Dose-Escalating Trial Using Vero Cell-culture Derived H5N1 +/- Aluminum in Adults

NCT00382980 | Completed Phase 1

• 1 other identifier: 06-0052
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this research study is to compare how the body reacts to different strengths of an experimental cell culture-grown whole virus A/H5N1 flu vaccine when given with or without the addition of aluminum hydroxide adjuvant. Researchers will also look at how much antibody is made to the influenza virus hemagglutinin (HA) after subjects receive the H5N1 vaccine. Three hundred healthy adults aged 18-40 years will participate for approximately 9 months, which includes screening. Participants will receive 2 doses of vaccine or placebo injected 28 days apart. Participants will have blood samples taken up to 7 times and have 8 scheduled study visits.

Conditions

Influenza

Keywords

influenza, vaccine, A/H5N1, aluminum hydroxide, Vero cell

Outcome Measures

Primary Outcomes (5)

• Adverse event (AE) or serious adverse event (SAE) information (solicited in the clinic and via memory aids, concomitant medications, periodic targeted physical assessment, and laboratory safety evaluations for a subset of subjects.

  Duration of study.

• Proportion of subjects in each dose group achieving a serum neutralizing antibody titer of greater than or equal to 40 against the influenza A/H5N1 virus.

  28 days after receipt of the 2nd dose of vaccine, approximately Day 56.

• Proportion of subjects in each dose group achieving a serum hemagglutination inhibition (HAI) antibody titer of greater than or equal to 40 against the influenza A/H5N1 virus.

  28 days after receipt of the 2nd dose of vaccine, approximately Day 56.

• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers in each group.

  28 days after receipt of the 2nd dose of vaccine, approximately Day 56.

• Geometric mean titer (GMT) and frequency of 4-fold or greater increases in serum HAI antibody titers in each group.

  28 days after receipt of the 2nd dose of vaccine, approximately Day 56.

Secondary Outcomes (2)

• GMT and frequency of 4-fold or greater increases in neutralizing antibody titers in each group.

  1 month and 7 months after receipt of the 1st dose of vaccine.

• GMT and frequency of 4-fold or greater increases in serum HAI antibody titers in each group.

  1 month and 7 months after receipt of the 1st dose of vaccine.

Study Arms (6)

7.5-

EXPERIMENTAL

7.5 mcg of vaccine without adjuvant administered on Days 0 and 28.

Biological: Inactivated Vero cell based whole virus influenza A/H5N1

45-

EXPERIMENTAL

45 mcg of vaccine without adjuvant administered on Days 0 and 28.

Biological: Inactivated Vero cell based whole virus influenza A/H5N1

Placebo

PLACEBO COMPARATOR

Placebo administered on Days 0 and 28.

Drug: Placebo

15+

EXPERIMENTAL

15 mcg of vaccine with aluminum hydroxide adjuvant administered on Days 0 and 28.

Biological: Aluminum hydroxide; Biological: Inactivated Vero cell based whole virus influenza A/H5N1

7.5+

EXPERIMENTAL

7.5 mcg of vaccine with aluminum hydroxide adjuvant administered on Days 0 and 28.

Biological: Aluminum hydroxide; Biological: Inactivated Vero cell based whole virus influenza A/H5N1

15-

EXPERIMENTAL

15 mcg of vaccine without adjuvant administered on Days 0 and 28.

Biological: Inactivated Vero cell based whole virus influenza A/H5N1

Interventions

Aluminum hydroxide BIOLOGICAL

Adjuvant administered with A/H5N1 vaccine dosages 7.5 mcg and 15 mcg.

15+; 7.5+

Inactivated Vero cell based whole virus influenza A/H5N1 BIOLOGICAL

Inactivated Vero cell-grown, whole virus, influenza A/H5N1 vaccine at dosages 7.5 mcg and 15 mcg of hemagglutinin (HA) per 0.5 mL, each dosage with and without aluminum hydroxide adjuvant; 45 mcg HA/0.5 mL without adjuvant.

15+; 15-; 45-; 7.5+; 7.5-

Placebo DRUG

Saline injected into the deltoid muscle. 2 identical dosages will be given approximately 28 days apart.

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Stage 1 Cohort
• Healthy males and females aged 18 to 40 years, inclusive;
• Females of childbearing potential must agree to practice adequate contraception for the duration of the study (not surgically sterile or Aftermenopausal for at least 1 year);
• Good health as determined by screening medical history and physical examination;
• On no medications with the exception of licensed hormonal contraceptives and vitamins;
• Willingness to comply with study procedures;
• Ability to provide informed consent;
• Availability for follow-up for 6 months after second vaccination;
• Normal screening laboratory values for total WBC, platelet count, hemoglobin, creatinine, and alanine aminotransferase (Stage 1 only).
• Stage 2 Cohort
• Healthy males and non-pregnant females aged 18 to 40 years, inclusive.
• Females of childbearing potential must agree to practice adequate contraception for the duration of the study.
• Good health as determined by screening medical history and physical examination.
• Willingness to comply with study procedures.
• Ability to provide informed consent.

You may not qualify if:

• Stage 1 Cohort
• Have a positive urine or serum pregnancy test in the 24 hours prior to vaccination (if female of childbearing potential) or are women who are breastfeeding.
• Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.
• Have an active neoplastic disease or a history of any hematologic malignancy.
• Have long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed.)
• Have a diagnosis of schizophrenia, Bi-polar disease or other major psychiatric diagnosis.
• Have been hospitalized for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
• Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
• Have received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to vaccination in this study.
• Have an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses (This includes, but is not limited to, known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients.)
• Have a history of severe reactions following immunization with contemporary influenza virus vaccines.
• Have an acute illness, including an oral temperature greater than 100.4 degrees F, within 1 week of vaccination.
• Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during the 7-month study period.
• Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render them unable to meet the requirements of the protocol.
• Participated in an influenza A/H5 vaccine study in the past in a group receiving vaccine (but does not exclude documented placebo recipients).

Sponsors & Collaborators

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

Study Sites (5)

Stanford University

Stanford, California, 94305, United States

Location

UCLA Center For Vaccine Research

Torrance, California, 90502, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Keitel WA, Dekker CL, Mink C, Campbell JD, Edwards KM, Patel SM, Ho DY, Talbot HK, Guo K, Noah DL, Hill H. Safety and immunogenicity of inactivated, Vero cell culture-derived whole virus influenza A/H5N1 vaccine given alone or with aluminum hydroxide adjuvant in healthy adults. Vaccine. 2009 Nov 5;27(47):6642-8. doi: 10.1016/j.vaccine.2009.03.015. Epub 2009 Mar 25.

  PMID: 19773098 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Aluminum Hydroxide

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 28, 2006
• First Posted: October 2, 2006
• Study Start: October 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: August 27, 2010

Record last verified: 2008-09

Locations

US (5)