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

Study Overview
=================
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.

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

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Intravenous hyperimmune immunoglobulin (Flu-IVIG)
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous hyperimmune immunoglobulin (Flu-IVIG)<br>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)<br> <br> |
| Placebo Comparator: Placebo<br>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<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination Inhibition (HAI) titer for each influenza strain (H1N1, H3N2, B) taken 1 hour postinfusion compared to predicted levels. |  | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | assessment of influenza viral replication by Day 3; preliminary assessment of possible antiviral efficacy | Measured through Day 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Antiviral, Adjunctive Therapy, Antibody