Development of Immune Globulin Treatment for Avian Flu

NCT00383071 | Terminated Phase 2 Results DMC

• 2 other identifiers: 06-I-0235060235
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine how best to use a vaccine for generating high levels of antibodies called immune globulins (IVIG) in people, which, in turn, can be collected and used to develop a possible treatment for avian influenza (bird flu). Immune globulins are proteins made by the body that attack the influenza virus. This study will use an experimental bird flu vaccine to stimulate immune globulin production in healthy people. The vaccine is similar to the regular influenza vaccine and has been studied in more than 450 people. This study will use high doses of the vaccine to generate high antibody levels that can be collected for producing the new treatment. Healthy adults between 18 and 60 years of age who weigh at least 110 pounds may be eligible for this study. Candidates are screened with a medical history and physical examination. Participants are given one of three doses of the vaccine, depending on when they enter the study. The first 25 people enrolled receive a dose of 90 micrograms (mcg). If this dose is well tolerated, the next 25 people receive 120 mcg, and if this dose is also well tolerated, the last 25 people receive 180 mcg. Vaccination consists of either two shots (one in the muscle of each arm) or one shot in the buttock on four occasions. Subjects are vaccinated on four occasions, each 4 weeks apart. On the day of each vaccination, subjects provide a blood sample to evaluate blood counts, chemistries, and antibody levels, and to test for HIV, hepatitis B and C, syphilis, and antibody against avian flu. For 7 days after each vaccination, subjects keep a diary card to record any symptoms, such as pain, fever, muscle aches, or others. At the end of the 7 days, they are contacted by study staff to report the symptoms. In addition to the vaccinations, subjects undergo apheresis to collect IVIG once their blood test shows moderately high antibody levels. For this procedure, blood is collected through a needle in an arm vein and flows through a catheter (plastic tube) into a machine that separates the blood cells from the antibodies and protein. The antibodies and protein are collected and the rest of the blood is returned to the body. Subjects are asked to undergo at least three apheresis procedures. ...

Conditions

Infectious Diseases; Influenza; Avian Flu

Keywords

Apheresis; Avian Flu; Healthy Volunteers; Infectious Diseases; IVIG; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Safety of H5N1 Vaccine as Measured by Adverse Events

  The number of subjects experiencing adverse events after receiving H5N1 vaccine

  Day 28, 56, 84

Study Arms (4)

Cohort 1

ACTIVE COMPARATOR

H5N1 vaccine - 90 mcg IM every 4 week x 4 doses Apheresis - if HAI titer above 1:160

Biological: H5N1 vaccine; Procedure: Apheresis

Cohort 2

ACTIVE COMPARATOR

H5N1 vaccine - 120 mcg IM every 4 week x 4 doses Apheresis - if HAI titer above 1:160

Biological: H5N1 vaccine; Procedure: Apheresis

Cohort 3

ACTIVE COMPARATOR

H5N1 vaccine - 180 mcg IM every 4 week x 4 doses Apheresis - if HAI titer above 1:160

Biological: H5N1 vaccine; Procedure: Apheresis

Cohort 4

ACTIVE COMPARATOR

H5N1 vaccine - 180 mcg IM every 4 weeks x 2 doses, injection site randomized to either deltoid or gluteus Apheresis - if HAI titer above 1:160

Biological: H5N1 vaccine; Procedure: Apheresis

Interventions

H5N1 vaccine BIOLOGICAL

Monovalent subvirion H5N1 vaccine (rgA/Vietnam/1203/2004) 90 mcg/mL Manufactured by Sanofi Pasteur Inc, Swiftwater, PA.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Apheresis PROCEDURE

Once subjects achieved a high antibody titer (\>1:160), they could begin apheresis to collect plasma.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥ 18 years old, and \< 60 years old.
• Adequate clinical parameters (all of the following):
• Afebrile (temperature \< 38° C)
• Systolic blood pressure \>100 \& \<180 mmHg
• Diastolic blood pressure \>50 \& \<100 mmHg
• Heart rate between 40-100 beats/minute
• Weight ≥ 110 pounds (50kg)
• Adequate peripheral venous access for plasmapheresis (as judged by the examiner)
• Females of child-bearing potential must (one of the following):
• Be surgically sterile.
• Be abstinent (or willing to be) 4 weeks prior to date of screening evaluation through the last apheresis session (estimate 6 months).
• Use oral contraceptives, or other form of hormonal birth control including hormonal vaginal rings or transdermal patches, and have been using these for 3 months prior to date of screening evaluation through the last apheresis session (estimate 6 months).
• Use an intra-uterine device (IUD) as birth control 4 weeks prior to date of screening evaluation through the last apheresis session (estimate 6 months).
• Use (by ensuring her male partner(s) uses) barrier contraception (condom) with a spermicide as birth control 4 weeks prior to date of screening evaluation through the last apheresis session (estimate 6 months).

You may not qualify if:

• Has a medical history of
• Thrombocytopenia or other blood dyscrasias
• congestive heart failure
• pulmonary hypertension
• bleeding diathesis or therapeutic anticoagulation
• HIV/AIDS
• Hepatitis B
• Hepatitis C
• Known history of hepatitis after the 11th birthday.
• Trypanosomiasis (Chagas' disease and sleeping sickness)
• Leishmaniasis (Kala-azar)
• Filariasis
• Q fever
• Yaws
• Allergy to eggs, thimerosal, or other components of the vaccine

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Morse SS. Factors in the emergence of infectious diseases. Emerg Infect Dis. 1995 Jan-Mar;1(1):7-15. doi: 10.3201/eid0101.950102.

  PMID: 8903148 BACKGROUND

• de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005 Dec 22;353(25):2667-72. doi: 10.1056/NEJMoa054512.

  PMID: 16371632 BACKGROUND

• Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, Lochindarat S, Srisan P, Suwan P, Osotthanakorn Y, Anantasetagoon T, Kanjanawasri S, Tanupattarachai S, Weerakul J, Chaiwirattana R, Maneerattanaporn M, Poolsavathitikool R, Chokephaibulkit K, Apisarnthanarak A, Dowell SF. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis. 2005 Feb;11(2):201-9. doi: 10.3201/eid1102.041061.

  PMID: 15752436 BACKGROUND

• Lu H, Khurana S, Verma N, Manischewitz J, King L, Beigel JH, Golding H. A rapid Flp-In system for expression of secreted H5N1 influenza hemagglutinin vaccine immunogen in mammalian cells. PLoS One. 2011 Feb 28;6(2):e17297. doi: 10.1371/journal.pone.0017297.

  PMID: 21386997 DERIVED

• Beigel JH, Voell J, Huang CY, Burbelo PD, Lane HC. Safety and immunogenicity of multiple and higher doses of an inactivated influenza A/H5N1 vaccine. J Infect Dis. 2009 Aug 15;200(4):501-9. doi: 10.1086/599992.

  PMID: 19569973 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Communicable Diseases; Influenza, Human; Influenza in Birds

Interventions

Blood Component Removal

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Bird Diseases; Animal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: John Beigel, M.D.
• Organization: SAIC/National Institute of Allergy and Infectious Diseases

jbeigel@niaid.nih.gov

+1 301 451 9881

Study Officials

• H. Clifford Lane, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2006
• First Posted: October 2, 2006
• Study Start: August 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: December 1, 2014
• Last Updated: July 31, 2018
• Results First Posted: May 27, 2013

Record last verified: 2016-04

Locations

US (1)