Clinical trial NCT03315104: Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A
Official title: A Randomized, Double-Blind, Placebo-Controlled Dose Ranging Study Evaluating Safety, Pharmacokinetics and Clinical Benefit of FLU-IGIV in Hospitalized Patients With Serious Influenza A Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A H3N2
Influenza A H1N1
Keywords: influenza A
hospitalized
H1N1
H3N2
human flu
respiratory tract infection
serious illness
flu
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
First posted: 2017-10-19
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Staggered enrollment for the first 9 subjects, then parallel low and high dose treatment with a placebo group
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Frequency Counts and Percentage of Subjects With Adverse Events
timeFrame: Measured through Day 60
measure: Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay
timeFrame: Measured through 48 Hours post-dose
measure: Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay
timeFrame: Measured through Day 8 post-dose
measure: Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay
timeFrame: Measured through Day 8 post-dose
Secondary outcomes:
measure: Ordinal Scale Subject Distribution Reflecting Clinical Status
timeFrame: At Day 8 post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Orange
country: United States
facility: University of California, Irvine Emergency Medicine
state: California
city: Denver
country: United States
facility: Denver public Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Systems
state: Delaware
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Institute for Medical Research Inc.
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas medical Center
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Sinai Grace Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence-Providence Park Hospital, Southfield
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Greensboro
country: United States
facility: Pulmonlx LLC Pulmonary & Critical Care Medicine
state: North Carolina
city: Dayton
country: United States
facility: Premier Health Miami Valley Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Bethlehem
country: United States
facility: St Luke's University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Regional Health
state: South Dakota
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah HealthCare
state: Utah
city: Roanoke
country: United States
facility: Carilion Medical Center
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Winnipeg
country: Canada
facility: Health Sciences Center
state: Manitoba
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Grace Hospital
state: Manitoba
city: Rimouski
country: Canada
facility: CISSS BSL/Hopital Regional de Rimouski
state: Quebec
city: Trois-Rivières
country: Canada
facility: Ciusss McQ
state: Quebec
city: Mayagüez
country: Puerto Rico
facility: Mayaguez Medical Center
city: Ponce
country: Puerto Rico
facility: San Cristobal Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Mutua Terrassa
city: Córdoba
country: Spain
facility: Reina Sofia University Hospital
city: Tarragona
country: Spain
facility: Hospital Universitari de Tarragona Joan XXIII
Study officials:
affiliation: Emergent BioSolutions Inc
name: Christine Hall
role: STUDY_DIRECTOR
References: