Clinical trial NCT00083603: Safety of and Immune Response to Two HIV Vaccine Formulations (rMVA-HIV and rFPV-HIV) Alone or in Combination in HIV Uninfected Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Vaccinia vector
Pox vector
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2004-05-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events
timeFrame: After each injection and 12 months after the first injection
measure: Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses
timeFrame: At Days 98 and 210
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: Saint Louis
country: United States
facility: Saint Louis Univ. School of Medicine, HVTU
state: Missouri
city: Rochester
country: United States
facility: Univ. of Rochester HVTN CRS
state: New York
city: Seattle
country: United States
facility: FHCRC/UW Vaccine CRS
state: Washington
city: Rio de Janeiro
country: Brazil
facility: Projeto Praça Onze/Hesfa Crs
city: San Paulo
country: Brazil
facility: Sao Paulo HVTU - CRT DST/AIDS CRS
Study officials:
affiliation: University of Rochester
name: Michael Keefer, MD
role: STUDY_CHAIR
affiliation: St. Louis University School of Medicine
name: Sharon Frey, MD
role: STUDY_CHAIR
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