Clinical trial NCT00027261: Safety and Immune Response Study of High-Dose Canarypox ALVAC-HIV Vaccine in Healthy, HIV Uninfected Adults
Official title: A Phase I Trial to Evaluate the Safety, Tolerability and Immunogenicity of High-Dose Live Recombinant Canarypox ALVAC-HIV Vaccine (vCP1452) in Healthy, HIV-1 Uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
HIV Seronegativity
Keywords: Vaccines, Synthetic
HIV-1
AIDS Vaccines
CD8-Positive T-Lymphocytes
HIV Seronegativity
Avipoxvirus
Dose-Response Relationship, Immunologic
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-11-30
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to see if the experimental vaccine, ALVAC-HIV (vCP1452) is safe and to study how the immune system responds to the vaccine. This trial is designed to determine whether a higher vaccine dose (6 times the usual dose) will elicit a higher immune response.

As of May 2001, over 200 people received the ALVAC-HIV (vCP1452) vaccine at the lower dose. The higher dose of the vaccine to be used in this study has not been given to humans previously. High doses of a similar vaccine have been given to a few people without serious side effects. In a recent study done in mice, higher doses of ALVAC-HIV produced stronger immune responses. It is possible that the doses of ALVAC-HIV given to humans are below the amount needed for the maximum immune response. Because the exact relationship between an increased immune response and its effectiveness in preventing HIV infection is uncertain, the HVTN will use the highest dose that can be manufactured.

Detailed description: To date, adverse reactions to immunization with the various ALVAC-HIV candidate vaccines, including ALVAC-HIV (vCP1452), have been similar to those observed in healthy adults who have received other licensed vaccines of similar types. In a previous trial, even high doses of recombinant ALVAC vaccine were well tolerated in a group of participants that were significantly immunocompromised. In a recent study done in mice concerning dose escalation using the ALVAC-HIV vectors, the data demonstrated more robust immune responses with higher doses of ALVAC-HIV (vCP1452) in mice. It is certainly possible that the doses of ALVAC-HIV given to humans are well below the amount needed for a maximal cytotoxic T lymphocyte (CTL) response. As the predictive value of a CTL response is at present unknown with respect to its efficacy in preventing or ameliorating HIV acquisition or infection, the HVTN will utilize the highest dose that can be currently manufactured.

All study products are to be administered intramuscularly. Participants will receive 1 of 3 injections. Group A will receive a high dose of vaccine, group B will receive a low dose of vaccine, and group C will receive a placebo. Participants are inoculated at 4 time points. Assessment of product safety includes clinical observation, monitoring of hematological, chemical, and immunologic parameters, and a social harms questionnaire. Safety will be evaluated by monitoring of participants for local and systemic adverse reactions during the course of the trial. Participants will be monitored longitudinally for HIV-specific serologic and cellular immune responses.

Eligibility criteria: Inclusion Criteria

Participants may be eligible for this study if they:

* Are between the ages of 18 and 60.
* Are in good general health.
* Have a CD4 count of 400 or more cells/mm3.
* Do not have hepatitis C or active hepatitis B.
* Have had a negative HIV blood test within 8 weeks prior to enrollment.
* Use approved methods of contraception.
* Have access to a participating site and are available for follow-up for 18 months.
* Complete a questionnaire evaluating the participant's understanding of the study prior to enrollment.
* Give written informed consent.

Exclusion Criteria

Participants may not be eligible for this study if they:

* Are pregnant or breast-feeding.
* Have received a live vaccine within 30 days prior to enrollment.
* Have received a killed vaccine or allergy treatment with injections within 14 days prior to study vaccine.
* Have used experimental research agents within 30 days prior to enrollment.
* Have received HIV-1 vaccines or placebo in a previous HIV vaccine trial.
* Have received blood products 120 days before HIV screening.
* Have received immunoglobulin 60 days before HIV screening.
* Have a history of serious harmful reactions to vaccines.
* Have a history of disease of the immune system.
* Have a history of cancer, unless it has been surgically removed and in the estimate of the investigator is not likely to happen again during the study period.
* Are using or have used (within past 6 months) drugs that interfere with the immune system.
* Have a history of type I or type II diabetes.
* Have thyroid disease.
* Have unstable asthma.
* Are currently taking preventive anti-TB therapy.
* Have a seizure disorder.
* Have a bleeding disorder that was diagnosed by a physician.
* Have had their spleen removed.
* Have angioedema with serious episodes.
* Have active syphilis.
* Have hypertension.
* Have mental problems that would interfere with the protocol.
* Have any other problems that, in the judgment of the investigator, would interfere with the study.
* Have a body mass index less than 20.
* Are allergic or sensitive to egg products.
* Have active tuberculosis.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: San Francisco
country: United States
facility: San Francisco Vaccine and Prevention CRS
state: California
city: San Francisco
country: United States
facility: UCSF, Gen. Clinical Research Ctr., Mt. Zion Hosp.
state: California
city: Baltimore
country: United States
facility: Project Brave HIV Vaccine CRS
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hosp. CRS
state: Massachusetts
city: Boston
country: United States
facility: Fenway Community Health Clinical Research Site (FCHCRS)
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis Univ Health Sciences Ctr
state: Missouri
city: New York
country: United States
facility: NY Blood Ctr./Union Square CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester HVTN CRS
state: New York
city: Providence
country: United States
facility: Miriam Hospital's HVTU
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Vaccine CRS
state: Tennessee
city: Annandale
country: United States
facility: Infectious Diseases Physicians, Inc.
state: Virginia
city: Seattle
country: United States
facility: FHCRC/UW Vaccine CRS
state: Washington
Study officials:
name: Paul Goepfert
role: STUDY_CHAIR
References:
citation: Goepfert PA, Horton H, McElrath MJ, Gurunathan S, Ferrari G, Tomaras GD, Montefiori DC, Allen M, Chiu YL, Spearman P, Fuchs JD, Koblin BA, Blattner WA, Frey S, Keefer MC, Baden LR, Corey L; NIAID HIV Vaccine Trials Network. High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis. 2005 Oct 1;192(7):1249-59. doi: 10.1086/432915. Epub 2005 Aug 31.