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

NCT02287467 | Completed Phase 3 Results DMC

• 1 other identifier: INSIGHT 006: FLU-IVIG
• Study Type: interventional
• Target: 329
• Locations: 4 countries
• Sites: 21

Brief Summary

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.

Conditions

Influenza A; Influenza B

Keywords

Antiviral; IVIG; Hemagglutination inhibition (HAI); Antibody

Outcome Measures

Primary Outcomes (1)

• Number of Patients in Each of 6 Clinical Status Categories 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 Outcomes (18)

• Number of Patients in Each of 5 Clinical Status Categories on Day 3

  Assessed on Day 3

• Number of Patients in Each of 6 Clinical Status Categories on Day 3

  Measured on Day 3

• Number of Patients With a Favorable Outcome on Day 7

  Assessed on Day 7

• Hospital Discharge

  Measured through Day 7

• Mortality

  Measured through day 28

Study Arms (2)

Arm A: hIVIG

EXPERIMENTAL

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.

Biological: Intravenous hyperimmune immunoglobulin (IVIG)

Arm B: Placebo

PLACEBO COMPARATOR

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.

Biological: Placebo for IVIG

Interventions

Intravenous hyperimmune immunoglobulin (IVIG) BIOLOGICAL

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)

Arm A: hIVIG

Placebo for IVIG BIOLOGICAL

Administered IV as 500 mL of normal saline

Arm B: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• University of Minnesota: collaborator
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): collaborator

Study Sites (21)

UCSD Antiviral Research Center (A VRC)

San Diego, California, 92103, United States

Location

Denver Public Health

Denver, Colorado, 80204, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Minneapolis VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Cornell CRS

New York, New York, 10010, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

OHIO State University (OSU) Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Westmead Hospital

Sydney, Australia

Location

Odense University Hospital

Odense, Denmark

Location

St James's University Hospital

Leeds, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (2)

• Vanderven HA, Wentworth DN, Han WM, Peck H, Barr IG, Davey RT Jr, Beigel JH, Dwyer DE, Jain MK, Angus B, Brandt CT, Mykietiuk A, Law MG, Neaton JD, Kent SJ; INSIGHT FLU-IVIG Study Group. Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza. JCI Insight. 2023 Jul 24;8(14):e167464. doi: 10.1172/jci.insight.167464.

  PMID: 37289541 DERIVED

• Davey RT Jr, Fernandez-Cruz E, Markowitz N, Pett S, Babiker AG, Wentworth D, Khurana S, Engen N, Gordin F, Jain MK, Kan V, Polizzotto MN, Riska P, Ruxrungtham K, Temesgen Z, Lundgren J, Beigel JH, Lane HC, Neaton JD; INSIGHT FLU-IVIG Study Group. Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial. Lancet Respir Med. 2019 Nov;7(11):951-963. doi: 10.1016/S2213-2600(19)30253-X. Epub 2019 Sep 30.

  PMID: 31582358 DERIVED

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Richard Davey
• Organization: NIAID

rdavey@niaid.nih.gov

301-496-8029

Study Officials

• Richard T. Davey, Jr., MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  STUDY CHAIR

• Eduardo Fernández-Cruz, MD, PhD

  Hospital General Universitario Gregorio Marañón

  STUDY CHAIR

• Norman P. Markowitz, MD

  The Henry Ford Hospital

  STUDY CHAIR

• Sarah L. Pett, MD, MBBS, DTM, MRCP (UK)

  University College, London

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 10, 2014
• Study Start: January 1, 2015
• Primary Completion: June 7, 2018
• Study Completion: June 7, 2018
• Last Updated: November 14, 2019
• Results First Posted: November 14, 2019

Record last verified: 2019-11

Locations

US (17); GB (2); DK (1); AU (1)