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

NCT ID: NCT02287467

Last Updated: 2019-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 329 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-06-07

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.

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.

Conditions

Influenza A; Influenza B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Intravenous hyperimmune immunoglobulin (IVIG)

Intervention Type: 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 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.

Group Type: PLACEBO_COMPARATOR

Placebo for IVIG

Intervention Type: BIOLOGICAL

Administered IV as 500 mL of normal saline

Interventions

Intravenous hyperimmune immunoglobulin (IVIG)

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)

Intervention Type: BIOLOGICAL

Placebo for IVIG

Administered IV as 500 mL of normal saline

Intervention Type: BIOLOGICAL

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: collaborator

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard T. Davey, Jr., MD

Role: STUDY_CHAIR

National Institute of Allergy and Infectious Diseases (NIAID)

Eduardo Fernández-Cruz, MD, PhD

Role: STUDY_CHAIR

Hospital General Universitario Gregorio Marañón

Norman P. Markowitz, MD

Role: STUDY_CHAIR

The Henry Ford Hospital

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

Role: STUDY_CHAIR

University College, London

Locations

UCSD Antiviral Research Center (A VRC)

San Diego, California, United States

Denver Public Health

Denver, Colorado, United States

University of Illinois

Chicago, Illinois, United States

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Henry Ford Hospital

Detroit, Michigan, United States

Minneapolis VA Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Cooper University Hospital

Camden, New Jersey, United States

Cornell CRS

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Case Western Reserve University

Cleveland, Ohio, United States

OHIO State University (OSU) Wexner Medical Center

Columbus, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

West Virginia University

Morgantown, West Virginia, United States

Westmead Hospital

Sydney, , Australia

Odense University Hospital

Odense, , Denmark

St James's University Hospital

Leeds, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Countries

United States; Australia; Denmark; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37289541 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31582358 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

INSIGHT 006: FLU-IVIG

Identifier Type: -

Identifier Source: org_study_id