Safety of and Immune Response to a DNA HIV Vaccine (pGA2/JS7) Boosted With a Modified Vaccinia HIV Vaccine (MVA/HIV62) in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00301184
First received: March 8, 2006
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to determine the safety of and immune response to a DNA HIV vaccine, pGA2/JS7, followed by a modified vaccinia (smallpox) HIV vaccine, MVA/HIV62, in HIV uninfected adults.


Condition Intervention Phase
HIV Infections
Biological: pGA2/JS7 DNA
Biological: Modified vaccinia Ankara/HIV62
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of pGA2/JS7 DNA Vaccine and Recombinant Modified Vaccinia Ankara/HIV62 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) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Immunogenicity, as defined by the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Social impacts (negative experiences or problems reported by the participants) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 120
Study Start Date: April 2006
Study Completion Date: December 2008
Arms Assigned Interventions
Experimental: 1A
One 0.3 mg dose of DNA HIV vaccine or placebo administered at study entry and Month 2, followed by one dose of 1x10^7 TCID50 MVA or placebo at Months 4 and 6
Biological: pGA2/JS7 DNA
DNA Vaccine
Biological: Modified vaccinia Ankara/HIV62
Recombinant Modified Ankara Vaccine
Other Name: MVA
Experimental: 1B
One 3.0 mg dose of DNA HIV vaccine or placebo administered at study entry and Month 2, followed by one dose of 1x10^8 TCID50MVA or placebo administered at Months 4 and 6
Biological: pGA2/JS7 DNA
DNA Vaccine
Biological: Modified vaccinia Ankara/HIV62
Recombinant Modified Ankara Vaccine
Other Name: MVA
Experimental: 2A
One MTD (determined in Part 1) of DNA HIV vaccine or placebo administered at study entry. One dose of placebo or MTD of MVA at Months 2 and 6
Biological: pGA2/JS7 DNA
DNA Vaccine
Biological: Modified vaccinia Ankara/HIV62
Recombinant Modified Ankara Vaccine
Other Name: MVA
Experimental: 2B
One dose of placebo or MTD of MVA administered at study entry and Months 2 and 6
Biological: Modified vaccinia Ankara/HIV62
Recombinant Modified Ankara Vaccine
Other Name: MVA

Detailed Description:

The worldwide HIV/AIDS epidemic may only be controlled through a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, easily produced in large quantities, and stable for long periods of time. Recombinant modified vaccinia Ankara vaccines have been shown to be safe in humans, and immunogenicity after administration of both vaccines has been encouraging. When used together, a more robust immunologic response was associated with DNA HIV vaccine administration followed by modified vaccinia vaccine administration, compared to using either DNA or vaccinia vaccine alone. This study will evaluate the safety and immunogenicity of an experimental DNA HIV vaccine prime, pGA/JS7, followed by a similarly structured modified vaccinia boost, MVA/HIV62, in HIV uninfected adults. Participants in this study will be recruited only in the United States.

This study will be divided into 2 parts. Each participant will be involved with their part of study for 1 year. Participants in Part 1 will be randomly assigned to one of two different vaccination groups. Group 1A participants will be randomly assigned to receive either placebo or 2 lower doses of the DNA HIV vaccine (DNA) at study entry and Month 2, followed by 2 lower doses of the modified vaccinia vaccine (MVA) at Months 4 and 6. Group 1B will not enroll until safety and immunogenicity data from Group 1A have been evaluated. Group 1B participants will receive either placebo or two higher doses of DNA at study entry and Month 2, followed by two higher doses of MVA at Months 4 and 6.

Enrollment into Part 2 will begin only after safety data from Part 1 are reviewed. In Part 2, participants will be randomly assigned to one of two different vaccination groups. Within each group, participants will be randomly assigned to receive some series of vaccines or placebo. Group 2A participants will receive either placebo or the maximum tolerated dose (MTD) from Part 1 of DNA at study entry and MTD of MVA at Months 2 and 6. Group 2B participants will receive MTD of MVA at study entry and Months 2 and 6.

There will be 12 study visits over 12 months for Groups 1 and 2. There will be 11 study visits over 12 months for Groups 3 and 4. Medication history, a physical exam, an interview, HIV and pregnancy prevention counseling, and adverse events reporting will occur at all visits. Blood and urine collection and an electrocardiogram (ECG) will occur at selected visits.

  Eligibility

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

Inclusion Criteria:

  • HIV uninfected
  • Has access to a participating HIV Vaccine Trials Unit (HVTU) and is willing to be followed for the duration of the study
  • Understands vaccination procedure
  • Willing to receive HIV test results
  • Good general health
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • Received HIV vaccines in prior HIV vaccine trial
  • Received vaccinia vaccine. More information on this criterion can be found in the protocol.
  • Recreational cocaine or methamphetamine use within 12 months prior to study entry
  • Immunosuppressive medications within 168 days prior to first study vaccine administration. Participants who use corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
  • Blood products within 120 days prior to first study vaccine administration
  • Immunoglobulin within 60 days prior to first study vaccine administration
  • Live attenuated vaccines within 30 days prior to first study vaccine administration
  • Investigational research agents within 30 days prior to first study vaccine administration
  • Subunit or killed vaccines within 14 days (for influenza or pneumococcal vaccines) or 30 days (for allergy treatment with antigen injections) prior to first study vaccine administration
  • Current tuberculosis prophylaxis or therapy
  • Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
  • Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
  • Any job-related responsibility that would interfere with the study
  • Allergy to egg products
  • Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
  • History of or known active cardiac disease. More information on this criterion can be found in the protocol.
  • Electrocardiogram (ECG) with clinically significant findings OR features that would interfere with assessments for myocarditis or pericarditis. More information on this criterion can be found in the protocol.
  • Two or more of the following cardiac risk factors: elevated blood cholesterol (defined as fasting low density lipoprotein [LDL] of greater than 160 mg/dl); first-degree relative (e.g., mother, father, brother, sister) who had coronary artery disease before the age of 50; current smoker; or body mass index (BMI) greater than 35
  • Autoimmune disease or immunodeficiency
  • Active syphilis infection. Participants whose syphilis infection was fully treated at least 6 months prior to study entry are not excluded.
  • Severe and unstable asthma
  • Diabetes mellitus type 1 or 2
  • Thyroid disease requiring treatment
  • Serious angioedema within the past 2 years
  • Uncontrolled hypertension OR systolic blood pressure (BP) of 150 mmHg or greater or diastolic BP of 100 mmHg or greater
  • BMI greater than 40
  • Bleeding disorder
  • Cancer. If a participant has had surgery to remove the cancer and, in the opinion of the investigator, the cancer is not likely to recur during the study period, the participant is not excluded.
  • Seizure disorder
  • Asplenia
  • Mental illness that would interfere with compliance with the protocol
  • Other conditions that, in the judgment of the investigator, would interfere with the study
  • Pregnancy or breastfeeding, or plans to become pregnant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00301184

Locations
United States, Alabama
Alabama Vaccine CRS
Birmingham, Alabama, United States, 35294-2041
United States, Maryland
Project Brave HIV Vaccine CRS
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Brigham and Women's Hosp. CRS
Boston, Massachusetts, United States, 02115
United States, Missouri
Saint Louis Univ. School of Medicine, HVTU
St Louis, Missouri, United States, 63110-2500
United States, New York
Univ. of Rochester HVTN CRS
Rochester, New York, United States, 14642-0001
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
HIV Vaccine Trials Network
Investigators
Study Chair: Paul Goepfert, MD University of Alabama at Birmingham
Study Chair: Christine Mhorag Hay, MD 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: NCT00301184     History of Changes
Other Study ID Numbers: HVTN 065, 10140, 5-P01-AI049364-05
Study First Received: March 8, 2006
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
HIV Preventive Vaccine
HIV DNA Vaccine
Modified Vaccinia Ankara Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Vaccinia
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
Poxviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on April 17, 2014