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A Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox-gp160 MN (ALVAC vCP125, HIV-1 gp160 MN) in HIV-1 Uninfected Adult Volunteers
This study has been completed.

First Received on November 2, 1999.   Last Updated on June 23, 2005   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator: Pasteur Merieux Connaught
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000813
  Purpose

Part A: To evaluate the safety and immunogenicity of ALVAC vCP125 HIV-1 gp160 MN live canarypox recombinant vaccine (ALVAC gp160 MN) versus a recombinant canarypox expressing the rabies glycoprotein (ALVAC rabies glycoprotein) as a control in healthy, HIV-1 uninfected adult volunteers.

Part B: To evaluate the schedule of two immunizations with ALVAC gp160 MN for optimal immunogenicity.

Amendment: 12/22/93: To determine whether ALVAC gp160 MN in combination with SF-2 rgp120 subunit protein is capable of generating humoral and cellular immune responses of greater intensity and longer duration than either vaccine administered alone.

A canarypox-vectored vaccine (ALVAC) that expresses the gp160 antigen of the HIV-1 MN strain might satisfy many criteria for an affordable HIV vaccine. Per 12/22/93 amendment: Cellular responses have been augmented by the combination of two recombinant vaccines, especially in vaccinia naive individuals.


Condition Intervention Phase
HIV Infections
Biological: ALVAC-HIV gp160MN (vCP125)
Biological: ALVAC-RG Rabies Glycoprotein (vCP65)
Biological: rgp120/HIV-1 SF-2
Phase I

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox-gp160 MN (ALVAC vCP125, HIV-1 gp160 MN) in HIV-1 Uninfected Adult Volunteers

Resource links provided by NLM:


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

Estimated Enrollment: 28
Detailed Description:

A canarypox-vectored vaccine (ALVAC) that expresses the gp160 antigen of the HIV-1 MN strain might satisfy many criteria for an affordable HIV vaccine. Per 12/22/93 amendment: Cellular responses have been augmented by the combination of two recombinant vaccines, especially in vaccinia naive individuals.

In Part A, 28 healthy volunteers (15 vaccinia-immune and 13 vaccinia-naive) are randomized to receive intramuscular injections of ALVAC gp160 MN at a dose of 1 million TCID50 or ALVAC rabies glycoprotein as a control at months 0 and 2. In Part B, 90 healthy volunteers (60 vaccinia immune and 30 vaccinia naive) are randomized to receive ALVAC gp160 MN at a dose of 10 million TCID50 or ALVAC rabies glycoprotein control, on an immunization schedule of either month 0 and 1 or 0 and 2. For Part B, half of the patients receiving ALVAC gp160 MN, as well as approximately half of those receiving control vaccine, will receive booster immunizations with SF-2 rgp120 subunit protein, if available, at months 9 and 12; the other half will receive booster immunizations with the same preparation as they received for their first two immunizations. In Part A, all control volunteers except one within each control group receive SF-2 rgp120 subunit protein at months 9 and 12. An additional group of 10 volunteers will receive four injections of SF-2 rgp120 subunit protein at months 0, 1, 6 and 12. Part B will begin whenever the higher dose of ALVAC gp160 MN becomes available (at least 4 weeks after initiation of Part A). Volunteers are followed for at least 18 months. Per 06/10/94 addendum, volunteers will be contacted once or twice per year for at least 5 years to check on health status.

  Eligibility

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

Inclusion Criteria

Subjects must have:

  • Normal history and physical exam.
  • Negative ELISA for HIV.
  • CD4 count >= 400 cells/mm3.
  • Normal urine dipstick with esterase and nitrite.
  • Lower risk sexual behavior.

NOTE:

  • No more than 10 percent of participants will be older than 50 years.

Prior Medication:

Allowed:

  • Prior smallpox vaccination.

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.
  • Allergy to egg products or neomycin.
  • Occupational exposure to birds.

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. It is STRONGLY RECOMMENDED that any activity that might expose subject to HIV (unprotected sex or needle sharing) be avoided.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000813

Locations
United States, Maryland
Johns Hopkins Univ / School of Hygiene & Public Health
Baltimore, Maryland, United States, 212051901
United States, Missouri
St Louis Univ School of Medicine
St. Louis, Missouri, United States, 63104
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
Pasteur Merieux Connaught
Investigators
Study Chair: Clements ML
  More Information

Publications:
Clements-Mann ML, Weinhold K, Matthews TJ, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Hsieh RH, Mestecky J, Zolla-Pazner S, Mascola J, Schwartz D, Siliciano R, Corey L, Wright PF, Belshe R, Dolin R, Jackson S, Xu S, Fast P, Walker MC, Stablein D, Excler JL, Tartaglia J, Paoletti E, et al. Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group. J Infect Dis. 1998 May;177(5):1230-46.
Ferrari G, Humphrey W, McElrath MJ, Excler JL, Duliege AM, Clements ML, Corey LC, Bolognesi DP, Weinhold KJ. Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1396-401.
Zolla-Pazner S, Alving C, Belshe R, Berman P, Burda S, Chigurupati P, Clements ML, Duliege AM, Excler JL, Hioe C, Kahn J, McElrath MJ, Sharpe S, Sinangil F, Steimer K, Walker MC, Wassef N, Xu S. Neutralization of a clade B primary isolate by sera from human immunodeficiency virus-uninfected recipients of candidate AIDS vaccines. J Infect Dis. 1997 Apr;175(4):764-74.
Egan MA, Pavlat WA, Tartaglia J, Paoletti E, Weinhold KJ, Clements ML, Siliciano RF. Induction of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T lymphocyte responses in seronegative adults by a nonreplicating, host-range-restricted canarypox vector (ALVAC) carrying the HIV-1MN env gene. J Infect Dis. 1995 Jun;171(6):1623-7.

ClinicalTrials.gov Identifier: NCT00000813     History of Changes
Other Study ID Numbers: AVEG 012A, AVEG 012B
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
HIV Envelope Protein gp160
HIV Envelope Protein gp120
AIDS Vaccines
HIV Seronegativity
Avipoxvirus
HIV Preventive Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Krestin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers
Radiation-Protective Agents
Protective Agents

ClinicalTrials.gov processed this record on February 12, 2012