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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Influenza

Treatments: Biological: Placebo; Biological: Intravenous hyperimmune immunoglobulin (Flu-IVIG)

Study type: Interventional

Funder types: NIH

Identifiers

NCT02008578

14-I-0031

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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31 participants in 2 patient groups, including a placebo group

Intravenous hyperimmune immunoglobulin (Flu-IVIG)

Experimental group

Description:

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.

Treatment:

Biological: Intravenous hyperimmune immunoglobulin (Flu-IVIG)

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Biological: Placebo