Safety of and Immune Response to Two HIV Vaccine Formulations (rMVA-HIV and rFPV-HIV) Alone or in Combination in HIV Uninfected Adults

A Phase I Trial to Evaluate the Safety and Immunogenicity of rMVA-HIV (rMVA-HIV Env/Gag + rMVA-HIV Tat/Rev/Nef-RT) and rFPV-HIV (rFPV-HIV Env/Gag + rFPV-HIV Tat/Rev/Nef-RT) Vaccines, Alone or in Combination, in Healthy, Vaccinia Naive HIV-1 Negative Participants

The purpose of this study is to evaluate the safety of and immune response to two HIV vaccine formulations, rMVA-HIV and rFPV-HIV, alone and in combination, in HIV uninfected adults.

Study Overview

Detailed Description

Pox viruses are used for investigational vaccines in humans because they can accommodate large amounts of foreign DNA, can infect mammalian cells, and can access the cytotoxic T-cell responses believed to be important in the control of HIV infection and disease. Two pairs of matching recombinant HIV vaccines have been developed for use in this study. One pair uses a modified vaccinia Ankara (MVA) vector and the other pair uses a fowlpox vector (FPV). Each vaccine pair consists of one vaccine containing env/gag sequences and one vaccine containing modified tat/rev/nef-RT sequences. The HIV sequences are identical and are from a vertically transmitted pediatric primary isolate. The controls in this study are MVA vectors and FPVs without the HIV genes. The study will evaluate the safety and immunogenicity of the vaccine pairs.

There are two parts to this study. Participants in Part A will be randomly assigned to one of five different vaccination groups. Within each group, participants will be randomly assigned to receive either vaccine or control injections. Group 1 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Groups 2, 3, and 4 will receive one of three different doses of the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 5 participants will receive the MVA vaccine pair or MVA control at maximum tolerated dose (MTD) at each vaccine visit. Groups 1 and 2 will enroll simultaneously; Groups 3, 4, and 5 will enroll as safety data from the previous groups become available.

In Part B, participants will be randomly assigned to receive study vaccine or control vaccine in one of three vaccination groups. Group 6 participants will receive the FPV vaccine pair or FPV control at each vaccine visit. Group 7 participants will receive the MVA vaccine pair or MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 8 participants will receive the MVA vaccine pair at MTD or MVA control at each vaccine visit. Enrollment into Groups 6, 7, and 8 will begin simultaneously after the completion of the safety data evaluation of Groups 1 and 2.

Study vaccinations will be given at study entry and at Months 1, 3, 5 and 7. Tests for cardiac injury will be performed at screening and at each 2-week follow-up visit after vaccination. Participants will have an electrocardiogram (ECG) at screening and 2 weeks after the first and last vaccinations. Study visits will occur at screening, study entry, and at 11 visits over 13 months. Study visits will consist of a physical exam, risk reduction/pregnancy prevention counseling, cardiac symptom assessment, and blood and urine collection. Women will have pregnancy tests at study entry and Months 1, 3, 5, 7, and 13.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • 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

      • Rio de Janeiro, Brazil
        • Projeto Praca Onze/Hesfa Crs
      • San Paulo, Brazil
        • Sao Paulo HVTU - CRT DST/AIDS CRS
    • Alabama
      • Birmingham, Alabama, United States, 35294-2041
        • Alabama Vaccine CRS
    • Missouri
      • Saint Louis, Missouri, United States, 63110-2500
        • Saint Louis Univ. School of Medicine, HVTU
    • New York
      • Rochester, New York, United States, 14642
        • Univ. of Rochester HVTN CRS
    • Washington
      • Seattle, Washington, United States, 98104
        • FHCRC/UW Vaccine CRS

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

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Note: As of 11/29/06, vaccinations in this trial have been discontinued.

Inclusion Criteria:

  • HIV uninfected within 8 weeks prior to first vaccination
  • Blood pressure 140/90 or less upon enrollment
  • Good general health
  • Willing to receive HIV test results
  • Understand the vaccination procedure
  • Negative for hepatitis B surface antigen
  • Negative for anti-hepatitis C virus antibodies (anti-HCV) or negative for HCV PCR if anti-HCV is positive
  • Willing to use acceptable forms of contraception
  • Willing to be followed for the duration of the study
  • Have access to a participating HIV vaccine trial site

Exclusion Criteria:

  • HIV vaccines or placebos in prior HIV vaccine trial
  • Previously received Avipox vaccine
  • Previously received Vaccinia vaccine
  • 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 prophylaxis or therapy
  • Hypersensitivity to egg products
  • Past or present cardiac disease
  • Two or more of the following cardiac risk factors: history of fasting LDL greater than 160 mg/dl; first degree relative who had heart condition, excluding hypertension; cigarette smoking
  • ECG with clinically significant findings (e.g., conduction disturbance, repolarization abnormality, significant atrial or ventricular arrhythmia, frequent atrial or ventricular ectopy, ST elevation consistent with ischemia, evidence of past or evolving myocardial infarction)
  • Serious adverse reaction to vaccines. 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 2
  • Thyroid disease requiring treatment
  • Serious angioedema within the last 3 years
  • Bleeding disorder
  • Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
  • Seizure disorder requiring medication within the past 3 years
  • Absence of the spleen
  • Mental illness that would interfere with the study
  • Other conditions that, in the judgment of the investigator, would interfere with the study
  • Pregnancy or breastfeeding

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: FACTORIAL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1
rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
PLACEBO_COMPARATOR: 2
Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
EXPERIMENTAL: 3
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 4
Empty TBC-MVA vector administered in each deltoid on Days 0, 28; empty TBC-FPV vector administered in each deltoid on Days 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid
EXPERIMENTAL: 5
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 6
Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid
EXPERIMENTAL: 7
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 8
Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid
EXPERIMENTAL: 9
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 10
Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid
EXPERIMENTAL: 11
rFPV-HIV vaccine administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
PLACEBO_COMPARATOR: 12
Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
EXPERIMENTAL: 13
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28; rFPV-HIV env/gag and rFPV-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid at Days 84, 140, and 196
Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 14
Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196
Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid
EXPERIMENTAL: 15
rMVA-HIV env/gag and rMVA-HIV tat/rev/nef-RT administered as two separate 1-mL intramuscular injections, with rMVA-HIV env/gag into the left deltoid, rMVA-HIV tat/rev/nef-RT into the right deltoid at Days 0, 28, 84, 140, 196
rMVA 10^7 pfu /2mL administered in each deltoid
rMVA 10^8 pfu /2mL administered in each deltoid
rMVA 10^9 pfu /2mL administered in each deltoid
PLACEBO_COMPARATOR: 16
Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196
Empty MVA 10^7 pfu/2mL administered into each deltoid
Empty MVA 10^8 pfu/2mL administered into each deltoid
Empty MVA 10^9 pfu/2mL administered into each deltoid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events
Time Frame: After each injection and 12 months after the first injection
After each injection and 12 months after the first injection
Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses
Time Frame: At Days 98 and 210
At Days 98 and 210

Collaborators and Investigators

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

Investigators

  • Study Chair: Sharon Frey, MD, St. Louis University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2004

Study Completion (ACTUAL)

August 1, 2007

Study Registration Dates

First Submitted

May 26, 2004

First Submitted That Met QC Criteria

May 26, 2004

First Posted (ESTIMATE)

May 27, 2004

Study Record Updates

Last Update Posted (ACTUAL)

October 14, 2021

Last Update Submitted That Met QC Criteria

October 13, 2021

Last Verified

October 1, 2021

More Information

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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