Clinical trial NCT00000866: 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.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Vaccines, Synthetic
Vaccinia Virus
Placebos
HIV-1
AIDS Vaccines
HIV Seronegativity
Genes, env
Genes, pol
Genes, gag
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Primary purpose: PREVENTION

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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: JHU AVEG
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis Univ. School of Medicine AVEG
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt Univ. Hosp. AVEG
state: Tennessee
city: Seattle
country: United States
facility: UW - Seattle AVEG
state: Washington
Study officials:
name: Smith C
role: STUDY_CHAIR
References:
citation: 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)