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

December 14, 2019 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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....

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

    1. Age greater than or equal to 18 years and less than or equal to 50 years
    2. Weight less than or equal to 100 kg
    3. 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
    4. 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:

  1. 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
  2. Women who are breast-feeding
  3. Positive urine or serum pregnancy test
  4. Known sensitivity to IVIG
  5. IgA < 7 mg/dL
  6. Influenza HAI H1N1 > 1:20
  7. Receipt of any vaccination within 30 days prior to study drug administration
  8. Pre-existing condition that is associated with an increased risk of thrombosis such as cryoglobulinemia, hyper-triglyceridemia, or monoclonal gammopathies
  9. Estimated glomerular filtration rate (GFR) < 60 mL/min at screening, calculated using the MDRD formula
  10. Medical conditions for which receipt of up to 750 mL volume may be dangerous to the patient (e.g., decompensated congestive heart failure)

  11. 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

  12. 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

  13. Positive serology for Hepatitis B surface antigen
  14. Positive serology for Hepatitis C
  15. Positive serology for HIV-1
  16. 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)
  17. 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
  18. 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
  19. Patients who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 3, 2014

Primary Completion (Actual)

December 2, 2014

Study Completion (Actual)

December 2, 2014

Study Registration Dates

First Submitted

January 14, 2014

First Submitted That Met QC Criteria

January 14, 2014

First Posted (Estimate)

January 15, 2014

Study Record Updates

Last Update Posted (Actual)

December 17, 2019

Last Update Submitted That Met QC Criteria

December 14, 2019

Last Verified

December 2, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 140043
  • 14-I-0043

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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