Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza

Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)

Influenza (the flu) is a common illness that usually occurs in autumn and winter. The flu is usually mild, but can cause serious illness or death. The purpose of this study is to test the safety and effectiveness of an antibody against the flu (called intravenous hyperimmune immunoglobulin or IVIG) in people who are hospitalized for severe flu.

Study Overview

Detailed Description

Influenza is responsible for thousands of hospitalizations and deaths each year in the United States and worldwide. One possible new treatment for the flu involves the use of IVIG, a blood product containing antibodies from people who have recovered from the flu or who have had a flu shot. The purpose of this study is to evaluate whether IVIG can reduce the severity and duration of flu in people who are hospitalized with the flu.

The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days.

At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours.

On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat.

Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.

Study Type

Interventional

Enrollment (Actual)

329

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sydney, Australia
        • Westmead Hospital
      • Odense, Denmark
        • Odense University Hospital
      • Leeds, United Kingdom
        • St James's University Hospital
      • Oxford, United Kingdom
        • Churchill Hospital
    • California
      • San Diego, California, United States, 92103
        • UCSD Antiviral Research Center (A VRC)
    • Colorado
      • Denver, Colorado, United States, 80204
        • Denver public Health
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • New York, New York, United States, 10010
        • Cornell CRS
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43210
        • Ohio State University (OSU) Wexner Medical Center
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75235
        • UT Southwestern Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent
  • Locally determined positive influenza test (by polymerase chain reaction [PCR] or other nucleic acid test, or by rapid antigen [Ag]) from a specimen obtained within 2 days prior to randomization
  • Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
  • Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
  • For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
  • Willingness to have blood and respiratory samples obtained and stored
  • NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)

Exclusion Criteria:

  • Women who are pregnant or breast-feeding
  • Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
  • Prior treatment with any investigational drug therapy within 30 days prior to screening
  • History of allergic reaction to blood or plasma products (as judged by the site investigator)
  • Known immunoglobulin A (IgA) deficiency
  • A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
  • Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study
  • Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
  • Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure)
  • Receiving extracorporeal membrane oxygenation (ECMO)
  • Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: hIVIG
Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
Placebo Comparator: Arm B: Placebo
Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Administered IV as 500 mL of normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients in Each of 6 Clinical Status Categories on Day 7
Time Frame: Assessed on Day 7
This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).
Assessed on Day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients in Each of 5 Clinical Status Categories on Day 3
Time Frame: Assessed on Day 3
5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).
Assessed on Day 3
Number of Patients in Each of 6 Clinical Status Categories on Day 3
Time Frame: Measured on Day 3
6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).
Measured on Day 3
Number of Patients With a Favorable Outcome on Day 7
Time Frame: Assessed on Day 7
Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.
Assessed on Day 7
Hospital Discharge
Time Frame: Measured through Day 7
Number of participants alive and discharged from the hospital
Measured through Day 7
Mortality
Time Frame: Measured through day 28
Number of participants dying through day 28.
Measured through day 28
Number of Patients Alive and Out of Hospital
Time Frame: Measured through Day 28
Number and percent alive and out of hospital on day 28
Measured through Day 28
Change in Viral Load
Time Frame: Day 3
Change in nasopharyngeal viral load from baseline to day 3
Day 3
Death or Re-hospitalization
Time Frame: Day 28
Number and percent of participants who died or were re-hospitalized after initial discharge
Day 28
Percent of Participants Developing Complications
Time Frame: Measured through Day 28
Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis
Measured through Day 28
Number of Patients in Each of 6 Clinical Status Categories on Day 14
Time Frame: Measured on day 14
6-category ordinal outcome measured on day 14
Measured on day 14
Number of Patients Alive and Out of Hospital on Day 14
Time Frame: day 14
Number and percentage of participants alive and out of the hospital on Day 14
day 14
Resumption of Normal Activities by Day 14
Time Frame: day 14
Participants reporting resumption of normal daily activities by Day 14
day 14
Number of Patients in Each of 6 Clinical Status Categories on Day 28
Time Frame: day 28
6-category ordinal outcome corresponding to clinical status on day 28
day 28
Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Time Frame: Day 7
Primary 6-category ordinal outcome for participants infected with Influenza A
Day 7
Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Time Frame: Day 7
Primary 6-category ordinal outcome for subgroup of participants infected with influenza B
Day 7
pH1N1 Titers at Day 7
Time Frame: Day 7
pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus
Day 7
H3N2 Titers at Day 7
Time Frame: Day 7
H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus
Day 7
Influenza B Titers at Day 7
Time Frame: Day 7
Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus
Day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Richard T. Davey, Jr., MD, National Institute of Allergy and Infectious Diseases (NIAID)
  • Study Chair: Eduardo Fernández-Cruz, MD, PhD, Hospital General Universitario Gregorio Marañon
  • Study Chair: Norman P. Markowitz, MD, The Henry Ford Hospital
  • Study Chair: Sarah L. Pett, MD, MBBS, DTM, MRCP (UK), University College, London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

June 7, 2018

Study Completion (Actual)

June 7, 2018

Study Registration Dates

First Submitted

November 6, 2014

First Submitted That Met QC Criteria

November 6, 2014

First Posted (Estimate)

November 10, 2014

Study Record Updates

Last Update Posted (Actual)

November 14, 2019

Last Update Submitted That Met QC Criteria

November 11, 2019

Last Verified

November 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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