Llc
  • District of Columbia
    • Washington, District of Columbia, United States
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center CAR
  • Florida
    • Ft. Lauderdale, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • West Palm Beach, Florida, United States
    • Winter Park, Florida, United States, 32790-2706
      • Florida Hospital
  • Georgia
    • Columbus, Georgia, United States
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Savannah, Georgia, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Illinois
    • Moline, Illinois, United States, 61265
      • Medical Arts Associates, Ltd.
    • Springfield, Illinois, United States
  • Indiana
    • South Bend, Indiana, United States
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Lung Clinic
  • Louisiana
    • Natchitoches, Louisiana, United States
    • New Orleans, Louisiana, United States
  • Maryland
    • Annapolis, Maryland, United States
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States
    • Detroit, Michigan, United States, 48201
      • Wayne State University - Hutzel Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University, Department of Emergency Medicine
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St. Louis, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • New Brunswick, New Jersey, United States
  • New York
    • Bronx, New York, United States
    • Manhasset, New York, United States
    • New York, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill AIDS Clinical Trials Unit
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis, Inc.
    • Dayton, Ohio, United States
    • Kettering, Ohio, United States
    • Lima, Ohio, United States, 45801
      • Regional Infection Diseases Infusion Center Inc.
    • Toledo, Ohio, United States
    • Toledo, Ohio, United States, 43614
      • Medical College of Ohio
    • Toledo, Ohio, United States, 43608
      • ID Clinical Research, LTD
  • Pennsylvania
    • Allentown, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
  • Rhode Island
    • East Providence, Rhode Island, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • South Dakota
    • Sioux Falls, South Dakota, United States
  • Texas
    • San Antonio, Texas, United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Roanoke, Virginia, United States, 24014
      • Carilion Infectious Disease
    • Salem, Virginia, United States, 24153
      • VA Medical Center - Salem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peramivir+SOC; 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.	Drug: Peramivir+SOC; 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 Comparator: Placebo+SOC; Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Drug: Placebo+SOC; Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Resolution (Kaplan-Meier Estimate)	Time to clinical resolution was defined as the time in hours from initiation of study treatment until normalization of at least 4 of the 5 signs within the respective normalization criteria, maintained for at least 24-hours. Time to clinical resolution was summarized by treatment group using the method of Kaplan-Meier. For subjects who did not experience clinical resolution, values were censored at the date of their last non-missing assessment of clinical resolution during the study (whether this assessment occurred as an inpatient or as an outpatient).	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change (Reduction) in Influenza Virus Titer	The reduction in viral shedding was assessed as the change from baseline in log10 tissue culture infective dose50 (TCID50/mL) and RT-PCR and was summarized for each treatment group and study visit.	Baseline and 24, 48, 108 hours
Time to Alleviation of Clinical Symptoms of Influenza	Time to alleviation of clinical symptoms of influenza was measured as the time from the first dose of study drug through the time period in which all 7 symptoms of influenza (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) were absent or rated as no greater than mild for at least 24 hours. Time to alleviation of symptoms was estimated using the method of Kaplan-Meier. Subjects who did not have resolution of any individual clinical sign were censored at the time of their last non-missing assessment of that sign.	10 days
Time to Resolution of Fever (Kaplan-Meier Estimate)	Time to resolution of fever was measured as the time from initiation of study treatment until resolution of fever, maintained for at least 24 hours; temperature measurements taken less than 4 hours after antipyretic use were treated as missing values.	10 days
Time to Resumption of Usual Activities	Time to resumption of usual activities was determined from the visual analog scale (scale ranged from 0 to 10 where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully). Time to resumption of usual activities was summarized by treatment group using the method of Kaplan-Meier.	10 days
Number of Subjects With ICU Admission	The number of subjects requiring ICU admission post-randomization was summarized by treatment group.	10 days
Duration of All ICU Admissions (Kaplan-Meier Estimate)	Duration of postbaseline ICU admission was defined as the total number of days in the ICU for those subjects who had a post-baseline admission to the ICU. Only days starting after the initial postbaseline admission were included. If a subject's stay in the ICU was ongoing, the duration was censored at the last study visit. Subjects who did not have a postbaseline admission had a duration of 0.	10 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Hospital Discharge	Time to hospital discharge, defined as the number of days from initiation of study treatment until the subject was discharged from the hospital, was summarized by treatment group using the method of Kaplan-Meier. Subjects who were not discharged from the hospital were censored at their last study visit.	10 days
Incidence of Influenza-Related Complications	Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis, and pneumonia as reported on the influenza-related complications CRF.	10 days
Number of Subjects Requiring More Than 5 Days of Study Drug	Subjects who had not met the protocol-defined criteria of clinical resolution on Day 5 or who had detectable virus by RT-PCR from a sample collected on Study Day 4 after dosing continued their assigned treatment for a further 5 days.	10 days
Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate)	Survival was calculated as the number of days from initiation of study drug until death or last contact. Estimates and 95% confidence intervals were calculated using the method of Kaplan-Meier and presented by treatment group.	28 days
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM)	Initial viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.	Initial (baseline or post-baseline) and up to 10 days
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial	Viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented as fold change from initial sensitivity by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.	Initial (baseline or post-baseline) and up to 10 days

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Collaborators: Department of Health and Human Services

Publications and helpful links

General Publications

• de Jong MD, Ison MG, Monto AS, Metev H, Clark C, O'Neil B, Elder J, McCullough A, Collis P, Sheridan WP. Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. Clin Infect Dis. 2014 Dec 15;59(12):e172-85. doi: 10.1093/cid/ciu632. Epub 2014 Aug 12.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: August 12, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): February 12, 2015
• Last Update Submitted That Met QC Criteria: January 28, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Hospitalized; Flu; Antiviral
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pain; Neurologic Manifestations; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Orthomyxoviridae Infections; Influenza, Human; Headache; Pharyngitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Peramivir
• Other Study ID Numbers: BCX1812-301