Safety of and Immune Response to a Combination HIV Vaccine Regimen in HIV Uninfected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00073216
First received: November 18, 2003
Last updated: May 3, 2012
Last verified: May 2012
  Purpose

To prevent HIV infection, a vaccine that produces strong HIV-specific humoral (B-cell) and cellular (T-cell) immune system responses is desirable. The purpose of this study is to test the safety of and immune response to a novel combination HIV vaccine in HIV uninfected adults. This study will also test the safety of and immune response to a protein vaccine given alone.


Condition Intervention Phase
HIV Infections
Biological: Clade B gag DNA/PLG and env DNA/PLG Microparticles
Biological: Clade B Recombinant, Oligomeric gp140/MF59 Adjuvant
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Primary Purpose: Prevention
Official Title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Clade B Gag DNA/PLG and Env DNA/PLG Microparticles Vaccine and a Clade B Recombinant, Oligomeric gp140/MF59 Adjuvant Vaccine in Healthy, HIV-1 Uninfected Adult Participants

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences)
  • immunogenicity (presence of HIV-specific immune response as measured by the interferon-gamma ELISpot, FACS Intracellular Cytokine Staining [ICS], neutralizing antibody, or HIV antigen-binding ELISA assays)
  • social impacts (negative experiences or problems reported by the participants)

Enrollment: 96
Study Completion Date: September 2007
Detailed Description:

The development of a vaccine eliciting HIV-specific humoral and cellular immune responses is desirable for the prevention of HIV infection. This study will investigate a combination vaccine regimen consisting of priming with DNA followed by boosting with a recombinant envelope glycoprotein adjuvanted in MF59.

All participants will be followed for 15 months. Participants enrolled in Groups 1, 2, 3, and 4 will receive either the vaccine or placebo. Study visits will be completed at initial entry; five visits every 14 days for the first 2.5 months; and visits at Months 4, 4.5, 6, 6.5, 9, 9.5, 12, and 15. All participants will undergo physical exams, urine collection, and blood tests to assess safety, HIV infection, and immune responses to injections. Risk reduction/pregnancy prevention counseling will be given at every study visit. Participants will also be asked to complete questionnaires about outside testing and beliefs at certain visits.

There are two parts to this study. In Part A, participants will be sequentially assigned to one of three groups. Each group will receive injections of different amounts of either DNA vaccine or placebo at entry, Month 1, and Month 2. This is followed by identical injections of glycoprotein/adjuvant or placebo at Months 6 and 9. Group 1 will receive 250 mcg each of the gag and env DNA plasmid with microparticle vaccine; Group 2 will receive 500 mcg of each vaccine; Group 3 will receive 1000 mcg of each vaccine. Participants will be enrolled sequentially from low to high dose beginning with Group 1.

In Part B, Group 4 will begin the second part of the study simultaneously after safety review of all participants in Part A. Group 4 participants will receive identical injections of either DNA vaccine or placebo at entry and at Months 1, 2, 6, and 9.

Group 5 will begin enrollment after enrollment is completed for Groups 1, 2, 3, and 4. Group 5 participants will receive identical injections of either glycoprotein/adjuvant or placebo at study entry and at Months 3 and 9. There will be 11 study visits for Group 5 participants; they will occur at screening, study entry, and Months 0.5, 2, 3, 3.5, 6, 9, 9.5, 12, and 15. A physical exam and risk reduction/pregnancy prevention counseling will occur at all visits; participants will be asked at every visit about any adverse events they may have experienced. Blood and urine collection will occur at selected visits. Participants will be also asked to complete questionnaires about outside testing and beliefs at certain visits.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Note: As of 07/01/05, Group 5 will begin enrollment after enrollment into Groups 1, 2, 3, and 4 is completed.

Inclusion Criteria

  • Understanding of vaccination procedure
  • Willing to receive HIV test results and provide informed consent
  • Good general health
  • HIV negative
  • Hepatitis B surface antigen negative
  • Anti-hepatitis C virus (HCV) antibody negative, or negative for HCV PCR if the anti-HCV is positive
  • Not pregnant and agrees to use acceptable forms of contraception

Exclusion Criteria

  • Received HIV vaccines or placebo in a prior HIV vaccine trial
  • Immunosuppressive medications within 168 days prior to study
  • Blood products within 120 days prior to study
  • Immunoglobulin within 60 days prior to study
  • Live attenuated vaccines within 30 days prior to study
  • Investigational research agents within 30 days prior to study
  • Medically indicated subunit or killed vaccines within 14 days prior to study
  • Current anti-tuberculosis prophylaxis or therapy
  • Anaphylaxis or other serious adverse reactions to vaccines; a person who had an adverse reaction to pertussis vaccine as a child is not excluded
  • Autoimmune disease or immunodeficiency
  • Active syphilis infection
  • Unstable asthma (e.g., use of oral, orally inhaled, or intravenous corticosteroids, emergent care, urgent care, hospitalization or intubation during the past 2 years)
  • Diabetes mellitus; a participant with past gestational diabetes is not excluded
  • Thyroid disease, including removal of thyroid and diagnoses requiring medication
  • Serious angioedema
  • Uncontrolled hypertension
  • Diagnosis of bleeding disorder
  • Malignancy, except those with a surgical excision and subsequent observation period that in the investigator's estimate has a reasonable assurance of sustained cure and/or is unlikely to recur during the period of the study
  • Seizure disorder requiring medication within the last 3 years
  • Absence of the spleen
  • Mental illness that would interfere with compliance with the protocol
  • Breastfeeding
  • Unprotected rectal or vaginal sex with a partner known to be HIV infected within 6 months of enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00073216

Locations
United States, Missouri
Saint Louis Univ. School of Medicine, HVTU
St. Louis, Missouri, United States
United States, Rhode Island
Miriam Hospital's HVTU
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232
United States, Washington
FHCRC/UW Vaccine CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Paul Spearman Vanderbilt University
Study Chair: Michelle Lally Brown University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00073216     History of Changes
Other Study ID Numbers: HVTN 049, 10054
Study First Received: November 18, 2003
Last Updated: May 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
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 April 17, 2014