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

NCT02008578 | Completed Phase 1 DMC

• 1 other identifier: 14-I-0031
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 11

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.

Conditions

Influenza

Keywords

Antiviral; Adjunctive Therapy; Antibody

Outcome Measures

Primary Outcomes (1)

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

  1 hour

Secondary Outcomes (1)

• 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

  Measured through Day 7

Other Outcomes (3)

• Length of hospital stay (for hospitalized participants)

  Measured through the participant's hospital stay

• Self-reported functional status and symptoms on Days 3 and 7

  Measured through Day 7

• Adverse effects of the study treatment

  Measured through Day 28

Study Arms (2)

Intravenous hyperimmune immunoglobulin (Flu-IVIG)

EXPERIMENTAL

Adults with confirmed Influenza A or B and evidence of ongoing viral replication (as demonstrated by positive rapid Ag or PCR preferably within 24 hours and no later than 6 days from symptom onset) will receive 0.25g Flu-IVIG/kg of actual body weight, to a maximum dose of 25g Flu-IVIG.

Biological: Intravenous hyperimmune immunoglobulin (Flu-IVIG)

Placebo

PLACEBO COMPARATOR

Adults with Influenza A or B and evidence of ongoing viral replication (as demonstrated by positive rapid Ag or PCR preferably within 24 hours and no later than 6 days from symptom onset) will receive placebo for Flu-IVIG (a comparable volume of saline).

Biological: Placebo

Interventions

Intravenous hyperimmune immunoglobulin (Flu-IVIG) BIOLOGICAL

Intravenous hyperimmune immunoglobulin (Flu-IVIG)

Placebo BIOLOGICAL

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age greater than or equal to 18 years of age
• 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
• 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
• 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
• Willingness to have blood and respiratory samples obtained and stored

You may not qualify if:

• If hospitalized, admitted for reasons other than influenza or complications of influenza
• 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 investigator)
• Known IgA deficiency
• 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)
• 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)
• 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
• Patients who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol
• Medical conditions for which receipt of 500mL volume may be dangerous to the patient (e.g., decompensated congestive heart failure)
• Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (11)

University of California at San Diego

San Diego, California, 92103, United States

Location

Denver Public Health

Denver, Colorado, 80204, United States

Location

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Related Publications (4)

• 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.

  PMID: 21757105 BACKGROUND

• 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.

  PMID: 16940336 BACKGROUND

• 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.

  PMID: 19564631 BACKGROUND

• 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.

  PMID: 26374911 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Richard Davey, MD

  National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892

  STUDY CHAIR

• Norman Markowitz, MD

  The Henry Ford Hospital, Detroit, MI 48202

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 11, 2013
• Study Start: December 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: August 15, 2016

Record last verified: 2016-08

Locations

US (11)