A Phase 1, Open Label, Ascending Dose Cohort Study of the Pharmacokinetics of Anti-Influenza Hyperimmune Intravenous Immunoglobulin in Healthy Subjects

Study Overview
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Brief Summary
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Despite currently available antivirals, influenza causes significant morbidity and mortality, with 226,000 excess hospitalizations and 30,000-50,000 deaths each year in the United States alone, and more therapies are needed in the armamentarium of anti-influenza medications including humoral immunity-based agents. This study will evaluate the pharmacokinetics of an anti-influenza hyperimmune intravenous immunoglobulin. Beginning with a low dose, subjects will receive anti-influenza intravenous immunoglobulin (FLU-IVIG) and evaluated on Study Days 0, 3, 7, 14, and 28. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, and pharmacokinetics. Utilizing serum antibody responses as determined by hemagglutination inhibition (HAI) assays, the dose will be escalated as immunogenicity is established....

Detailed Description
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Despite currently available antivirals, influenza causes significant morbidity and mortality, with 226,000 excess hospitalizations and 30,000-50,000 deaths each year in the United States alone, and more therapies are needed in the armamentarium of anti-influenza medications including humoral immunity-based agents. This study will evaluate the pharmacokinetics of an anti-influenza hyperimmune intravenous immunoglobulin. Beginning with a low dose, subjects will receive anti-influenza intravenous immunoglobulin (FLU-IVIG) and evaluated on Study Days 0, 3, 7, 14, and 28. The safety and tolerability is evaluated using symptoms, clinical laboratory tests, and pharmacokinetics. Utilizing serum antibody responses as determined by hemagglutination inhibition (HAI) assays, the dose will be escalated as immunogenicity is established.

Official Title
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A Phase 1, Open Label, Ascending Dose Cohort Study of the Pharmacokinetics of Anti-Influenza Hyperimmune Intravenous Immunoglobulin in Healthy Subjects

Conditions
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Influenza, Flu

Intervention / Treatment
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* Drug: Anti-influenza IVIG


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Age greater than or equal to 18 years and less than or equal to 50 years Weight less than or equal to 100 kg Patients must be willing to forgo the seasonal influenza vaccine for 28 days, and the MMR and varicella vaccines for 3 months post infusion of the study drug Females who are able to become pregnant (i.e., are not postmenopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 1 effective form of contraception from the date of the subject s signing of the informed consent form through 28 days after the dose of the study drug EXCLUSION CRIATERIA: Any chronic medical problem that requires daily oral medications (except Tylenol, oral contraceptives, vitamins, and seasonal allergy medications), or other medical history that in the opinion of the investigator significantly increases the risk associated with IVIG Women who are breast-feeding Positive urine or serum pregnancy test Known sensitivity to IVIG IgA < 7 mg/dL Influenza HAI H1N1 > 1:20 Receipt of any vaccination within 30 days prior to study drug administration Pre-existing condition that is associated with an increased risk of thrombosis such as cryoglobulinemia, hyper-triglyceridemia, or monoclonal gammopathies Estimated glomerular filtration rate (GFR) < 60 mL/min at screening, calculated using the MDRD formula Medical conditions for which receipt of up to 750 mL volume may be dangerous to the patient (e.g., decompensated congestive heart failure) Abnormal chemistry panel -Defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table --Evaluating only total CO2 (bicarbonate), creatinine, alkaline phosphatase, ALT, AST, total bilirubin, and estimated GFR by the MDRD equation Abnormal complete blood count (CBC) -Defined as any clinically significant baseline Grade 1 or greater toxicity, or any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table --Evaluating only the WBC, hemoglobin, hematocrit, and platelets Positive serology for Hepatitis B surface antigen Positive serology for Hepatitis C Positive serology for HIV-1 Prior treatment with any investigational drug therapy within 5 half-lives or 30 days, whichever is longer, prior to study drug administration (i.e., Day 0) Receipt of blood products from 30 days prior to study drug administration (i.e., Day 0) through 28 days after the dose of the study drug Presence of any pre-existing illness that, in the opinion of the investigator, would place the patient 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Anti-influenza IVIG|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI titer levels predose, at 1 hr post-infusion, and on Days 3, 7, 14 and 28 |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type and frequency of adverse events experienced by subjects receiving anti-influenza IVIG by intravenous administration at escalating dose-levels |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAI Titer, Hemagglutination Inhibition Assays, Immunogenicity, Serum Antibody Response