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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.
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000866
  Purpose

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 Intervention
HIV Infections
Biological: MN rgp120/HIV-1
Biological: TBC-3B Vaccine

MedlinePlus related topics: AIDS
Drug Information available for: PANVAC-V Alum, potassium Aluminum sulfate
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Double-Blind, Safety Study
Official Title: 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.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 36
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

Patients must have:

  • Negative FDA-approved ELISA for HIV within 8 weeks of immunization.
  • Normal history and physical examination.
  • Negativity for Hepatitis B surface antigen.
  • 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:

  • 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.
  • 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.
  • 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.
  • 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:

  • History of immunodeficiency, chronic illness, malignancy or autoimmune disease.
  • History of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
  • Any history of anaphylaxis or history of other serious adverse reactions to vaccines.
  • History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
  • Eczema within the past year.
  • History of smallpox vaccination.
  • Envelope bands on HIV-1 Western blot within 8 weeks of immunization.

Prior Medication: Excluded:

  • Use of immunosuppressive.
  • Live attenuated vaccines within 60 days of study.
  • 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.
  • Experimental agents within 30 days prior to study.
  • 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:

  • History of injection drug use within the last 12 months prior to enrollment.
  • Higher or intermediate risk sexual behavior as defined by the AVEG.
  • Lower risk sexual behavior as defined by AIDS Vaccine Evaluation Group (AVEG) procedures.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000866

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Maryland
Johns Hopkins Univ / School of Hygiene & Public Health
Baltimore, Maryland, United States, 212051901
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States, 21205
United States, Missouri
St Louis Univ School of Medicine
St. Louis, Missouri, United States, 63104
Saint Louis Univ Health Sciences Ctr
Saint Louis, Missouri, United States, 63110
United States, New York
Univ of Rochester Med Ctr
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt Univ Hosp
Nashville, Tennessee, United States, 37232
United States, Washington
Univ of Washington / Pacific Med Ctr
Seattle, Washington, United States, 98144
Sponsors and Collaborators
Investigators
Study Chair: Smith C
  More Information

Publications:
Keefer MC, McElrath MJ, Weinhold K, Gorse GJ, Mulligan M, Francis D, Panicali D. A phase I trial of vaccina-eng/gag/pol (TBC-3B) given by alternative routes, boosted with rgp120. Int Conf AIDS. 1998;12:278 (abstract no 496/21199)

Study ID Numbers: AVEG 014C
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000866  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
Vaccinia Virus
Placebos
HIV-1
AIDS Vaccines
HIV Seronegativity
Genes, env
Genes, pol
Genes, gag
HIV Preventive Vaccine

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Aluminum sulfate
Poxviridae Infections
Vaccinia
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
DNA Virus Infections
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 15, 2009