Safety of and Immune Response to Polyvalent HIV-1 Vaccine in HIV Uninfected Adults

September 25, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Multi-Gene, Polyvalent HIV-1 DNA Plasmid Prime/Env Protein Boost Vaccine Formulation, DP6-001 in Healthy Volunteers

This study will evaluate the safety of and immune response to a new HIV vaccine. The vaccine in this trial uses pieces of HIV DNA and HIV proteins. The vaccine itself cannot cause HIV infection or AIDS.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Unlike other viruses for which effective vaccines have been developed, HIV-1 has evolved mechanisms to evade immune control over virus replication. These mechanisms include the extraordinary genetic diversity of the virus, viral latency, and targeting of the immune system. Evolutional variations of the envelope gene have not only resulted in the development of different groups (M, N, and O) and subgroups (clades) in diverse geographic regions of the world, but also significant genomic variations within clades. These clade variants of HIV will require novel vaccine approaches to elicit population-based protective immunity. Viral latency is the ability of the virus to remain dormant for long periods through integrating its viral DNA into the host genome. Viral latency requires vaccines to produce immune response that are robust enough to kill the virus and that can be maintained over extended periods of time to produce lasting immunity. Finally, HIV-1 targets CD4 cells and thus compromises the immune surveillance mechanisms critical to maintaining both cellular and humoral immunity to HIV-1. Therefore, an effective vaccine against HIV-1 must bolster the development of broadly reactive neutralizing antibodies against genetic variants of HIV-1, as well as induce an effective HIV-specific CTL response to eliminate virus-infected cells. The ideal vaccine approach will produce long-term responses within these arms of host immunity. This study is designed to evaluate the safety, tolerability, and immunogenicity of a novel prophylactic vaccine consisting of DNA priming followed by a protein boost.

The first vaccine component administered in this study is a DNA vaccination; the second component is a recombinant protein vaccination. This combination will be used to determine whether the vaccine strategy can induce a balanced humoral and cell mediated immune responses to HIV-1.

Two HIV antigens, Gag and Env, are included in this study's vaccine formulation. Studies have shown that HIV-1 Gag is a potent inducer of cell mediated immune responses, while Env is the target of neutralizing antibody responses. The vaccine used in this study contains a 5-valent Env design (Env derived from one of 5 clades of HIV) in order to examine if a polyvalent Env formulation may expand the breadth of neutralizing antibody responses induced in human volunteers. For both DNA priming and protein boosting, a set of Env antigens from clades A, B, C, and E of HIV-1 M group will be produced (2 Env antigens from clade B and 1 Env each from the other three clades). All 5 Env antigens are selected from the primary HIV-1 viral isolates with the hope of producing broad antibody responses against the primary viruses circulating in the worldwide human population.

Thirty-six healthy volunteers will be randomized to one of five groups. Groups 1, 2, and 3 will receive different doses of the vaccine to determine the optimal dose. Groups 4 and 5 will receive the vaccine through either intradermal or intramuscular administration. Each group will receive 3 doses of DNA vaccination at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28. Blood sampling throughout the duration of the study will provide an assessment of the safety and immunogenicity of the vaccine in healthy volunteers. It is expected that volunteers will be enrolled in this study for 1 year.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria

  • HIV uninfected
  • Good general health as determined by medical history, physical examination, vital signs, and clinical laboratory measurements
  • Body Mass Index (BMI) =< 32
  • Hepatitis B surface antigen negative
  • Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive
  • Low risk for HIV exposure
  • No co-existent endocrine conditions
  • No evidence of hepatic insufficiency, significant renal insufficiency, or proteinuria
  • Acceptable methods of contraception
  • Anticipated availability for the planned follow-up period of one year

Exclusion Criteria

  • Certain medications during the 2 weeks prior to study entry
  • Donation of a unit of blood within 2 months prior to study entry
  • Participation in a study of investigational or marketed drugs within 1 month prior to study entry
  • Blood transfusion within 6 months prior to study entry
  • Pregnant, breastfeeding, or planning pregnancy during the study period
  • History of significant adverse reaction to any vaccine
  • Prior receipt of any experimental HIV vaccine
  • Morbid obesity (> 195% of ideal body weight)
  • Hypertension (patients may be taking concomitant antihypertensive medication during the study if approved by study officials)
  • History of chronic medical illness, malignancy, or autoimmune disorder
  • History of immunodeficiency or treatment with immunosuppressive medications
  • History of organ transplant
  • Medical or psychiatric obstacle to compliance with protocol
  • Significant urine concentration of any drug that could interfere with the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
Participants will receive different doses of the vaccine to determine the optimal dose
Biological: HIV-1 DNA vaccine with protein vaccine boost
Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 2
Participants will receive different doses of the vaccine to determine the optimal dose
Biological: HIV-1 DNA vaccine with protein vaccine boost
Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 3
Participants will receive different doses of the vaccine to determine the optimal dose
Biological: HIV-1 DNA vaccine with protein vaccine boost
Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 4
Participants will receive the vaccine through either intradermal or intramuscular administration
Biological: HIV-1 DNA vaccine with protein vaccine boost
Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 5
Participants will receive the vaccine through either intradermal or intramuscular administration
Biological: HIV-1 DNA vaccine with protein vaccine boost
Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Safety and tolerability
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Cross-clade neutralizing antibody
Time Frame: Throughout study
Throughout study
Cellular immunity
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jeff Kennedy, MD, University of Massachusetts, Worcester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2005

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2003

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2003

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2003

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 26, 2008

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2008

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • N01AI05394
  • N01-AI05394

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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