A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of a Recombinant Vaccinia-HIV-1 IIIB Env/Gag/Pol Vaccine (TBC-3B)

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000767

Collaborator

(none)

Enrollment

Locations

3.6

Patients Per Site

Study Details

Study Description

Brief Summary

To evaluate, in healthy HIV-1 seronegative vaccinia-immune and vaccinia-naive volunteers, the safety and immunogenicity of an HIV-1 candidate vaccine (TBC-3B) consisting of a live recombinant vaccinia virus expressing the env, gag, and pol genes of HIV-1 IIIB strain. To evaluate the potential of boosting with one of a variety of HIV-1 recombinant subunit, peptide, or pseudovirion vaccines, if available, to augment the immune responses of the vaccinees.

Antigenic drift, defined as the genetic variation of the HIV-1 envelope gene that results in antigenic variation during natural infection, may confound attempts to achieve protective immunity using a vaccine based solely on HIV-1 envelope proteins. Inclusion of conserved core and polymerase proteins along with envelope protein in a candidate vaccine may address some of the problems with antigenic variability. A prime-boost immunization approach using a novel priming immunogen expressing env, gag, and pol genes of the HIV-1 IIIB strain will be attempted in this study.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: TBC-3B Vaccine Biological: Smallpox Vaccine	Phase 1

Detailed Description

In Part I, vaccinia-immune volunteers are randomized to one of two regimens. Group A receives priming with TBC-3B on days 0 and 56, followed by boosting on day 224 (8 months) with one of the following: TBC-3B, an alternative immunogen such as pseudovirion particles or a recombinant HIV-1 subunit or peptide vaccine, or placebo. Group B receives priming with control vaccine (DryVax), followed by boosting with an appropriate placebo. At least 50 percent of subjects in Part I will be observed for a minimum of 8 weeks before subsequent volunteers are enrolled in Part II. PER 11/18/94 AMENDMENT, Part I boosting is given on day 392. PER 5/19/95 AMENDMENT, Part I boosting is given on day 756 if not available on day 392; if the appropriate product is not available then, the study will end on day 756. In Part II, vaccinia-naive volunteers are randomized to one of three regimens. Group C receives TBC-3B on day 0 and saline placebo on day 56. Group D receives TBC-3B on days 0 and 56. Both Group C and D receive boosting with TBC-3B or an alternative immunogen on day 224. Group E receives control vaccine (DryVax) on days 0 and 56, followed by appropriate placebo on day 224. Per 06/10/94 addendum, volunteers will be contacted once or twice per year for at least 5 years to check on health status.

NOTE: Part I (Part A) of the protocol has closed to accrual.

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Prevention

Official Title:

A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of a Recombinant Vaccinia-HIV-1 IIIB Env/Gag/Pol Vaccine (TBC-3B)

Actual Study Completion Date :

Jul 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

Subjects must have:

Negative ELISA and Western blot for HIV-1 within 6 weeks prior to immunization.
Normal history and physical exam.
History of smallpox vaccination at least 5 years prior to study entry (Part I) OR no prior smallpox vaccination (Part II).
Absolute CD4 count >= 400 cells/mm3.
Normal urinalysis.

NOTE:

No more than 10 percent of volunteers in both Parts I and II may be over 50 years of age.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

Positive hepatitis B surface antigen.
Medical or psychiatric condition (such as recent suicidal ideation or present psychosis) that precludes compliance.
Occupational responsibilities that preclude compliance.
Active syphilis. NOTE: Subjects with serology documented to be a false positive or due to a remote (> 6 months) treated infection are eligible.
Active tuberculosis. NOTE: Subjects with a positive PPD and a normal chest x-ray showing no evidence of TB and not requiring isoniazid therapy are eligible.
Eczema.
Household contact with persons meeting any of the following criteria:
pregnancy, less than 12 months of age, eczema, immunodeficiency disease, or use of immunosuppressive medications.

Subjects with the following prior conditions are excluded:

History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications.
History of anaphylaxis or other serious adverse reactions to vaccines.
Eczema within the past year.
History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Steven-Johnson syndrome, bronchospasm, or hypotension).
Prior psychiatric condition (such as history of suicide attempts or past psychosis) that precludes compliance.
History of cancer unless there has been surgical excision that is considered to have achieved cure.

Prior Medication:

Excluded:

Prior HIV vaccines.
Live attenuated vaccines within the past 60 days. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) do not exclude but should be administered at least 2 weeks prior to HIV immunizations.
Experimental agents within the past 30 days.

Prior Treatment:

Excluded:

Receipt of blood products or immunoglobulins within the past 6 months. It is STRONGLY RECOMMENDED that any activity that might expose subject to HIV (unprotected sex or needle sharing) be avoided.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Louis Univ. School of Medicine AVEG	Saint Louis	Missouri	United States	63104
2	Univ. of Rochester AVEG	Rochester	New York	United States	14642
3	JHU AVEG	Pittsburgh	Pennsylvania	United States
4	Vanderbilt Univ. Hosp. AVEG	Nashville	Tennessee	United States	37232
5	UW - Seattle AVEG	Seattle	Washington	United States	98144