Clinical trial NCT02287467: Evaluating the Safety and Efficacy of Anti-Influenza Intravenous Hyperimmune Immunoglobulin (IVIG) in Adults Hospitalized With Influenza
Official title: Anti-Influenza Hyperimmune Intravenous Immunoglobulin Clinical Outcome Study (INSIGHT 006: FLU-IVIG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza A
Influenza B
Keywords: Antiviral
IVIG
Hemagglutination inhibition (HAI)
Antibody
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: University of Minnesota
name: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
First posted: 2014-11-10
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of Patients in Each of 6 Clinical Status Categories on Day 7
timeFrame: Assessed on Day 7
Secondary outcomes:
measure: Number of Patients in Each of 5 Clinical Status Categories on Day 3
timeFrame: Assessed on Day 3
measure: Number of Patients in Each of 6 Clinical Status Categories on Day 3
timeFrame: Measured on Day 3
measure: Number of Patients With a Favorable Outcome on Day 7
timeFrame: Assessed on Day 7
measure: Hospital Discharge
timeFrame: Measured through Day 7
measure: Mortality
timeFrame: Measured through day 28
measure: Number of Patients Alive and Out of Hospital
timeFrame: Measured through Day 28
measure: Change in Viral Load
timeFrame: Day 3
measure: Death or Re-hospitalization
timeFrame: Day 28
measure: Percent of Participants Developing Complications
timeFrame: Measured through Day 28
measure: Number of Patients in Each of 6 Clinical Status Categories on Day 14
timeFrame: Measured on day 14
measure: Number of Patients Alive and Out of Hospital on Day 14
timeFrame: day 14
measure: Resumption of Normal Activities by Day 14
timeFrame: day 14
measure: Number of Patients in Each of 6 Clinical Status Categories on Day 28
timeFrame: day 28
measure: Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7
timeFrame: Day 7
measure: Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7
timeFrame: Day 7
measure: pH1N1 Titers at Day 7
timeFrame: Day 7
measure: H3N2 Titers at Day 7
timeFrame: Day 7
measure: Influenza B Titers at Day 7
timeFrame: Day 7
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Antiviral Research Center (A VRC)
state: California
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Cornell CRS
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: OHIO State University (OSU) Wexner Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Sydney
country: Australia
facility: Westmead Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Richard T. Davey, Jr., MD
role: STUDY_CHAIR
affiliation: Hospital General Universitario Gregorio Marañón
name: Eduardo Fernández-Cruz, MD, PhD
role: STUDY_CHAIR
affiliation: The Henry Ford Hospital
name: Norman P. Markowitz, MD
role: STUDY_CHAIR
affiliation: University College, London
name: Sarah L. Pett, MD, MBBS, DTM, MRCP (UK)
role: STUDY_CHAIR
References:
citation: 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.