A Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP300 and HIV-1 SF-2 rgp120 in HIV-1 Uninfected Adult Volunteers

HIV Infections Clinical Trial

Official title:

A Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP300 and HIV-1 SF-2 rgp120 in HIV-1 Uninfected Adult Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001072
• Other study ID #: AVEG 026
• Secondary ID: 10576
• Status: Completed
• Phase: Phase 1
• Est. completion date: January 1999

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate, in HIV-negative volunteers, the safety and immunogenicity of ALVAC-HIV MN120TMGNP (vCP300) followed by or combined with boosting using rgp120/HIV-1SF2. To compare ALVAC-HIV vCP300 with ALVAC-RG rabies glycoprotein (vCP65) as a control. To evaluate an accelerated immunization schedule at 0, 1, 3, and 6 months versus 0, 1, 6, and 9 months.

The combination of a live recombinant primer followed by a subunit boost has the potential to induce not only cytotoxic T lymphocytes but also neutralizing antibody.

Description:

The combination of a live recombinant primer followed by a subunit boost has the potential to induce not only cytotoxic T lymphocytes but also neutralizing antibody.

Volunteers are randomized to one of seven groups to receive immunizations with either ALVAC-HIV vCP300 or ALVAC-RG vCP65 (control), plus simultaneous or sequential boosting with rgp120/HIV-1SF2 or placebo. Immunizations are given at 0, 1, 6, and 9 months or 0, 1, 3, and 6 months. Volunteers are followed for at least 24 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: January 1999
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria

Volunteers must have:

• Normal history and physical exam.

• ELISA and Western blot negative for HIV.

• CD4 count >= 400 cells/mm3.

• Normal urine dipstick with esterase and nitrite.

• Lower risk sexual behavior.

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.

• 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.

• Allergy to egg products or neomycin.

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.

• Prior immunization against rabies.

• History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-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:

• Live attenuated vaccines within 60 days prior to study entry. NOTE: Medically indicated killed or subunit vaccines (e.g., influenza, pneumococcal) do not exclude if administered at least 2 weeks from HIV immunizations.

• Experimental agents within 30 days prior to study entry.

• Prior HIV vaccines.

• Prior rabies immunization.

Prior Treatment:

Excluded:

• Blood products or immunoglobulin within 6 months prior to study entry. Identifiable high-risk behavior for HIV infection, such as

• injection drug use within past 12 months.

• higher or intermediate risk sexual behavior.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• ALVAC-HIV MN120TMGNP (vCP300)

• ALVAC-RG Rabies Glycoprotein (vCP65)

• rgp120/HIV-1 SF-2

Locations

Country	Name	City	State
United States	JHU AVEG	Baltimore	Maryland
United States	UAB AVEG	Birmingham	Alabama
United States	Vanderbilt Univ. Hosp. AVEG	Nashville	Tennessee
United States	Univ. of Rochester AVEG	Rochester	New York
United States	St. Louis Univ. School of Medicine AVEG	Saint Louis	Missouri
United States	UW - Seattle AVEG	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (9)

Bender TJ, Tang J, Rivers C, Mulligan MJ, Kaslow RA. Grouping by HLA class I supertype does not enhance HLA associations with CTL responses to ALVAC-HIV canarypox vaccine components. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 193)

Castillo RC, Arango-Jaramllo S, Humphrey W, Weinhold K, Schwartz DH. Vaccine induced CTL activity correlates with resistant phenotype in an in vitro challenge system. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:95 (abstract no 91)

Evans T, Corey L, Clements-Mann ML, Weinhold K, Belshe RB, Excler JL, Duliege AM. CD8+ CTL induced in AIDS vaccine evaluation group phase I trials using canarypox vectors (ALVAC) encoding multiple HIV gene products (vCP125, vCP205, vCP300) given with or without subunit boost. Int Conf AIDS. 1998;12:277 (abstract no 495/21192)

Evans TG, Keefer MC, Weinhold KJ, Wolff M, Montefiori D, Gorse GJ, Graham BS, McElrath MJ, Clements-Mann ML, Mulligan MJ, Fast P, Walker MC, Excler JL, Duliege AM, Tartaglia J. A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers. J Infect Dis. 1999 Aug;180(2):290-8. — View Citation

Evans TG, Keefer MC, Wolff M, Weinhold K, Excler JL, Duliege AM, Fast P, McElrath MJ, Graham BS, Clements-Mann ML, Mulligan M, Gorse GJ. A canarypox recombinant containing HIV-1 env, gag, pol and nef genes (vCP 300) given with SF-2 rgp120 elicits broad, durable CD8+ CTL in seronegative volunteers. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:180 (abstract no 533)

Evans TG, Keefer MC, Wolff M, Weinhold K, Excler JL, Duliege AM, McNamara J, McElrath JM, Graham BJ, Clements ML, Mulligan M, Belshe RB, Tartaglia J. Immunization of HIV-1 non-infected volunteers with a canarypox recombinant containing HIV-1 env, gag, pol, and nef genes (vCP 300) given simultaneously or followed by recombinant HIV-1 SF2 gp120. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:204 (abstract no 754)

Gorse GJ, Patel GB, Mandava MD, Belshe RB. Vaccine-induced cytotoxic T lymphocytes against human immunodeficiency virus type 1 using two complementary in vitro stimulation strategies. Vaccine. 1999 Dec 10;18(9-10):835-49. — View Citation

Kaslow RA, Rivers C, Goepfert P, Tang J, El Habib R, Weinhold K, Mulligan MJ. Association of HLA class I alleles with cytotoxic T-lymphocyte (CTL) responses to gag and env in recipients of ALVAC-HIV canarypox vaccines. 7th Conference on Retroviruses and Opportunistic Infections. 2000 Jan 30-Feb 2 [Poster 818]

Sabbaj S, Corey L, Evans T, Keefer M, Excler JL, Duliege AM, Mulligan MJ, McGhee JR. Cytokine profiles in human PBMC T cell cultures stimulated with HIV antigens in seronegative volunteers immunized with canarypox expressing HIV antigens and boosted with recombinant SF2 GP120. Conf Adv AIDS Vaccine Dev. 1997 May 4-7:215 (Poster 110)