Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A
- Conditions
- Influenza A H3N2Influenza A H1N1
- Interventions
- Biological: FLU-IGIVOther: Placebo for FLU-IGIV
- Registration Number
- NCT03315104
- Lead Sponsor
- Emergent BioSolutions
- Brief Summary
Influenza, or the flu, is an infectious respiratory disease that can range in severity from mild to severe to even death. This study aims to evaluate a treatment for people who are hospitalized with the flu. The study is looking to see if antibodies collected from people who have recovered from the seasonal flu or who have had the seasonal flu shot can be used safely as a study drug to treat hospitalized patients with severe flu infections. Also, this study will help to find the right dose for this study drug for treatment of severe flu in hospitalized patients. Overall, this study will evaluate if the hospitalized patients receiving standard of care along with the study drug get better more quickly than those treated with standard of care and placebo. The study drug that contains antibodies against the flu is called anti-influenza immunoglobulin intravenous (FLU-IGIV).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
- Provision of voluntary informed consent in writing by patient, or legally authorized representative.
- Age ≥ 18 years of age.
- Locally determined positive influenza A infection (Rapid Antigen (Ag) Test or PCR) from a specimen obtained within 2 days prior to randomization.
- Onset of symptoms ≤ 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom or fever.
- Hospitalized (or in observation unit) with influenza, with anticipated hospitalization for more than 24 hours and will be/already are receiving antiviral SOC.
- Experiencing ≥ 1 respiratory symptom (ex. cough, sore throat, nasal congestion) and ≥ 1 constitutional symptom (ex. headache, myalgia, feverishness or fatigue).
- For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 60 of the study.
- Willingness to have blood and respiratory samples obtained and stored.
- National Early Warning Score (NEW score) ≥ 3 at screening.
- Use of any investigational product within the past 30 days prior to screening.
- History of hypersensitivity to blood or plasma products (as judged by the site investigator).
- History of allergy to latex or rubber.
- Known medical history of IgA deficiency.
- Pregnancy or lactation.
- Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the patient (e.g. decompensated congestive heart failure), based on investigator's medical opinion with careful consideration of lab results.
- Liver function: liver function test (LFT) > 2.5 times upper limit of normal (ULN).
- Renal Function: glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 (age and sex adjusted).
- A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g. cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy).
- An opinion of the investigator that it would be unwise to allow participation of the patient in the study (the reason for exclusion of the patient must be documented).
- Receiving extracorporeal membrane oxygenation (ECMO).
- Anticipated life expectancy of < 90 days.
- Confirmed bacterial pneumonia or any concurrent respiratory viral infection that is not influenza A (ex. respiratory syncytial virus (RSV) infection).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FLU-IGIV High Dose FLU-IGIV Participants will receive a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive standard of care (SOC) antiviral treatment for flu. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration. FLU-IGIV Low Dose FLU-IGIV Participants will receive a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive SOC antiviral treatment for flu. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration. FLU-IGIV Placebo Placebo for FLU-IGIV Participants will receive a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Participants will also receive SOC antiviral treatment for flu. Administered IV as 500 mL of normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
- Primary Outcome Measures
Name Time Method Frequency Counts and Percentage of Subjects With Adverse Events Measured through Day 60 Frequency counts and percentage of subjects with Adverse Events by severity
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay Measured through 48 Hours post-dose Levels of anti-influenza A antibodies circulating in blood over time. We initially intended to look at this variable through Day 8, however, potential native antibody level changes and sparse sampling confounded results from 0 to 48 hours post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8. For AUC from time 0 to 48 hours, subjects who did not have a sample collected within +/-10% of 48 hours post-dose had this parameter set to missing, which is why the number of subjects who contributed data for this outcome measure is lower than the overall number of subjects analyzed.
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay Measured through Day 8 post-dose Maximum observed concentration (reported as a titer) of anti-influenza A antibodies measured from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8.
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay Measured through Day 8 post-dose Time that anti-influenza A antibodies are at maximum concentration from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8.
The rate of study drug elimination and dependent parameters were not accurately estimable due to rising or sustained levels of anti-influenza A antibodies, this includes First Order Terminal Elimination Rate Constant \[Kel\], Plasma Clearance \[Cl\] and Total Volume of Distribution \[Vz\].
- Secondary Outcome Measures
Name Time Method Ordinal Scale Subject Distribution Reflecting Clinical Status At Day 8 post-dose Score (physician-assessed): 1=death; 2=hospitalization in the intensive care unit (ICU); 3=non-ICU hospitalization requiring supplemental oxygen; 4=non-ICU hospitalization not requiring supplemental oxygen; 5=no longer hospitalized but unable to resume normal activities; 6=no longer hospitalized with full resumption of normal activities. A higher score reflects improved clinical status. Not all ITT subjects had ordinal scale data available at Day 8 post-dose which explains why the overall number of participants analyzed is not consistent with the overall number of subjects included at baseline. For subjects who were discharged with unknown ordinal score the more conservative of two relevant discharged categories was imputed.
Trial Locations
- Locations (55)
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Michael E. DeBakey VA Medical Center
🇺🇸Houston, Texas, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Baptist Health Center for Clinical Research
🇺🇸Little Rock, Arkansas, United States
Denver public Health
🇺🇸Denver, Colorado, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Atlanta Institute for Medical Research Inc.
🇺🇸Atlanta, Georgia, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
MultiCare Institute for Research & Innovation
🇺🇸Tacoma, Washington, United States
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Providence-Providence Park Hospital, Southfield
🇺🇸Southfield, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
St Luke's University Health Network
🇺🇸Bethlehem, Pennsylvania, United States
Wayne State University/Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Premier Health Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Pulmonlx LLC Pulmonary & Critical Care Medicine
🇺🇸Greensboro, North Carolina, United States
CISSS BSL/Hopital Regional de Rimouski
🇨🇦Rimouski, Quebec, Canada
San Cristobal Hospital
🇵🇷Ponce, Puerto Rico
Health Sciences Center
🇨🇦Winnipeg, Manitoba, Canada
Regional Health
🇺🇸Rapid City, South Dakota, United States
Carilion Medical Center
🇺🇸Roanoke, Virginia, United States
Mayaguez Medical Center
🇵🇷Mayagüez, Puerto Rico
Grace Hospital
🇨🇦Winnipeg, Manitoba, Canada
Hospital Universitari Mutua Terrassa
🇪🇸Barcelona, Spain
Reina Sofia University Hospital
🇪🇸Córdoba, Spain
Hospital Universitari de Tarragona Joan XXIII
🇪🇸Tarragona, Spain
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
UT Health San Antonio
🇺🇸San Antonio, Texas, United States
Wayne State University/Sinai Grace Hospital
🇺🇸Detroit, Michigan, United States
University of Utah HealthCare
🇺🇸Salt Lake City, Utah, United States
St. Boniface Hospital
🇨🇦Winnipeg, Manitoba, Canada
HonorHealth
🇺🇸Scottsdale, Arizona, United States
University of California, Irvine Emergency Medicine
🇺🇸Orange, California, United States
Christiana Care Health Systems
🇺🇸Newark, Delaware, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Hospital Clinic of Barcelona
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Ciusss McQ
🇨🇦Trois-Rivières, Quebec, Canada
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas medical Center
🇺🇸Kansas City, Kansas, United States