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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00083603

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) Biological: Empty TBC-FPV Biological: TBC-MVA and TBC-FPV	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Factorial Assignment, Safety Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

U.S. FDA Resources

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

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses [ Time Frame: At Days 98 and 210 ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	July 2004
Estimated Study Completion Date:	November 2006
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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	Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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
2: Placebo Comparator Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
3: Experimental 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	Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^7 pfu /2mL administered in each deltoid Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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
4: Placebo Comparator 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	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid. Biological: TBC-MVA and TBC-FPV Empty MVA 10^7 pfu/2mL administered into each deltoid
5: Experimental 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	Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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 Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^8 pfu /2mL administered in each deltoid
6: Placebo Comparator Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid. Biological: TBC-MVA and TBC-FPV Empty MVA 10^8 pfu/2mL administered into each deltoid
7: Experimental 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	Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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 Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^9 pfu /2mL administered in each deltoid
8: Placebo Comparator Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid. Biological: TBC-MVA and TBC-FPV Empty MVA 10^9 pfu/2mL administered into each deltoid
9: Experimental 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	Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^9 pfu /2mL administered in each deltoid
10: Placebo Comparator Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196	Biological: TBC-MVA and TBC-FPV Empty MVA 10^9 pfu/2mL administered into each deltoid
11: Experimental 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	Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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
12: Placebo Comparator Empty TBC-FPV vector administered as two separate 1-mL intramuscular injections, one into each deltoid at Days 0, 28, 84, 140, and 196	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
13: Experimental 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	Biological: rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT) 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 Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^9 pfu /2mL administered in each deltoid
14: Placebo Comparator Empty TBC-MVA vector administered in each deltoid Days 0, 28; empty TBC-FPV vector administered in each deltoid Days 84, 140, and 196	Biological: Empty TBC-FPV Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid. Biological: TBC-MVA and TBC-FPV Empty MVA 10^9 pfu/2mL administered into each deltoid
15: Experimental 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	Biological: rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT) rMVA 10^9 pfu /2mL administered in each deltoid
16: Placebo Comparator Empty TBC-MVA vector administered in each deltoid Days 0, 28, 84, 140, 196	Biological: TBC-MVA and TBC-FPV Empty MVA 10^9 pfu/2mL administered into each deltoid

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.

Eligibility

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

Criteria

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

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-2041
United States, Massachusetts
Harvard Medical School/Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis University - New Hope Bldg
St. Louis, Missouri, United States, 63110-2500
United States, New York
New York Blood Center - Bronx
Bronx, New York, United States, 10456
United States, Rhode Island
Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Washington
FHCRC/UW - Vaccine Trials Unit
Seattle, Washington, United States, 98104
Brazil
Hospital Escola Sao Francisco de Assis (HESFA)
Cidade Nova, Brazil, 20210-303
Centro de Referencia e Treinamento-DST/AIDS
San Paulo, Brazil

Study Chair:	Michael Keefer, MD	University of Rochester
Study Chair:	Sharon Frey, MD	St. Louis University School of Medicine

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	HVTN 055
Study First Received:	May 26, 2004
Last Updated:	August 26, 2009
ClinicalTrials.gov Identifier:	NCT00083603 History of Changes
Health Authority:	United States: Food and Drug Administration