H5 Vaccine Alone or With Adjuvant in Healthy Adults

NCT00296634 | Completed Phase 1

• 1 other identifier: 05-0127
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 4

Brief Summary

This randomized, controlled, double-blinded, dose-ranging, Phase I-II study in 600 healthy adults, 18 to 49 years old, is designed to investigate the safety, reactogenicity, and dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine when given alone or combined with aluminum hydroxide. A secondary goal is to guide selection of vaccine dosage levels for expanded Phase II trials based on reactogenicity and immunogenicity profiles. This dose optimization will be applied to both younger and older subject populations in subsequent studies. Subjects who meet the entry criteria for the study will be enrolled at one of 4 study sites and will be randomized into one of 8 groups to receive 2 doses of influenza A/H5N1 vaccine containing 3.75, 7.5, 15, or 45 mcg of HA with or without aluminum hydroxide adjuvant by intramuscular injection. Participants may be involved in study related procedures for up to 8 months.

Conditions

Influenza

Keywords

H5N1, Influenza, vaccine

Outcome Measures

Primary Outcomes (5)

• Adverse event (AE) or serious adverse event (SAE) information (solicited in the clinic and via memory aids, concomitant medications, and periodic targeted physical assessments).

  Adverse events will be collected through 28 days following the second dose of vaccine (approximately Day 56). Serious adverse events will be collected throughout the study through Day 208.

• Proportion of subjects in each group achieving a serum neutralizing antibody titer of greater than or equal to 1:40 against the influenza A/H5N1 virus.

  28 days following second dose of vaccine.

• Proportion of subjects in each dose group achieving a serum Hemagglutination Inhibition (HAI) antibody titer of greater than or equal to 1:40 against the influenza A/H5N1 virus.

  28 days following second dose of vaccine.

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

  28 days following second dose of vaccine.

• 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 second dose of vaccine.

Secondary Outcomes (3)

• 1 month after receipt of each dose, and 7 months after receipt of the first dose of vaccine.

  1 month after receipt of each dose, and 7 months after receipt of the first dose of vaccine.

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

  1 month after receipt of each dose, and 7 months after receipt of the first dose of vaccine.

• Development of serum antibody responses against antigenically drifted variants of H5N1 influenza virus.

  Blood samples for serum assays will be collected at day 0 and at days 28, 56, and 208 after the first immunization.

Study Arms (4)

1

EXPERIMENTAL

45 microgram dose Hemagglutinin (HA), 120 subjects receiving Aluminum hydroxide and 120 not receiving Aluminum hydroxide.

Drug: Aluminum hydroxide; Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed)

2

EXPERIMENTAL

15 microgram dose HA, 60 subjects receiving Aluminum hydroxide and 60 not receiving Aluminum hydroxide.

Drug: Aluminum hydroxide; Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed)

4

EXPERIMENTAL

3.75 microgram dose HA, 60 subjects receiving Aluminum hydroxide and 60 not receiving Aluminum hydroxide.

Drug: Aluminum hydroxide; Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed)

3

EXPERIMENTAL

7.5 microgram dose HA, 60 subjects receiving Aluminum hydroxide and 60 not receiving Aluminum hydroxide.

Drug: Aluminum hydroxide; Biological: Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed)

Interventions

Aluminum hydroxide DRUG

Aluminum hydroxide adjuvant at 1200 mcg/mL.

1; 2; 3; 4

Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur pre-adsorbed) BIOLOGICAL

Inactivated monovalent subvirion influenza H5N1 vaccine produced with and without Aluminum hydroxide adjuvant. All formulations of the H5N1 vaccine are supplied in a unit dose (0.5 mL) vial as a sterile solution for intramuscular injection. Vaccine with adjuvant is a turbid liquid whitish-grey in color. Vaccine without adjuvant is essentially clear and slightly opalescent in color.

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Are males or nonpregnant females between the ages of 18 and 49 years, inclusive.
• Agree to practice adequate contraception (i.e., barrier methods, abstinence, intrauterine devices, and licensed hormonal methods) for the entire study period if they are females of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to 1 year).
• Are in good health as determined by vital signs, medical history to ensure stable medical condition, and targeted physical examination based on medical history.
• Are able to understand and comply with planned study procedures.
• Provide written informed consent prior to initiation of any study procedures.

You may not qualify if:

• Have a known allergy to eggs or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal, aluminum hydroxide, and chicken protein).
• Have a positive urine or serum pregnancy test 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.
• Are receiving psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene, chlorpromazine, perphenazine, trifluopromazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate). Subjects who are receiving a single antidepressant drug and stable for at least 3 months prior to enrollment, without de-compensating symptoms will be allowed to be enrolled in the study.
• 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.

Sponsors & Collaborators

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

Study Sites (4)

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27704, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Keitel WA, Campbell JD, Treanor JJ, Walter EB, Patel SM, He F, Noah DL, Hill H. Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-II randomized clinical trial. J Infect Dis. 2008 Nov 1;198(9):1309-16. doi: 10.1086/592172.

  PMID: 18808338 DERIVED

MeSH Terms

Conditions

Influenza, Human; Influenza in Birds

Interventions

Aluminum Hydroxide

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Bird Diseases; Animal 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: February 23, 2006
• First Posted: February 27, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: August 27, 2010

Record last verified: 2008-09

Locations

US (4)