Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A

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

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).

Study Overview

• Status: Completed
• Conditions: Influenza A H3N2; Influenza A H1N1
• Intervention / Treatment: Biological: FLU-IGIV; Other: Placebo for FLU-IGIV

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Center
    • Winnipeg, Manitoba, Canada, R3J 3M7
      • Grace Hospital
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • St. Boniface Hospital
  • Quebec
    • Rimouski, Quebec, Canada, G5L 5T1
      • CISSS BSL/Hopital Regional de Rimouski
    • Trois-Rivières, Quebec, Canada, G8Z 3R9
      • Ciusss McQ
• Puerto Rico
  • Mayagüez, Puerto Rico, 00680
    • Mayaguez Medical Center
  • Ponce, Puerto Rico, 00780
    • San Cristobal Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic of Barcelona
  • Barcelona, Spain, 08036
    • Hospital Del Mar
  • Barcelona, Spain, 08225
    • Hospital Universitari Mútua Terrassa
  • Córdoba, Spain, 14004
    • Reina Sofia University Hospital
  • Tarragona, Spain, 43007
    • Hospital Universitari de Tarragona Joan XXIII
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine Emergency Medicine
  • Colorado
    • Denver, Colorado, United States, 80212
      • Denver public Health
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School Of Medicine
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health Systems
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Atlanta, Georgia, United States, 30350
      • Atlanta Institute for Medical Research Inc.
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Detroit Receiving Hospital
    • Detroit, Michigan, United States, 48202
      • Wayne State University/Sinai Grace Hospital
    • Southfield, Michigan, United States, 48075
      • Providence-Providence Park Hospital, Southfield
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 985400
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Pulmonlx LLC Pulmonary & Critical Care Medicine
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Premier Health Miami Valley Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St Luke's University Health Network
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Regional Health
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 77030
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Healthcare
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research & Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FLU-IGIV High Dose; 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.	Biological: FLU-IGIV; Single dose, sterile liquid formulation for IV administration.; Other Names: Anti-influenza immunoglobulin intravenous (Human); NP-025
Experimental: FLU-IGIV Low Dose; 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.	Biological: FLU-IGIV; Single dose, sterile liquid formulation for IV administration.; Other Names: Anti-influenza immunoglobulin intravenous (Human); NP-025
Placebo Comparator: FLU-IGIV Placebo; 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.	Other: Placebo for FLU-IGIV; Single dose, normal saline solution for IV administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency Counts and Percentage of Subjects With Adverse Events	Frequency counts and percentage of subjects with Adverse Events by severity	Measured through Day 60
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay	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.	Measured through 48 Hours post-dose
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay	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.	Measured through Day 8 post-dose
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay	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].	Measured through Day 8 post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal Scale Subject Distribution Reflecting Clinical Status	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.	At Day 8 post-dose

Collaborators and Investigators

• Sponsor: Emergent BioSolutions
• Investigators: Study Director: Christine Hall, Emergent BioSolutions Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): June 17, 2019
• Study Completion (Actual): June 17, 2019

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: hospitalized; flu; H1N1; serious illness; influenza A; H3N2; human flu; respiratory tract infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: IA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Post results and upload the supporting information.
• IPD Sharing Time Frame: Within 1 year after the study's Primary Completion Date (Last Subject Last Visit).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No