Clinical trial NCT02008578: Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)
Official title: Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: Antiviral
Adjunctive Therapy
Antibody
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2013-12-11
Enrollment: 31
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: 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.

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.

Eligibility 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)

Primary outcomes:
measure: Hemagglutination Inhibition (HAI) titer for each influenza strain (H1N1, H3N2, B) taken 1 hour postinfusion compared to predicted levels.
timeFrame: 1 hour
Secondary outcomes:
measure: 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
timeFrame: Measured through Day 7
Other outcomes:
measure: Length of hospital stay (for hospitalized participants)
timeFrame: Measured through the participant's hospital stay
measure: Self-reported functional status and symptoms on Days 3 and 7
timeFrame: Measured through Day 7
measure: Adverse effects of the study treatment
timeFrame: Measured through Day 28
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
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: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892
name: Richard Davey, MD
role: STUDY_CHAIR
affiliation: The Henry Ford Hospital, Detroit, MI 48202
name: Norman Markowitz, MD
role: STUDY_CHAIR
References:
citation: 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(0 2):B56-62. doi: 10.1016/j.vaccine.2011.04.105.
citation: 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. doi: 10.7326/0003-4819-145-8-200610170-00139. Epub 2006 Aug 29.
citation: Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-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.
citation: INSIGHT FLU005 IVIG Pilot Study Group. INSIGHT FLU005: An Anti-Influenza Virus Hyperimmune Intravenous Immunoglobulin Pilot Study. J Infect Dis. 2016 Feb 15;213(4):574-8. doi: 10.1093/infdis/jiv453. Epub 2015 Sep 15.