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Safety of and Immune Response to an HIV Preventive Vaccine (HIV-1 Gag DNA Alone or With IL-15 DNA) Given With or Without 2 Different Booster Vaccinations 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:
NCT00115960
First received: June 26, 2005
Last updated: March 26, 2012
Last verified: March 2012
  Purpose

The purpose of this study is to determine the safety of and immune response to an experimental HIV vaccine, HIV-1 gag DNA, with and without an IL-15 DNA adjuvant (at escalating doses of 100, 500, and 1500 mcg). This study will also test the safety of and immune response to the HIV-1 gag DNA vaccine plus IL-15 DNA adjuvant given with or without 2 other adjuvant-containing booster vaccines.


Condition Intervention Phase
HIV Infections
Biological: HIV-1 gag DNA
Biological: IL-15 DNA adjuvant
Biological: IL-12 DNA adjuvant
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Official Title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of HIV-1 Gag DNA Vaccine Alone or With IL-15 DNA, Boosted With HIV-1 Gag DNA + IL-15 DNA or HIV-1 Gag DNA + IL-12 DNA, 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:
  • Local and systemic reactogenicity signs and symptoms, as assessed after each injection [ Time Frame: 12 months postinjection for Part A, and 15 months after the first injection in Part B ] [ Designated as safety issue: Yes ]
  • Laboratory measures of safety, as assessed after each injection [ Time Frame: 12 months postinjection for Part A, and 15 months after the first injection in Part B ] [ Designated as safety issue: Yes ]
  • Adverse and serious adverse experiences, as assessed after each injection [ Time Frame: 12 months postinjection for Part A, and 15 months after the first injection in Part B ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • HIV-specific cellular responses by IFN-gamma ELISpot [ Time Frame: 12 months postinjection for Part A, and 15 months after the first injection in Part B ] [ Designated as safety issue: Yes ]
  • HIV binding antibody by ELISA [ Time Frame: 12 months postinjection for Part A, and 15 months after the first injection in Part B ] [ Designated as safety issue: Yes ]
  • Social impact variables [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Enrollment: 120
Study Completion Date: July 2008
Arms Assigned Interventions
Experimental: 1
Group 1 will receive 3 vaccinations of the HIV-1 gag DNA vaccine, or placebo. Vaccinations will be given at Months 0, 1, and 3.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Experimental: 2
Group 2 will receive 3 vaccinations of either the HIV-1 gag DNA vaccine with a low dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Biological: IL-15 DNA adjuvant
Cytokine injection
Experimental: 3
Group 3 will receive 3 vaccinations of either the HIV-1 gag vaccine with a medium dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Biological: IL-15 DNA adjuvant
Cytokine injection
Experimental: 4
Group 4 will receive 3 vaccinations of either the HIV-1 gag vaccine with a high dose of IL-15 adjuvant, or a placebo. Vaccinations will be given at Months 0, 1, and 3.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Biological: IL-15 DNA adjuvant
Cytokine injection
Experimental: 5
In Part B, Group 5 will receive 5 vaccinations of either the HIV-1 gag vaccine plus IL-15 DNA, or placebo. Vaccinations will occur at Months 0, 1, 3, 6, and 9.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Biological: IL-15 DNA adjuvant
Cytokine injection
Experimental: 7
In Part B, Group 7 will receive 3 vaccinations of the HIV-1 gag vaccine with a high dose of IL-15 adjuvant (maximum tolerated dose from Part A) followed by 2 vaccinations of the gag DNA vaccine with IL-12 DNA adjuvant. Some participants will receive placebo instead of this vaccine regimen. For Group 7, the HIV-1 gag vaccine with IL-15 adjuvant vaccinations will be given at Months 0, 1, and 3, and booster vaccinations will be given at Months 6 and 9.
Biological: HIV-1 gag DNA
DNA vaccine containing the HIV gene gag
Biological: IL-15 DNA adjuvant
Cytokine injection
Biological: IL-12 DNA adjuvant
Cytokine injection

Detailed Description:

The HIV epidemic is a major global health challenge, causing tremendous human suffering and economic loss throughout the world. The need for a safe, effective, and affordable HIV preventive vaccine is critical. This 2-part study will determine the safety and immunogenicity of the experimental HIV vaccine HIV-1 gag DNA with or without IL-15 adjuvant, boosted with either the HIV-1 gag DNA and IL-15 adjuvant vaccine or the HIV-1 gag DNA and IL-12 adjuvant vaccine.

There are two parts to this study. Part A will last 12 months. In Part A, 48 participants will be randomly assigned to 1 of 4 groups in sequential order (dose escalation). All participants will receive 3 vaccinations. Group 1 will receive 3 vaccinations of the HIV-1 gag DNA vaccine or placebo. Group 2 will receive 3 vaccinations of either the HIV-1 gag DNA vaccine with a low dose of IL-15 adjuvant or a placebo. Group 3 will receive 3 vaccinations of either the HIV-1 gag vaccine with a medium dose of IL-15 adjuvant or a placebo. Group 4 will receive 3 vaccinations of either the HIV-1 gag vaccine with a high dose of IL-15 adjuvant or a placebo. Vaccinations will be given at Months 0, 1, and 3. There will be 11 study visits in Part A. A physical exam, pregnancy prevention counseling, medication history, and adverse event reporting will occur at most visits. Urine and blood collection will occur at some visits. Participants will also be asked to complete questionnaires at certain visits.

Part B will last 15 months. In Part B, 72 participants will be randomly assigned to 1 of 2 groups. All Part B participants will receive 5 vaccinations. Group 5 will receive 5 vaccinations of either the HIV-1 gag vaccine plus IL-15 DNA or placebo; the vaccinations will occur at Months 0, 1, 3, 6, and 9. Group 7 will receive 3 vaccinations of the HIV-1 gag vaccine with a high dose of IL-15 adjuvant (maximum tolerated dose from Part A) followed by 2 vaccinations of the gag DNA vaccine with IL-12 DNA adjuvant. Some participants will receive placebo instead of this vaccine regimen. For Group 7, the HIV-1 gag vaccine with IL-15 adjuvant vaccinations will be given at Months 0, 1, and 3, and booster vaccinations will be given at Months 6 and 9. There will be 13 study visits in Part B. A physical exam, pregnancy prevention counseling, medication history, and adverse event reporting will occur at most visits. Urine and blood collection will occur at some visits. Participants will also be asked to complete questionnaires at certain visits.

  Eligibility

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

Note: Group 6 has been removed from Part B of the protocol as of the 04/11/06 amendment. Because a regimen similar to Group 6's regimen is being tested in HVTN 060, the vaccine manufacturer decided that Group 6's regimen was not a priority for testing.

Inclusion Criteria:

  • HIV uninfected
  • Access to a participating HIV Vaccine Trials Unit (HVTU)
  • Willing to receive HIV test results
  • Willing and able to comply with all study requirements
  • In good general health
  • Willing to use acceptable methods of contraception for at least 21 days prior to study entry and until the last study visit. More information about this criterion can be found in the protocol.
  • Hepatitis B surface antigen negative
  • Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive

Exclusion Criteria:

  • HIV vaccines in prior HIV vaccine trial
  • Immunosuppressive medications within 168 days prior to first vaccination
  • Blood products within 120 days prior to first vaccination
  • Immunoglobulin within 60 days prior to first vaccination
  • Live attenuated vaccines within 30 days prior to first vaccination
  • Investigational research agents within 30 days prior to first vaccination
  • Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration, or allergy treatment with antigen injections within 30 days prior to first vaccination
  • Current tuberculosis (TB) prophylaxis or therapy
  • Clinically significant medical condition, physical exam findings, abnormal laboratory results, or past medical history with clinically significant implications for current health
  • Any medical, psychiatric, or social condition that, in the opinion of the investigator, may interfere with the study
  • Any occupational or other responsibility that, in the opinion of the investigator, may interfere with the study
  • Diagnosis of allergy to amide-type local anesthetics
  • Serious adverse reaction to vaccines, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, or abdominal pain. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
  • Autoimmune disease or immunodeficiency
  • Unstable asthma
  • Diabetes mellitus Type 1 or Type 2. Participants with histories of isolated gestational diabetes are not excluded.
  • Thyroid disease requiring treatment in the past 12 months
  • Serious angioedema within the last 3 years
  • Uncontrolled hypertension
  • Body mass index (BMI) of 40 or greater OR BMI of 35 or greater, when certain other criteria are met. More information about these criteria can be found in the protocol.
  • Bleeding disorder
  • Cancer. Participants with surgically removed cancer that, in the opinion of the investigator, is unlikely to recur are not excluded.
  • Seizure disorder requiring medication within the past 3 years
  • Absence of the spleen
  • Psychiatric condition, including psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
  • Pregnant or breastfeeding, or plan to become pregnant during the study

Exclusion Criteria for Part B Participants:

  • Diagnosis of allergy to egg products
  • Diagnosis of allergy to yeast-derived products
  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: NCT00115960

Locations
United States, Massachusetts
Brigham and Women's Hosp. CRS
Boston, Massachusetts, United States, 02115
United States, New York
NY Blood Ctr./Bronx CRS
Bronx, New York, United States, 10456
HIV Prevention & Treatment CRS
New York, New York, United States, 10032
NY Blood Ctr./Union Square CRS
New York, New York, United States, 10003
Univ. of Rochester HVTN CRS
Rochester, New York, United States, 14642-0001
United States, Rhode Island
Miriam Hospital's HVTU
Providence, Rhode Island, United States
Brazil
Sao Paulo HVTU - CRT DST/AIDS CRS
San Paulo, Brazil
Sponsors and Collaborators
Investigators
Study Chair: Lindsey Baden, MD Harvard University
Study Chair: Xia Jin, MD, PhD University of Rochester
  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: NCT00115960     History of Changes
Other Study ID Numbers: HVTN 063, 10058
Study First Received: June 26, 2005
Last Updated: March 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
IL-12
IL-15
HIV Seronegativity
HIV Preventive Vaccine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014