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

Influenza A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287467
• Other study ID #: INSIGHT 006: FLU-IVIG
• Status: Completed
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: June 7, 2018

Study information

• Verified date: November 2019
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: June 7, 2018
• Est. primary completion date: June 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Influenza A
• Influenza B
• Influenza, Human

Intervention

Biological:
• 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)
• Placebo for IVIG
Administered IV as 500 mL of normal saline

Locations

Country	Name	City	State
Australia	Westmead Hospital	Sydney
Denmark	Odense University Hospital	Odense
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Churchill Hospital	Oxford
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	University of Illinois	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	OHIO State University (OSU) Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Denver Public Health	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Cornell CRS	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSD Antiviral Research Center (A VRC)	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), University of Minnesota

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  United Kingdom, 

Outcome

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