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

NCT02037282 | Withdrawn Phase 1

• 2 other identifiers: 14004314-I-0043
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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....

Conditions

Influenza; Flu

Keywords

HAI Titer; Hemagglutination Inhibition Assays; Immunogenicity; Serum Antibody Response

Outcome Measures

Primary Outcomes (1)

• HAI titer levels predose, at 1 hr post-infusion, and on Days 3, 7, 14 and 28

  6 months

Secondary Outcomes (1)

• Type and frequency of adverse events experienced by subjects receiving anti-influenza IVIG by intravenous administration at escalating dose-levels

  6 months

Interventions

Anti-influenza IVIG DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

Sponsors & Collaborators

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

Related Publications (3)

• Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon AF, Lapinsky S, Ahern SP, Smith O, Siddiqui F, Jouvet P, Khwaja K, McIntyre L, Menon K, Hutchison J, Hornstein D, Joffe A, Lauzier F, Singh J, Karachi T, Wiebe K, Olafson K, Ramsey C, Sharma S, Dodek P, Meade M, Hall R, Fowler RA; Canadian Critical Care Trials Group H1N1 Collaborative. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA. 2009 Nov 4;302(17):1872-9. doi: 10.1001/jama.2009.1496. Epub 2009 Oct 12.

  PMID: 19822627 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

• 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

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 T Davey, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 15, 2014
• Study Start: January 3, 2014
• Primary Completion: December 2, 2014
• Study Completion: December 2, 2014
• Last Updated: December 17, 2019

Record last verified: 2014-12-02