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Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), May 2009
First Received: January 8, 2009   Last Updated: November 4, 2009   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00820846
  Purpose

The purpose of this study is to evaluate the safety of and immune response to a two vaccine regimen in healthy, HIV-uninfected adults who never received an HIV preventive vaccine before.


Condition Intervention Phase
HIV Infections
Biological: Vaccine
Biological: Placebo
Phase II

Study Type: Interventional
Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase 2a Clinical Trial to Evaluate the Safety and Immunogenicity of a Prime-boost Vaccine Regimen of pGA2/JS7 DNA and MVA/HIV62, in Health, HIV Uninfected Vaccinia-naive Adult Participants

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Frequency of severe local and systemic reactogenicity signs and symptoms [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Frequency of adverse events and assessed relationship to study products [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Laboratory measures of safety: boxplots of WBC, neutrophils, lymphocytes, hemoglobin, platelets, ALT, creatinine, and cardiac troponin results at baseline and following vaccination [ Time Frame: At study entry and following vaccinations ] [ Designated as safety issue: Yes ]
  • Number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequency of CD4+ T cell responses 2 weeks after the last MVA vaccination [ Time Frame: Following last MVA vaccination ] [ Designated as safety issue: No ]
  • Frequency of CD8+ T cell responses 2 weeks after last MVA vaccination [ Time Frame: 2 weeks following last MVA vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Responses to individual HIV PTE peptide pools representing ENV, Gag, and Pol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequencies of responding CD4+ and CD8+ T cells producing IFN-gamma, IL-2, TNF-alpha, CD57, perforin, granzyme B, or demonstrating other functions [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequency of humoral responses detected by HIV binding antibody assays to p55 Gag and gp140 Env [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Frequency of vaccine-induced positive results with end of study HIV serological testing by commercial assays [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 225
Study Start Date: January 2009
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
Participants will receive the JS7 DNA and MVA/HIV62 vaccinations
Biological: Vaccine
Administered as an intramuscular injection four times over the course of 6 months
B: Placebo Comparator
Participants will receive the placebo equivalents of the JS7 DNA and MVA/HIV62 vaccines
Biological: Placebo
Administered as an intramuscular injection four times over the course of 6 months

Detailed Description:

Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not able to achieve their desired response. An alternative strategy to the antibody approach is the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were previously demonstrated to play an important role in the control of simian immunodeficiency virus (SIV), the HIV equivalent seen in rhesus macaque monkeys. Additionally, other studies suggest CTLs play an important role in viral control during chronic infection. Based on this information, several groups have shifted their focus to the development of CTL-based vaccines, some of which have entered advanced clinical trials.

A DNA/rMVA vaccine strategy is structured to bring about both T cell and antibody responses. The primary vaccination is DNA based and will express only HIV proteins as a way to produce an HIV-focused immune response. A secondary, rMVA boost vaccination, which expresses both HIV and MVA proteins will ideally amplify the focused response of the initial vaccination. The DNA and rMVA are physically two different vaccinations given at separate times but together they make up one preventive regimen. Both vaccine components express non-infectious virus-like particles.

This study is a multicenter, randomized study, which is comprised of both vaccine and placebo recipients. Each vaccine is given twice, for a total of four injections over 6 months. The study will last for a total of 12 months for participants, including enrollment and follow-up.

  Eligibility

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

Inclusion Criteria:

  • Access to a participating HVTN clinical research center and willing to be followed for the planned duration of the study
  • Ability and willingness to provide informed consent
  • Assessment of understanding: completion of a questionnaire prior to first vaccination; demonstration of understanding for all questionnaire items answered incorrectly
  • Willingness to receive HIV test results
  • Good general health as shown by medical history , physical exam, and screening laboratory tests
  • Certain specified laboratory values. More information on this criterion can be found in the study protocol.
  • If pregnancy is possible, must agree to use contraception from at least 21 days prior to enrollment through the last protocol visit for sexual activity that could lead to pregnancy. More information on this criterion can be found in the study protocol.
  • Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit, and willing to continue annual follow-up contact after the last required protocol clinic visit, for a total of 5 years following enrollment
  • Assessed by clinic staff as being at "low risk" for HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment. More information on this criterion can be found in the study protocol.

Exclusion Criteria:

  • HIV vaccine(s) received in a prior HIV vaccine trial. If placebo received during previous trial, eligibility will be determined on a case-by-case basis. Exceptions may be made for vaccines that have undergone licensure. More information on this criterion can be found in the study protocol.
  • Receipt of smallpox vaccination
  • Excessive alcohol use or frequent binge drinking or chronic marijuana abuse or any other use of illicit drugs, such as cocaine or methamphetamine, within the past 12 months
  • History of newly acquired or newly diagnosed syphilis; a history of newly acquired gonorrhea, nongonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia,pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis,epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B, within the past 12 months
  • Immunosuppressive medication received within 168 fays before first vaccination. Certain medications are excluded from this criterion, more information can be found in the study protocol.
  • Blood products received within 120 days before first vaccination
  • Immunoglobulin received within 60 days before first vaccination
  • Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection
  • Any vaccines that are not live attenuated and were received within 14 days prior to first vaccination or that are scheduled within 14 days after injection
  • Injected research agents received within 30 days before first vaccination
  • Intent to participate in another study of an investigational research agent during the planned duration of this study
  • Current anti-tuberculosis (TB) prophylaxis or therapy
  • Clinically significant medical condition. More information on this criterion can be found in the study protocol.
  • Any medical, psychiatric, or social condition, or occupational or other responsibility that in the opinion of the investigator might interfere with the study protocol
  • Serious adverse reactions to vaccines. More information on this criterion can be found in the study protocol.
  • Allergy to eggs and/or egg products
  • History of, or known active cardiac disease. More information on this criterion can be found in the study protocol.
  • Participants who have 2 or more of the following cardiac risk factors: (1) participant report of history of elevated blood cholesterol defined as fasting LDL greater than 160 mg/dL; (2) first degree relative (for example, mother, father, sister, or brother) who had coronary artery disease before the age of 50 years; (3) current smoker; or (4) body mass index greater than or equal to 35.
  • ECG with clinically significant findings. More information on this criterion can be found in the study protocol.
  • Autoimmune disease
  • Immunodeficiency
  • Asthma other than mild, well-controlled asthma. More information on this criterion can be found in the study protocol.
  • Diabetes mellitus, type 1 or type 2, including cases controlled with diet alone. Those with a history of isolated gestational diabetes are not excluded.
  • Thyroidectomy, or thyroid disease requiring medication during the last 12 months
  • Angioedema within the last 3 years if episodes are considered serious or have required medication within the last 2 years
  • Hypertension. More information on this criterion can be found in the study protocol.
  • Body mass index greater than or equal to 40
  • Bleeding disorder diagnosed by a doctor
  • Malignancy. Participants with surgical excisions and subsequent observation periods, that in the investigator's estimation has a reasonable assurance of sustained cure or is unlikely to recur during the period of study, are not excluded.
  • Seizure disorder, unless the participant has not required medication or had a seizure within the last 3 years.
  • Asplenia
  • Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture with the past 3 years.
  • Pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00820846

Locations
United States, Alabama
Alabama Vaccine CRS Recruiting
Birmingham, Alabama, United States, 35294-2050
Contact: Susan F. Duncan, CRNP, MSN     205-975-2840     sduncan@uab.edu    
Principal Investigator: Paul A. Goepfert, MD            
United States, Massachusetts
Brigham and Women's Hosp. CRS Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Lizanne C. Noble, MPH     617-732-5394     lnoble@partners.org    
Principal Investigator: Lindsey R. Baden, MD            
Fenway Community Health Clinical Research Site (FCHCRS) Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Marie Feldmannova     617-927-6075     Mfeldmannova@fenwayhealth.org    
Principal Investigator: Kenneth H. Mayer, MD            
United States, New York
Univ. of Rochester HVTN CRS Recruiting
Rochester, New York, United States, 14642-0001
Contact: Catherine A. Bunce, RN, MS, CCRC     585-275-5744     catherine_bunce@urmc.rochester.edu    
Principal Investigator: Michael C. Keefer, MD            
HIV Prevention & Treatment CRS Not yet recruiting
New York, New York, United States, 10032
Contact: Steven Chang     212-305-1570     sc1286@columbia.edu    
Principal Investigator: Scott M. Hammer, MD            
NY Blood Ctr./Bronx CRS Recruiting
Bronx, New York, United States, 10455
Contact: Debbie Lucy     718-402-0743 ext 309     dlucy@nybloodcenter.org    
Principal Investigator: Beryl Koblin, PhD            
NY Blood Ctr./Union Square CRS Recruiting
New York, New York, United States, 10003
Contact: Krista Goodman     212-388-0008 ext 20     kgoodman@nybloodcenter.org    
Principal Investigator: Beryl Koblin, PhD            
United States, Tennessee
Vanderbilt Vaccine CRS Recruiting
Nashville, Tennessee, United States, 37232-2222
Contact: Kyle Rybzyk     615-322-5641     kyle.rybczyk@vanderbilt.edu    
Principal Investigator: Spyros A. Kalams, MD            
Peru, Maynas
Asociacion Civil Selva Amazonica, CRS Recruiting
Iquitos, Maynas, Peru
Contact: Lilian Saavedra Sevillano     51-6-5236277 ext 107     lsaavedra@acsaperu.org    
South Africa
CAPRISA eThekwini CRS Not yet recruiting
Durban, South Africa, 4011
Contact: Munira Khan     27-031-260 1918     gengiahs@ukzn.ac.za    
Principal Investigator: Nesri Padayatchi, MD            
Sponsors and Collaborators
Investigators
Study Chair: Paul A Goepfert, M.D. UAB, Div. of Infectious Diseases
  More Information

Additional Information:
Publications:
Responsible Party: DAIDS ( Rona Siskind )
Study ID Numbers: HVTN 205
Study First Received: January 8, 2009
Last Updated: November 4, 2009
ClinicalTrials.gov Identifier: NCT00820846     History of Changes
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 08, 2010