A Multicenter, Randomized, Placebo-Controlled, Double-Blinded, Phase I Trial to Evaluate the Safety and Immunogenicity of Live Recombinant Canarypox ALVAC-HIV vCP205 Combined With GM-CSF in Healthy, HIV-1 Uninfected Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001090
First received: November 2, 1999
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

To evaluate the safety and immunogenicity of live recombinant canarypox ALVAC-HIV vCP205 in combination with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) at 80 microg and 250 microg. [AS PER AMENDMENT 4/30/99: To study the safety of following 4 ALVAC immunizations with a nucleic acid gag/pol HIV-1 immunogen (APL-400-047, Wyeth-Lederle). To assess the ability of this sequence of immunization to boost the LTL, T-helper cell, and antibody response.] ALVAC-HIV candidate vaccines have induced HIV-specific CTL responses in more than half of recipients in some protocols. Depending on the HIV-1 gene products expressed by the particular ALVAC-HIV candidate vaccine, volunteers have generated anti-Envelope (vCP125, vCP205, and vCP300), anti-Gag (vCP205 and vCP300), and anti-Nef (vCP300) CTL activity. Although 3 to 4 immunizations with the different ALVAC-HIV experimental vaccines induce anti-HIV-1 neutralizing antibodies in a portion, often the majority, of volunteers, the geometric mean titers of these antibodies are modest, usually less than 50. This study will determine whether there is an increase in the anti-HIV antibody titers when GM-CSF is used as an adjuvant with ALVAC-HIV vCP205 and will also examine the kinetics and magnitude of the HIV-specific CTL response.


Condition Intervention Phase
HIV Infections
Biological: APL 400-047
Biological: ALVAC-HIV MN120TMG (vCP205)
Drug: Sargramostim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized, Placebo-Controlled, Double-Blinded, Phase I Trial to Evaluate the Safety and Immunogenicity of Live Recombinant Canarypox ALVAC-HIV vCP205, Combined With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Healthy, HIV-1 Uninfected Volunteers

Resource links provided by NLM:


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

Estimated Enrollment: 36
Study Completion Date: October 1999
Detailed Description:

ALVAC-HIV candidate vaccines have induced HIV-specific CTL responses in more than half of recipients in some protocols. Depending on the HIV-1 gene products expressed by the particular ALVAC-HIV candidate vaccine, volunteers have generated anti-Envelope (vCP125, vCP205, and vCP300), anti-Gag (vCP205 and vCP300), and anti-Nef (vCP300) CTL activity. Although 3 to 4 immunizations with the different ALVAC-HIV experimental vaccines induce anti-HIV-1 neutralizing antibodies in a portion, often the majority, of volunteers, the geometric mean titers of these antibodies are modest, usually less than 50. This study will determine whether there is an increase in the anti-HIV antibody titers when GM-CSF is used as an adjuvant with ALVAC-HIV vCP205 and will also examine the kinetics and magnitude of the HIV-specific CTL response.

In this randomized, placebo-controlled, double-blinded study volunteers receive ALVAC-HIV vCP205 at 10^6.3 TCID50 or placebo and GM-CSF or placebo by intramuscular injection at Months 0, 1, 3, and 6 as follows:

Group A: vCP205 plus GM-CSF placebo (10 volunteers) Group B: vCP205 plus 80 microg GM-CSF (10 volunteers) Group C: vCP205 plus 250 microg GM-CSF (10 volunteers) Group D: vcP205 placebo plus GM-CSF placebo (6 volunteers). [AS PER AMENDMENT 04/30/99: Boosting with APL-400-047 HIV-1 gag/pol DNA is added for volunteers who have received all scheduled immunization in the original protocol. Volunteers in Groups A, B, and C will receive booster intramuscular injections of DNA vaccine at Months 0 and 1, those in Group D will receive DNA control (bupivacaine carrier alone) at Months 0 and 1].

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

Volunteers must have:

  • Negative ELISA for HIV within 8 weeks prior to immunization.
  • CD4 count of 400 cells/mm3 or higher.
  • Normal history and physical examination.
  • Viable EBV line prior to initial immunization. [AS PER AMENDMENT 4/30/99:
  • Negative anti-dsDNA antibodies (for volunteers receiving booster vaccine).]

Exclusion Criteria

Co-existing Condition:

Volunteers with the following conditions or symptoms are excluded:

  • Medical or psychiatric condition or occupational responsibilities that preclude compliance with the protocol.
  • Recent suicidal ideation or psychosis.
  • Active syphilis. NOTE:
  • If the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible.
  • Active tuberculosis. NOTE:
  • Volunteers who have a positive PPD and a normal chest x-ray showing no evidence of TB and who do not require INH therapy are eligible.
  • Positive for hepatitis C antibody or hepatitis B surface antigen.
  • Allergy to eggs, neomycin, or thimerosal. [AS PER AMENDMENT 4/30/99:
  • Hypersensitivity to bupivacaine or other amide-type anesthetics (e.g., lidocaine, mepivacaine) for volunteers receiving booster vaccine).]

Concurrent Medication:

Excluded:

Lithium or cimetidine.

Volunteers with the following prior conditions are excluded:

  • History of immunodeficiency, chronic illness, or autoimmune disease.
  • History of cancer unless there has been surgical excision with reasonable assurance of cure.
  • History of suicide attempts or past psychosis.
  • History of anaphylaxis or other serious adverse reactions to vaccines.
  • History of serious allergic reaction to any substance requiring hospitalization or emergent care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).

[AS PER AMENDMENT 11/13/97:

  • History of cardiac disease or cardiac arrhythmias.]

Prior Medication:

Excluded:

  • Live attenuated vaccines within 60 days of study. NOTE:
  • Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from HIV immunizations.
  • Experimental agents within 30 days prior to study.
  • Blood products or immunoglobulin in the past 6 months.
  • HIV-1 vaccines or placebo as part of a previous HIV vaccine trial.
  • Immunosuppressive medications.

Risk Behavior:

Excluded:

Volunteers with an identifiable higher-risk behavior for HIV infection (i.e., AVEG Risk Group C or D), including a history of injection drug use within 12 months prior to enrollment or higher-risk sexual behavior as defined by the AVEG.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001090

Locations
United States, Alabama
UAB AVEG
Birmingham, Alabama, United States, 35294
United States, Maryland
JHU AVEG
Baltimore, Maryland, United States
United States, New York
Univ. of Rochester AVEG
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt Univ. Hosp. AVEG
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Investigators
Study Chair: T Evans
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001090     History of Changes
Other Study ID Numbers: AVEG 033, 10582
Study First Received: November 2, 1999
Last Updated: May 16, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Reference Values
Granulocyte-Macrophage Colony-Stimulating Factor
AIDS Vaccines
HIV Seronegativity
Dose-Response Relationship, Immunologic
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

ClinicalTrials.gov processed this record on September 18, 2014