Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)

Condition(s) targeted: Influenza

Intervention: Intravenous hyperimmune immunoglobulin (Flu-IVIG) (Biological)

Phase: Phase 1

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Richard Davey, MD, Study Chair, Affiliation: National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892
Norman Markowitz, MD, Study Chair, Affiliation: The Henry Ford Hospital, Detroit, MI 48202

The purpose of this randomized, double-blind, placebo-controlled trial of intravenous hyperimmune immunoglobulin (Flu-IVIG) in individuals with influenza A or B is to determine the pharmacokinetic (PK) profile of Flu-IVIG and assess whether antibody levels observed following Flu-IVIG transfusion are similar to those predicted. This pilot study will inform a larger study that will be powered to compare Flu-IVIG with placebo for efficacy.

Official title: Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Hemagglutination Inhibition (HAI) titer for each influenza strain (H1N1, H3N2, B) taken 1 hour postinfusion compared to predicted levels.

Secondary outcome: Compare HAI titers in active drug versus placebo recipients at 1 hour post-infusion, and Study Days 1, 3, and 7 according to the strain and subtype of virus with which participants are infected

Detailed description: The purpose of this randomized, double-blind, placebo-controlled trial of intravenous hyperimmune immunoglobulin (Flu-IVIG) in individuals with influenza A or B is to determine the pharmacokinetic (PK) profile of Flu-IVIG and assess whether antibody levels observed following Flu-IVIG transfusion are similar to those predicted. This pilot study will inform a larger study that will be powered to compare Flu-IVIG with placebo for efficacy. In addition to informing the Flu-IVIG dosing required for the clinical outcomes trial, the pilot study will compare influenza antibody levels and safety for study participants randomly assigned Flu-IVIG and those assigned placebo, assess the feasibility of enrollment, evaluate randomization and blinding procedures, and possibly obtain some preliminary data on efficacy that may be used to inform sample size and study procedures for the clinical outcomes study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

1. Signed informed consent 2. Age greater than or equal to 18 years of age 3. Outpatients or inpatients who are PCR or rapid Ag positive for influenza A or B preferably within 24 hours and no later than 6 days from symptom onset 4. Onset of illness no more than 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom, constitutional symptom or fever 5. For women of child-bearing potential, a negative pregnancy test within one day prior to randomization and a willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 28 of the study 6. Willingness to have blood and respiratory samples obtained and stored EXCLUSION CRITERIA: 1. If hospitalized, admitted for reasons other than influenza or complications of influenza 2. Women who are pregnant or breast-feeding 3. Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin. 4. Prior treatment with any investigational drug therapy within 30 days prior to screening 5. History of allergic reaction to blood or plasma products (as judged by the investigator) 6. Known IgA deficiency 7. A pre-existing condition or use of medication that, in the opinion of the investigator, may place the individual at a substantially increased risk of thrombosis (e. g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy) 8. Serum creatinine greater than or equal to 1. 5 x ULN or known active kidney disease that may affect drug pharmacokinetics (e. g., nephrotic syndrome) 9. Presence of any pre-existing illness that, in the opinion of the investigator, would place the individual at an unreasonably increased risk through participation in this study 10. Patients who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol 11. Medical conditions for which receipt of 500mL volume may be dangerous to the patient (e. g., decompensated congestive heart failure) 12. Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e. g., H5N1, H7N9)

University of California at San Diego, San Diego, California 92103, United States

Denver Public Health, Denver, Colorado 80204, United States

George Washington University, Washington, District of Columbia 20037, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States

Henry Ford Hospital, Detroit, Michigan 48202, United States

Mayo Clinic, Rochester, Minnesota 55905, United States

Cooper University Hospital, Camden, New Jersey 08103, United States

Montefiore Medical Center, Bronx, New York 10467, United States

Ohio State University Wexner Medical Center, Columbus, Ohio 43210, United States

Miami Valley Hospital, Dayton, Ohio 45409, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75235, United States

NIH Clinical Center Detailed Web Page

Related publications:

Dwyer DE; INSIGHT Influenza Study Group. Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies. Vaccine. 2011 Jul 22;29 Suppl 2:B56-62. doi: 10.1016/j.vaccine.2011.04.105.

Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. Epub 2006 Aug 29.

Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quiñones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, Higuera A, Mondragon E, Cordova-Villalobos JA; INER Working Group on Influenza. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009 Aug 13;361(7):680-9. doi: 10.1056/NEJMoa0904252. Epub 2009 Jun 29.

Starting date: December 2013
Last updated: August 5, 2014