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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):	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 have never received an HIV preventive vaccine before.

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

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

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 ]

Estimated Enrollment:	300
Study Start Date:	January 2009
Estimated Primary Completion Date:	March 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

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

Locations

United States, Alabama
Alabama Vaccine CRS
Birmingham, Alabama, United States, 35294-2050
United States, California
San Francisco Vaccine and Prevention CRS
San Francisco, California, United States, 94102-6033
United States, Georgia
Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States, 30030
United States, Massachusetts
Brigham and Women's Hosp. CRS
Boston, Massachusetts, United States, 02115
Fenway Community Health Clinical Research Site (FCHCRS)
Boston, Massachusetts, United States, 02115
United States, New York
NY Blood Ctr./Bronx CRS
Bronx, New York, United States, 10455
HIV Prevention & Treatment CRS
New York, New York, United States, 10032
NY Blood Ctr./Union Square CRS
New York, New York, United States, 10003
Univ. of Rochester HVTN CRS
Rochester, New York, United States, 14642-0001
United States, Tennessee
Vanderbilt Vaccine CRS
Nashville, Tennessee, United States, 37232-2222
United States, Washington
FHCRC/UW Vaccine CRS
Seattle, Washington, United States, 98104
Peru
Asociacion Civil Selva Amazonica, CRS
Iquitos, Maynas, Peru
Barranco CRS
Lima, Peru, 04
South Africa
CAPRISA eThekwini CRS
Durban, South Africa, 4011

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Paul A Goepfert, MD

UAB, Div. of Infectious Diseases

More Information

Additional Information:

Click here for more information about preventive HIV vaccines This link exits the ClinicalTrials.gov site

Publications:

Miedema F. A brief history of HIV vaccine research: stepping back to the drawing board? AIDS. 2008 Sep 12;22(14):1699-703. Review.

Rerks-Ngarm S, Brown AE, Khamboonruang C, Thongcharoen P, Kunasol P. HIV/AIDS preventive vaccine 'prime-boost' phase III trial: foundations and initial lessons learned from Thailand. AIDS. 2006 Jul 13;20(11):1471-9. Review. No abstract available.

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:	January 3, 2012
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 February 09, 2012