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
Sponsor
BioCryst Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT00958776
Collaborator
Department of Health and Human Services (U.S. Fed)
405
196
2
47
2.1
0
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
405 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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 Start Date
:
Nov 1, 2009
Actual Primary Completion Date
:
Nov 1, 2012
Actual Study Completion Date
:
Oct 1, 2013
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Time to Clinical Resolution (Kaplan-Meier Estimate) [10 days]
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).
Secondary Outcome Measures
- Change (Reduction) in Influenza Virus Titer [Baseline and 24, 48, 108 hours]
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.
- Time to Alleviation of Clinical Symptoms of Influenza [10 days]
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.
- Time to Resolution of Fever (Kaplan-Meier Estimate) [10 days]
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.
- Time to Resumption of Usual Activities [10 days]
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.
- Number of Subjects With ICU Admission [10 days]
The number of subjects requiring ICU admission post-randomization was summarized by treatment group.
- Duration of All ICU Admissions (Kaplan-Meier Estimate) [10 days]
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.
Other Outcome Measures
- Time to Hospital Discharge [10 days]
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.
- Incidence of Influenza-Related Complications [10 days]
Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis, and pneumonia as reported on the influenza-related complications CRF.
- Number of Subjects Requiring More Than 5 Days of Study Drug [10 days]
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.
- Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate) [28 days]
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.
- Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) [Initial (baseline or post-baseline) and up to 10 days]
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.
- Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial [Initial (baseline or post-baseline) and up to 10 days]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:
-
Oral temperature ≥ 38.0 °C (≥100.4 °F), ≥38.6°C (≥101.4 °F) tympanic or rectal OR
-
Oxygen saturation <92%, OR
-
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:
- 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
- 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);
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | La Mesa | California | United States | ||
| 2 | Long Beach | California | United States | ||
| 3 | Modesto | California | United States | ||
| 4 | Oceanside | California | United States | ||
| 5 | Pulmonary Consultants PC Physicians Medical Group, Inc. | Orange | California | United States | 92868 |
| 6 | Orange | California | United States | ||
| 7 | UC Davis Medical Center | Sacramento | California | United States | 95817 |
| 8 | Sharp Chula Vista Medical Center | San Diego | California | United States | 91911 |
| 9 | San Diego | California | United States | ||
| 10 | Denver | Colorado | United States | ||
| 11 | Drogue Medical, LLC | Wheat Ridge | Colorado | United States | 80033 |
| 12 | Washington Hospital Center CAR | Washington | District of Columbia | United States | 20010 |
| 13 | Washington | District of Columbia | United States | ||
| 14 | Ft. Lauderdale | Florida | United States | ||
| 15 | Miami | Florida | United States | ||
| 16 | Orlando | Florida | United States | ||
| 17 | West Palm Beach | Florida | United States | ||
| 18 | Florida Hospital | Winter Park | Florida | United States | 32790-2706 |
| 19 | Columbus | Georgia | United States | ||
| 20 | DeKalb Medical Center | Decatur | Georgia | United States | 30033 |
| 21 | Savannah | Georgia | United States | ||
| 22 | Honolulu | Hawaii | United States | ||
| 23 | Medical Arts Associates, Ltd. | Moline | Illinois | United States | 61265 |
| 24 | Springfield | Illinois | United States | ||
| 25 | South Bend | Indiana | United States | ||
| 26 | Kentucky Lung Clinic | Hazard | Kentucky | United States | 41701 |
| 27 | Natchitoches | Louisiana | United States | ||
| 28 | New Orleans | Louisiana | United States | ||
| 29 | Annapolis | Maryland | United States | ||
| 30 | Baltimore | Maryland | United States | ||
| 31 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 32 | Wayne State University - Hutzel Hospital | Detroit | Michigan | United States | 48201 |
| 33 | Wayne State University, Department of Emergency Medicine | Detroit | Michigan | United States | 48201 |
| 34 | Detroit | Michigan | United States | ||
| 35 | William Beaumont Hospital | Royal Oak | Michigan | United States | 48073 |
| 36 | William Beaumont Hospital | Troy | Michigan | United States | 48085 |
| 37 | Washington University School of Medicine | St. Louis | Missouri | United States | 63110 |
| 38 | St. Louis | Missouri | United States | ||
| 39 | Las Vegas | Nevada | United States | ||
| 40 | New Brunswick | New Jersey | United States | ||
| 41 | Bronx | New York | United States | ||
| 42 | Manhasset | New York | United States | ||
| 43 | New York | New York | United States | ||
| 44 | University of North Carolina at Chapel Hill AIDS Clinical Trials Unit | Chapel Hill | North Carolina | United States | 27599 |
| 45 | Remington-Davis, Inc. | Columbus | Ohio | United States | 43215 |
| 46 | Dayton | Ohio | United States | ||
| 47 | Kettering | Ohio | United States | ||
| 48 | Regional Infection Diseases Infusion Center Inc. | Lima | Ohio | United States | 45801 |
| 49 | ID Clinical Research, LTD | Toledo | Ohio | United States | 43608 |
| 50 | Medical College Of Ohio | Toledo | Ohio | United States | 43614 |
| 51 | Toledo | Ohio | United States | ||
| 52 | Allentown | Pennsylvania | United States | ||
| 53 | Philadelphia | Pennsylvania | United States | ||
| 54 | East Providence | Rhode Island | United States | ||
| 55 | Charleston | South Carolina | United States | ||
| 56 | Sioux Falls | South Dakota | United States | ||
| 57 | San Antonio | Texas | United States | ||
| 58 | University of Virginia Health System | Charlottesville | Virginia | United States | 22908 |
| 59 | Carilion Infectious Disease | Roanoke | Virginia | United States | 24014 |
| 60 | VA Medical Center - Salem | Salem | Virginia | United States | 24153 |
| 61 | Hospital del Torax Dr. Antonio A. Cetrangolo | Buenos Aires | Argentina | 1638 | |
| 62 | Buenos Aires | Argentina | |||
| 63 | Caba | Argentina | |||
| 64 | Cordoba | Argentina | |||
| 65 | Mendoza | Argentina | |||
| 66 | Merlo | Argentina | |||
| 67 | Rosario | Argentina | |||
| 68 | Santa Fe | Argentina | |||
| 69 | Vicente Lopez | Argentina | |||
| 70 | Bruxelles | Belgium | |||
| 71 | Liege | Belgium | |||
| 72 | Mons | Belgium | |||
| 73 | Sarajevo | Bosnia and Herzegovina | |||
| 74 | Tuzla | Bosnia and Herzegovina | |||
| 75 | Belo Horizonte | MG | Brazil | ||
| 76 | Curitiba | PR | Brazil | ||
| 77 | Passo Fundo | RS | Brazil | ||
| 78 | Hospital de Clinicas de Porto Alegre | Porto Alegre | RS | Brazil | 90035-903 |
| 79 | Porto Alegre | RS | Brazil | ||
| 80 | Campinas | SP | Brazil | ||
| 81 | Santo Andre | SP | Brazil | ||
| 82 | Santos | SP | Brazil | ||
| 83 | Sao Paulo | SP | Brazil | ||
| 84 | Plovdiv | Bulgaria | |||
| 85 | DDPPDI - Ruse | Ruse | Bulgaria | 7002 | |
| 86 | Fifth MHAT-Sofia, AD | Sofia | Bulgaria | 1233 | |
| 87 | MHAT - Tokuda Hospital Sofia, AD | Sofia | Bulgaria | 1407 | |
| 88 | Military Medical Academy - MHAT | Sofia | Bulgaria | 1606 | |
| 89 | Sofia | Bulgaria | |||
| 90 | MHAT - Tokuda Hospital Sofia, AD | Stara Zagora | Bulgaria | ||
| 91 | MHAT 'Dr. St. Cherkezov', AD | Veliko Tarnovo | Bulgaria | 5000 | |
| 92 | Kelowna | British Columbia | Canada | ||
| 93 | St. Joseph's Healthcare Hamilton | Hamilton | Ontario | Canada | L8N 4A6 |
| 94 | Kingston | Ontario | Canada | ||
| 95 | Toronto | Ontario | Canada | ||
| 96 | Chicoutimi | Quebec | Canada | ||
| 97 | Sherbrooke | Quebec | Canada | ||
| 98 | Quebec | Canada | |||
| 99 | Hospital Clinico Regional Dr. Guillermo Grant Benavente | Concepcion | Chile | ||
| 100 | Hosp. de Urgencia Asistencia Publica Dr. Alejandro del Rio | Santiago | Chile | 56 2 5681332 | |
| 101 | Santiago | Chile | |||
| 102 | Temuco | Chile | |||
| 103 | Fakultni nemocnice Brno | Brno | Czech Republic | 625 00 | |
| 104 | Hradec Kralove | Czech Republic | |||
| 105 | Praha | Czech Republic | |||
| 106 | Tabor | Czech Republic | |||
| 107 | Krajska zdravotni, a.s. - Masarykova nemocnice v Ustinad La | Usti nad Labem | Czech Republic | 401 13 | |
| 108 | Berlin | Germany | |||
| 109 | Erlangen | Germany | |||
| 110 | Goettingen | Germany | |||
| 111 | Koeln | Germany | |||
| 112 | Mainz | Germany | |||
| 113 | Universitaetsklinikum Regensburg | Regensburg | Germany | 93053 | |
| 114 | Debrecen | Hungary | |||
| 115 | Fehergyarmat | Hungary | |||
| 116 | Fejer Megyei Szent Gyorgy Korhaz | Szekesfehervar | Hungary | 8000 | |
| 117 | Principal SMO Dr. Bugyi Istvan Korhaz Szentes | Szentes | Hungary | 6000 | |
| 118 | Zalaegerszeg | Hungary | |||
| 119 | Hyderabad | Andhra Pradesh | India | ||
| 120 | Secunderabad | Andhra Pradesh | India | ||
| 121 | Ahmedabad | Gujarat | India | ||
| 122 | Karamsad | Gujarat | India | ||
| 123 | Surat | Gujarat | India | ||
| 124 | Vadodara | Gujarat | India | ||
| 125 | Faridabad | Haryana | India | ||
| 126 | Srinagar | Jammu & Kashmir | India | ||
| 127 | Bangalore | Karnataka | India | ||
| 128 | Mangalore | Karnataka | India | ||
| 129 | Ernakulam | Kerala | India | ||
| 130 | Thrissur | Kerala | India | ||
| 131 | Trivandrum | Kerala | India | ||
| 132 | Cherthala | Maharashtra | India | ||
| 133 | Mumbai | Maharashtra | India | ||
| 134 | Nagpur | Maharashtra | India | ||
| 135 | Nashik | Maharashtra | India | ||
| 136 | Pune | Maharashtra | India | ||
| 137 | Mohali | Punjab | India | ||
| 138 | Bikaner | Rajasthan | India | ||
| 139 | Fortis Escort Hospital | Jaipur | Rajasthan | India | 302017 |
| 140 | Apollo First Med Hospitals | Chennai | Tamil Nadu | India | 600010 |
| 141 | Life Line Multispecialty Hospital | Chennai | Tamil Nadu | India | 600096 |
| 142 | Chennai | Tamil Nadu | India | ||
| 143 | Coimbatore | Tamil Nadu | India | ||
| 144 | Lucknow | Uttar Pradesh | India | ||
| 145 | Kolkata | West Bengal | India | ||
| 146 | Delhi | India | |||
| 147 | Afula | Israel | |||
| 148 | Haifa | Israel | |||
| 149 | Holon | Israel | |||
| 150 | Jerusalem | Israel | |||
| 151 | Kfar Saba | Israel | |||
| 152 | Ramat Gan | Israel | |||
| 153 | Tel Aviv | Israel | |||
| 154 | Liepaja | Latvia | |||
| 155 | Rezekne | Latvia | |||
| 156 | Valmiera | Latvia | |||
| 157 | Ventspils | Latvia | |||
| 158 | Beirut | Lebanon | |||
| 159 | Arequipa | Peru | |||
| 160 | Cuzco | Peru | |||
| 161 | Lima | Peru | |||
| 162 | Bydgoszcz | Poland | |||
| 163 | Lancut | Poland | |||
| 164 | Lodz | Poland | |||
| 165 | Mielec | Poland | |||
| 166 | Poznan | Poland | |||
| 167 | Pulawy | Poland | |||
| 168 | Engels | Russian Federation | |||
| 169 | Niznhy Novgorod | Russian Federation | |||
| 170 | Novosibirsk | Russian Federation | |||
| 171 | St. Petersburg | Russian Federation | |||
| 172 | Tomsk | Russian Federation | |||
| 173 | Belgrade | Serbia | |||
| 174 | Kragujevac | Serbia | |||
| 175 | Nis | Serbia | |||
| 176 | Novi Sad | Serbia | |||
| 177 | Trnava | Slovakia | |||
| 178 | Middelburg | Mpumalanga | South Africa | ||
| 179 | Bloemfontein | South Africa | |||
| 180 | Dundee | South Africa | |||
| 181 | Durban | South Africa | |||
| 182 | Krugersdorp | South Africa | |||
| 183 | Limpopo | South Africa | |||
| 184 | Port Elizabeth | South Africa | |||
| 185 | Pretoria | South Africa | |||
| 186 | Somerset West | South Africa | |||
| 187 | Worcester | South Africa | |||
| 188 | Chernivci | Ukraine | |||
| 189 | Donetsk | Ukraine | |||
| 190 | Kharkiv | Ukraine | |||
| 191 | Kyiv | Ukraine | |||
| 192 | Odesa | Ukraine | |||
| 193 | Poltava | Ukraine | |||
| 194 | Sumy | Ukraine | |||
| 195 | Vinnytsya | Ukraine | |||
| 196 | Leicester | United Kingdom |
Sponsors and Collaborators
- BioCryst Pharmaceuticals
- Department of Health and Human Services
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00958776
Other Study ID Numbers:
- BCX1812-301
First Posted:
Aug 13, 2009
Last Update Posted:
Feb 12, 2015
Last Verified:
Jan 1, 2015
Keywords provided by BioCryst Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Period Title: Overall Study | ||
| STARTED | 137 | 268 |
| COMPLETED | 121 | 239 |
| NOT COMPLETED | 16 | 29 |
Baseline Characteristics
| Arm/Group Title | Placebo+SOC | Peramivir+SOC | Total |
|---|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. | Total of all reporting groups |
| Overall Participants | 137 | 268 | 405 |
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
43
|
47
|
46
|
| Age, Customized (participants) [Number] | |||
| Children 6-11 Years |
2
1.5%
|
2
0.7%
|
4
1%
|
| Adolescents 12-17 Years |
4
2.9%
|
7
2.6%
|
11
2.7%
|
| Adults 18-24 Years |
23
16.8%
|
33
12.3%
|
56
13.8%
|
| Adults 25-34 Years |
23
16.8%
|
40
14.9%
|
63
15.6%
|
| Adults 35-44 Years |
21
15.3%
|
44
16.4%
|
65
16%
|
| Adults 45-54 Years |
27
19.7%
|
44
16.4%
|
71
17.5%
|
| Adults 55-64 Years |
17
12.4%
|
45
16.8%
|
62
15.3%
|
| Adults 65-74 Years |
11
8%
|
25
9.3%
|
36
8.9%
|
| Adults ≥ 75 Years |
9
6.6%
|
28
10.4%
|
37
9.1%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
67
48.9%
|
132
49.3%
|
199
49.1%
|
| Male |
70
51.1%
|
136
50.7%
|
206
50.9%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Asian |
31
22.6%
|
52
19.4%
|
83
20.5%
|
| White |
71
51.8%
|
169
63.1%
|
240
59.3%
|
| Black, of African Heritage or African American |
23
16.8%
|
28
10.4%
|
51
12.6%
|
| Native Hawaiian or Other Pacific Islander |
1
0.7%
|
1
0.4%
|
2
0.5%
|
| Other |
11
8%
|
18
6.7%
|
29
7.2%
|
| Body mass index (BMI) (kg/m^2) [Mean (Full Range) ] | |||
| Mean (Full Range) [kg/m^2] |
27.7
|
27.5
|
27.6
|
| Supplemental oxygen required at Screening (participants) [Number] | |||
| Needed |
45
32.8%
|
87
32.5%
|
132
32.6%
|
| Not needed |
89
65%
|
177
66%
|
266
65.7%
|
| Missing |
3
2.2%
|
4
1.5%
|
7
1.7%
|
| ICU admission at Baseline (participants) [Number] | |||
| Admitted |
17
12.4%
|
33
12.3%
|
50
12.3%
|
| Not admitted |
117
85.4%
|
231
86.2%
|
348
85.9%
|
| Missing |
3
2.2%
|
4
1.5%
|
7
1.7%
|
| Influenza Vaccination Status (participants) [Number] | |||
| Not vaccinated this year |
111
81%
|
226
84.3%
|
337
83.2%
|
| Vaccinated this year |
26
19%
|
41
15.3%
|
67
16.5%
|
| Missing |
0
0%
|
1
0.4%
|
1
0.2%
|
| Duration of Illness (participants) [Number] | |||
| ≤ 48 hours |
75
54.7%
|
150
56%
|
225
55.6%
|
| > 48 hours |
62
45.3%
|
118
44%
|
180
44.4%
|
| Standard of Care Received (CRF) (participants) [Number] | |||
| NAI-Containing Antiviral Therapy |
89
65%
|
179
66.8%
|
268
66.2%
|
| Non-NAI-Containing Antiviral Therapy |
9
6.6%
|
7
2.6%
|
16
4%
|
| Supportive Care/No Antiviral Therapy |
39
28.5%
|
82
30.6%
|
121
29.9%
|
| Absolute Lymphocyte Count at Baseline (cell count) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cell count] |
1.3
(1.25)
|
1.3
(1.52)
|
1.3
(1.44)
|
| Chest X-ray at Screening (participants) [Number] | |||
| Normal |
88
64.2%
|
148
55.2%
|
236
58.3%
|
| Abnormal |
49
35.8%
|
120
44.8%
|
169
41.7%
|
Outcome Measures
| Title | Time to Clinical Resolution (Kaplan-Meier Estimate) |
|---|---|
| Description | 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). |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain a NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Median (95% Confidence Interval) [hours] |
49.5
|
42.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.973 |
| Comments | ||
| Method | Wilcoxon-Gehan statistic | |
| Comments | Analysis stratified by duration of illness at randomization, ICU status and use of supplemental oxygen at Baseline, influenza season and type. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 1.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio was calculated using a Cox regression model with factors of duration of illness at randomization, ICU status at Baseline, use of supplemental oxygen at Baseline, influenza season, and influenza type. | |
| Title | Change (Reduction) in Influenza Virus Titer |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 24, 48, 108 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 34 | 61 |
| Change from Baseline, 24 Hours |
-1.09
|
-1.49
|
| Change from Baseline, 48 Hours |
-1.67
|
-2.02
|
| Change from Baseline, 108 Hours |
-2.39
|
-2.48
|
| Title | Time to Alleviation of Clinical Symptoms of Influenza |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 77 |
| Median (95% Confidence Interval) [hours] |
68.2
|
67.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.558 |
| Comments | ||
| Method | Wilcoxon-Gehan statistic | |
| Comments | Analysis stratified by duration of illness at randomization, ICU status and use of supplemental oxygen at Baseline, influenza season and type. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio was calculated using a Cox regression model with factors of duration of illness at randomization, ICU status at Baseline, use of supplemental oxygen at Baseline, influenza season, and influenza type. | |
| Title | Time to Resolution of Fever (Kaplan-Meier Estimate) |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Median (95% Confidence Interval) [hours] |
41.0
|
42.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.633 |
| Comments | ||
| Method | Wilcoxon-Gehan statistic | |
| Comments | Analysis stratified by duration of illness at randomization, ICU status and use of supplemental oxygen at Baseline, influenza season and type. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 1.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio was calculated using a Cox regression model with factors of duration of illness at randomization, ICU status at Baseline, use of supplemental oxygen at Baseline, influenza season, and influenza type. | |
| Title | Time to Resumption of Usual Activities |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 42 | 74 |
| Median (95% Confidence Interval) [days] |
9.3
|
8.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.747 |
| Comments | ||
| Method | Wilcoxon-Gehan statistic | |
| Comments | Analysis stratified by duration of illness at randomization, ICU status and use of supplemental oxygen at Baseline, influenza season and type. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.46 | |
| Confidence Interval |
(2-Sided) 95% 0.92 to 2.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio was calculated using a Cox regression model with factors of duration of illness at randomization, ICU status at Baseline, use of supplemental oxygen at Baseline, influenza season, and influenza type. | |
| Title | Number of Subjects With ICU Admission |
|---|---|
| Description | The number of subjects requiring ICU admission post-randomization was summarized by treatment group. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| At Baseline |
8
5.8%
|
15
5.6%
|
| After initiation of treatment |
1
0.7%
|
0
0%
|
| At any time |
9
6.6%
|
15
5.6%
|
| Title | Duration of All ICU Admissions (Kaplan-Meier Estimate) |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Median (95% Confidence Interval) [days] |
3.0
|
3.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.303 |
| Comments | ||
| Method | Wilcoxon-Gehan statistic | |
| Comments | Analysis stratified by duration of illness at randomization, ICU status and use of supplemental oxygen at Baseline, influenza season and type. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) 95% 0.41 to 2.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio is calculated using a Cox regression model with factors of duration of illness at randomization, ICU status at baseline, use of supplemental oxygen at baseline, influenza season, and influenza type. | |
| Title | Time to Hospital Discharge |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Median (95% Confidence Interval) [days] |
5.0
|
5.0
|
| Title | Incidence of Influenza-Related Complications |
|---|---|
| Description | Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis, and pneumonia as reported on the influenza-related complications CRF. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Any Influenza-Related Complication |
9
6.6%
|
15
5.6%
|
| Otitis |
0
0%
|
0
0%
|
| Sinusitis |
1
0.7%
|
2
0.7%
|
| Bronchitis |
4
2.9%
|
5
1.9%
|
| Pneumonia |
4
2.9%
|
8
3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.768 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Analysis stratified by symptom onset prior to randomization, Baseline ICU status, need for supplemental oxygen at Baseline, influenza season and type. | |
| Title | Number of Subjects Requiring More Than 5 Days of Study Drug |
|---|---|
| Description | 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. |
| Time Frame | 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 43 | 78 |
| Number [participants] |
3
2.2%
|
6
2.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo+SOC, Peramivir+SOC |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.758 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Analysis stratified by symptom onset prior to randomization, Baseline ICU status, need for supplemental oxygen at Baseline, influenza season and type. | |
| Title | Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate) |
|---|---|
| Description | 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. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain an NAI at randomization. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 42 | 72 |
| 14 Day Survival |
98
|
100
|
| 28 Day Survival |
98
|
100
|
| Title | Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) |
|---|---|
| Description | 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. |
| Time Frame | Initial (baseline or post-baseline) and up to 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected (ITTI) population included randomized subjects who received at least 1 dose of study drug, and had confirmed influenza A or B. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 116 | 222 |
| A: H3N2-Initial Peramivir Susceptibility |
0.18
(0.074)
|
0.18
(0.044)
|
| A: H3N2-Initial Oseltamivir Susceptibility |
0.30
(0.131)
|
0.31
(0.131)
|
| A: H3N2-Initial Zanamivir Susceptibility |
0.34
(0.185)
|
0.34
(0.071)
|
| A: H1N1- Initial Peramivir Susceptibility |
0.24
(0.152)
|
1.11
(6.181)
|
| A: H1N1- Initial Oseltamivir Susceptibility |
1.12
(0.772)
|
11.03
(70.524)
|
| A: H1N1- Initial Zanamivir Susceptibility |
0.60
(0.416)
|
0.60
(0.402)
|
| B: Initial Peramivir Susceptibility |
1.14
(0.625)
|
1.15
(0.628)
|
| B: Initial Oseltamivir Susceptibility |
18.47
(4.830)
|
21.47
(9.422)
|
| B: Initial Zanamivir Susceptibility |
2.36
(1.009)
|
2.30
(0.958)
|
| Title | Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial |
|---|---|
| Description | 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. |
| Time Frame | Initial (baseline or post-baseline) and up to 10 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat Infected (ITTI) population included randomized subjects who received at least 1 dose of study drug, and had confirmed influenza A or B. |
| Arm/Group Title | Placebo+SOC | Peramivir+SOC |
|---|---|---|
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. |
| Measure Participants | 116 | 222 |
| A: H3N2-Fold Change in Peramivir Susceptibility |
1.23
(0.555)
|
1.19
(0.527)
|
| A: H3N2-Fold Change in Oseltamivir Susceptibility |
1.36
(0.836)
|
1.14
(0.805)
|
| A: H3N2-Fold Change in Zanamivir Susceptibility |
2.70
(6.563)
|
1.33
(0.773)
|
| A: H1N1-Fold Change in Peramivir Susceptibility |
1.12
(0.879)
|
3.63
(16.333)
|
| A: H1N1-Fold Change in Oseltamivir Susceptibility |
1.51
(1.695)
|
9.20
(50.920)
|
| A: H1N1-Fold Change in Zanamivir Susceptibility |
1.03
(0.728)
|
1.06
(0.490)
|
| B: Fold Change in Peramivir Susceptibility |
1.01
(0.331)
|
3.21
(8.456)
|
| B: Fold Change in Oseltamivir Susceptibility |
0.98
(0.376)
|
1.48
(1.635)
|
| B: Fold Change in Zanamivir Susceptibility |
1.02
(0.375)
|
1.36
(0.613)
|
Adverse Events
| Time Frame | Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm). | |||
| Arm/Group Title | Placebo+SOC | Peramivir+SOC | ||
| Arm/Group Description | Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. | 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. | ||
All Cause Mortality |
||||
| Placebo+SOC | Peramivir+SOC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo+SOC | Peramivir+SOC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/134 (9.7%) | 15/264 (5.7%) | ||
| Cardiac disorders | ||||
| Cardiac Failure Congestive | 0/134 (0%) | 2/264 (0.8%) | ||
| Gastrointestinal disorders | ||||
| Haematemesis | 1/134 (0.7%) | 0/264 (0%) | ||
| General disorders | ||||
| Chest Pain | 0/134 (0%) | 1/264 (0.4%) | ||
| Multi-organ Disorder | 1/134 (0.7%) | 0/264 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 2/134 (1.5%) | 2/264 (0.8%) | ||
| Klebsiella Bacteraemia | 0/134 (0%) | 1/264 (0.4%) | ||
| Sinusitis Bacterial | 0/134 (0%) | 1/264 (0.4%) | ||
| Cellulitis | 2/134 (1.5%) | 0/264 (0%) | ||
| Echinococciasis | 1/134 (0.7%) | 0/264 (0%) | ||
| Influenza | 1/134 (0.7%) | 0/264 (0%) | ||
| Respiratory Tract Infection Viral | 1/134 (0.7%) | 0/264 (0%) | ||
| Septic Shock | 1/134 (0.7%) | 0/264 (0%) | ||
| Viral Myositis | 1/134 (0.7%) | 0/264 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Accidental Needle Stick | 1/134 (0.7%) | 0/264 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetic Ketoacidosis | 0/134 (0%) | 1/264 (0.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal Chest Pain | 0/134 (0%) | 1/264 (0.4%) | ||
| Back Pain | 1/134 (0.7%) | 0/264 (0%) | ||
| Nervous system disorders | ||||
| Neuroleptic Malignant Syndrome | 0/134 (0%) | 1/264 (0.4%) | ||
| Presyncope | 0/134 (0%) | 1/264 (0.4%) | ||
| Psychiatric disorders | ||||
| Confusional State | 0/134 (0%) | 1/264 (0.4%) | ||
| Delirium | 0/134 (0%) | 1/264 (0.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Distress Syndrome | 0/134 (0%) | 2/264 (0.8%) | ||
| Chronic Obstructive Pulmonary Disease | 2/134 (1.5%) | 2/264 (0.8%) | ||
| Acute Respiratory Failure | 0/134 (0%) | 1/264 (0.4%) | ||
| Dyspnoea | 0/134 (0%) | 1/264 (0.4%) | ||
| Respiratory Arrest | 1/134 (0.7%) | 0/264 (0%) | ||
| Vascular disorders | ||||
| Haemodynamic Instability | 1/134 (0.7%) | 0/264 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo+SOC | Peramivir+SOC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/134 (31.3%) | 63/264 (23.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/134 (2.2%) | 5/264 (1.9%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 10/134 (7.5%) | 12/264 (4.5%) | ||
| Nausea | 10/134 (7.5%) | 10/264 (3.8%) | ||
| Constipation | 7/134 (5.2%) | 6/264 (2.3%) | ||
| Vomiting | 5/134 (3.7%) | 3/264 (1.1%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 5/134 (3.7%) | 7/264 (2.7%) | ||
| Blood Creatine Phosphokinase Increased | 1/134 (0.7%) | 7/264 (2.7%) | ||
| Aspartate Aminotransferase Increased | 3/134 (2.2%) | 6/264 (2.3%) | ||
| Blood Glucose Increased | 3/134 (2.2%) | 5/264 (1.9%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 5/134 (3.7%) | 8/264 (3%) | ||
| Hypophosphataemia | 3/134 (2.2%) | 2/264 (0.8%) | ||
| Dehydration | 3/134 (2.2%) | 1/264 (0.4%) | ||
| Hypomagnesaemia | 4/134 (3%) | 1/264 (0.4%) | ||
| Nervous system disorders | ||||
| Headache | 2/134 (1.5%) | 7/264 (2.7%) | ||
| Dizziness | 3/134 (2.2%) | 1/264 (0.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/134 (0.7%) | 10/264 (3.8%) | ||
| Anxiety | 3/134 (2.2%) | 5/264 (1.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Epistaxis | 4/134 (3%) | 4/264 (1.5%) | ||
| Vascular disorders | ||||
| Hypertension | 1/134 (0.7%) | 7/264 (2.7%) | ||
Limitations/Caveats
Interim analysis of the primary efficacy endpoint (time to clinical resolution) performed after the end of the 2012 Southern Hemisphere influenza season lead to study termination for futility. Final enrollment was ~70% of the planned enrollment.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | William P. Sheridan, MBBS |
|---|---|
| Organization | BioCryst Pharmaceuticals, Inc. |
| Phone | 919-859-1302 |
Responsible Party:
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00958776
Other Study ID Numbers:
- BCX1812-301
First Posted:
Aug 13, 2009
Last Update Posted:
Feb 12, 2015
Last Verified:
Jan 1, 2015