Trial record 6 of 28 for:    " December 24, 2008":" January 23, 2009"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00820846
First received: January 8, 2009
Last updated: May 27, 2014
Last verified: May 2014
  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 have never received an HIV preventive vaccine before.


Condition Intervention Phase
HIV Infections
Biological: DNA Vaccine
Biological: Placebo
Biological: rMVA vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
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 Healthy, 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, including boxplots of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (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 ]

Secondary Outcome Measures:
  • Responses to individual HIV potential T-cell epitope (PTE) peptide pools representing Env, Gag, and Pol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Percentage of responding CD4+ and CD8+ T cells producing interferon (IFN)-gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, CD57, perforin, or granzyme B or demonstrating other functions [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Frequency and titer of humoral responses detected by HIV binding antibody assays to p55 Gag and gp140 Env [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Frequency of vaccine-induced positive results with end of study HIV serological testing by commercial assays [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Frequency of CD4+ T-cell responses [ Time Frame: Measured 2 weeks following last MVA vaccination ] [ Designated as safety issue: No ]
  • Frequency of CD8+ T-cell responses [ Time Frame: Measured 2 weeks following last MVA vaccination ] [ Designated as safety issue: No ]

Enrollment: 299
Study Start Date: January 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A, Group 1
Participants will receive two injections of the JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Biological: DNA Vaccine
1 mL of pGA2/JS7 DNA vaccine
Biological: rMVA vaccine
1 mL of recombinant modified vaccinia Ankara/HIV clade B gag-pol-env (MVA/HIV62)
Placebo Comparator: Part A, Group 2
Participants will receive four placebo injections
Biological: Placebo
1 mL of sodium chloride for injection
Experimental: Part B, Group 3
Participants will receive two injections of the JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Biological: DNA Vaccine
1 mL of pGA2/JS7 DNA vaccine
Biological: rMVA vaccine
1 mL of recombinant modified vaccinia Ankara/HIV clade B gag-pol-env (MVA/HIV62)
Experimental: Part B, Group 4
Participants will receive three injections of the MVA/HIV62 vaccine and one injection of the placebo
Biological: Placebo
1 mL of sodium chloride for injection
Biological: rMVA vaccine
1 mL of recombinant modified vaccinia Ankara/HIV clade B gag-pol-env (MVA/HIV62)
Placebo Comparator: Part B, Group 5
Participants will receive four placebo injections
Biological: Placebo
1 mL of sodium chloride for injection

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. An rMVA vaccine strategy expresses both HIV and MVA proteins and may amplify the focused response of a DNA vaccination. Participants in this study will receive either a combined DNA/rMVA vaccine strategy, in which they receive both types of vaccines; an rMVA vaccine strategy, in which they receive only the rMVA vaccine; or a placebo. The DNA and rMVA are physically two different vaccinations given at separate times, but in the DNA/rMVA group, they will be used together to make up one preventive regimen. Both vaccine components express noninfectious virus-like particles.

This study is a multicenter, randomized study that is conducted in two parts and comprised of five groups. In all groups, participants will receive four injections. In Part A, Groups 1 and 2 will be compared. In Group 1, participants will receive two shots of the DNA vaccine and two shots of the rMVA vaccine. In Group 2, participants will receive four placebo injections. In Part B, Groups 3, 4, and 5 will be compared. In Group 3, the combination vaccine strategy will be used again; in Group 4, a single-vaccine strategy of three injections of the rMVA vaccine and one injection of placebo will be given; and in Group 5, participants will again receive four placebo injections. 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 HIV Vaccine Trials Network (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" of 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) or other experimental vaccines, received in a prior HIV vaccine trial. More information on this criterion can be found in the study protocol.
  • Receipt of smallpox vaccination
  • Excessive alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs, such as cocaine or methamphetamine, within the past 12 months
  • History of newly acquired or newly diagnosed syphilis; 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 days 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 other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection
  • Influenza vaccine or 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
  • Allergy treatment with antigen injections within 30 days before first vaccination or scheduled within 14 days after injection
  • 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 two or more of the following cardiac risk factors: (1) participant report of history of elevated blood cholesterol defined as fasting low-density lipoprotein (LDL) greater than 160 mg/dL; (2) first degree relative (e.g., 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.
  • Electrocardiogram (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 have a reasonable assurance of sustained cure or are 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
  • Pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820846

Locations
United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
Bridge HIV CRS
San Francisco, California, United States, 94143
United States, Georgia
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States, 30030
United States, Massachusetts
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States, 02115-6110
Fenway Health (FH) CRS
Boston, Massachusetts, United States, 02215-4302
United States, New York
Columbia P&S CRS
New York, New York, United States, 10032-3732
New York Blood Center CRS
New York, New York, United States, 10065
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, United States, 37232-2582
United States, Washington
Seattle Vaccine and Prevention CRS
Seattle, Washington, United States, 98109-1024
Peru
ACSA CRS
Iquitos, Maynas, Peru, 1
Barranco CRS
Lima, Peru, 04
Sponsors and Collaborators
Investigators
Study Chair: Paul A Goepfert, MD UAB, Div. of Infectious Diseases
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00820846     History of Changes
Other Study ID Numbers: HVTN 205, 10658
Study First Received: January 8, 2009
Last Updated: May 27, 2014
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:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 28, 2014