A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of the Therion Recombinant Vaccinia-HIV-1 IIIB ENV/GAG/POL Vaccine (TCB-3B) and MN RGP 120/HIV-1 In Alum.
Study Details
Study Description
Brief Summary
To evaluate the safety of administering Therion Recombinant Vaccinia-HIV-1 IIIB env/gag/pol Vaccine (TBC-3B) vaccinations to vaccinia-naive individuals. To evaluate the immunogenicity of priming with TBC-3B by the scarification, intradermal, and subcutaneous routes, followed by booster immunization of MN rgp120 HIV-1. To compare the immunogenicity of priming with TBC-3B in vaccinia-naive individuals to vaccinia-immune individuals.
In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed Description
In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.
After volunteers are recruited, screened and enrolled in the study, they will be randomized to group C, D, or E. Each group will enroll 10 patients and 2 controls. The placebo control for TBC-3B will be standard vaccinia vaccination administered at doses no higher than that administered by scarification; the placebo control for MN rgp120 will be alum. Group C will receive undiluted TBC-3B by scarification, at months 0 and 2. Group D will receive diluted TBC-3B intradermally at month 0 and undiluted TBC-3B at month 2. Group E will receive diluted TBC-3B subcutaneously at month 0 and undiluted TBC-3B at month 2. At months 8 and 12 all groups will receive MN rgp 120/HIV-1 in alum intramuscularly.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria
Patients must have:
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Negative FDA-approved ELISA for HIV within 8 weeks of immunization.
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Normal history and physical examination.
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Negativity for Hepatitis B surface antigen.
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Availability for follow-up for planned duration of the study (18 months).
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
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Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. Specifically excluded are people with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis.
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Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (> 6 months) treated infection, the volunteer is eligible.
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Active tuberculosis. NOTE: Patients with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring INH therapy are eligible.
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Household contacts with, or occupational exposure to, people with any of the following:
Pregnancy. <12 months of age. Eczema or Immunodeficiency disease. Use of immunosuppressive medications.
Patients with the following prior conditions are excluded:
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History of immunodeficiency, chronic illness, malignancy or autoimmune disease.
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History of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
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Any history of anaphylaxis or history of other serious adverse reactions to vaccines.
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History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
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Eczema within the past year.
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History of smallpox vaccination.
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Envelope bands on HIV-1 Western blot within 8 weeks of immunization.
Prior Medication: Excluded:
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Use of immunosuppressive.
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Live attenuated vaccines within 60 days of study.
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NOTE: Medically indicated subunit or killed vaccines (e.g. influenza, pneumococcal) do not exclude, but should be given at least 2 weeks prior to HIV immunizations.
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Experimental agents within 30 days prior to study.
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Prior receipt of HIV-1 vaccines or placebo recipient in a previous HIV vaccine trial.
Receipt of blood products or immunoglobulin within past 6 months.
Risk Behavior: Excluded:
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History of injection drug use within the last 12 months prior to enrollment.
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Higher or intermediate risk sexual behavior as defined by the AVEG.
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Lower risk sexual behavior as defined by AIDS Vaccine Evaluation Group (AVEG) procedures.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | JHU AVEG | Baltimore | Maryland | United States | |
2 | St. Louis Univ. School of Medicine AVEG | Saint Louis | Missouri | United States | |
3 | Vanderbilt Univ. Hosp. AVEG | Nashville | Tennessee | United States | 37232 |
4 | UW - Seattle AVEG | Seattle | Washington | United States | 98144 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Smith C,
Study Documents (Full-Text)
None provided.More Information
Publications
- AVEG 014C
- 10562