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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
pGA2/JS7 DNA vaccine
Placebo
MVA/HIV62 vaccine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV Seronegativity, HIV Preventive Vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Alabama CRS
  • Bridge HIV CRS
  • The Hope Clinic of the Emory Vaccine Center CRS
  • Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
  • Fenway Health (FH) CRS
  • Columbia P&S CRS
  • New York Blood Center CRS
  • University of Rochester Vaccines to Prevent HIV Infection CRS
  • Vanderbilt Vaccine (VV) CRS
  • Seattle Vaccine and Prevention CRS
  • ACSA CRS
  • Barranco CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Placebo Comparator

Arm Label

Part A, Group 1

Part A, Group 2

Part B, Group 3

Part B, Group 4

Part B, Group 5

Arm Description

Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine

Participants will receive four placebo injections

Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine

Participants will receive three injections of the MVA/HIV62 vaccine and one injection of the placebo

Participants will receive four placebo injections

Outcomes

Primary Outcome Measures

Frequency of severe local and systemic reactogenicity signs and symptoms
Frequency of adverse events and assessed relationship to study products
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
Number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation

Secondary Outcome Measures

Responses to individual HIV potential T-cell epitope (PTE) peptide pools representing Env, Gag, and Pol
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
Frequency and titer of humoral responses detected by HIV binding antibody assays to p55 Gag and gp140 Env
Frequency of vaccine-induced positive results with end of study HIV serological testing by commercial assays
Frequency of CD4+ T-cell responses
Frequency of CD8+ T-cell responses

Full Information

First Posted
January 8, 2009
Last Updated
August 4, 2022
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00820846
Brief Title
Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV Seronegativity, HIV Preventive Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
299 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A, Group 1
Arm Type
Experimental
Arm Description
Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Arm Title
Part A, Group 2
Arm Type
Placebo Comparator
Arm Description
Participants will receive four placebo injections
Arm Title
Part B, Group 3
Arm Type
Experimental
Arm Description
Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Arm Title
Part B, Group 4
Arm Type
Experimental
Arm Description
Participants will receive three injections of the MVA/HIV62 vaccine and one injection of the placebo
Arm Title
Part B, Group 5
Arm Type
Placebo Comparator
Arm Description
Participants will receive four placebo injections
Intervention Type
Biological
Intervention Name(s)
pGA2/JS7 DNA vaccine
Intervention Description
1 mL of pGA2/JS7 DNA vaccine
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
1 mL of sodium chloride for injection
Intervention Type
Biological
Intervention Name(s)
MVA/HIV62 vaccine
Intervention Description
1 mL of recombinant modified vaccinia Ankara/HIV clade B gag-pol-env (MVA/HIV62)
Primary Outcome Measure Information:
Title
Frequency of severe local and systemic reactogenicity signs and symptoms
Time Frame
Throughout study
Title
Frequency of adverse events and assessed relationship to study products
Time Frame
Throughout study
Title
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
Title
Number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation
Time Frame
Throughout study
Secondary Outcome Measure Information:
Title
Responses to individual HIV potential T-cell epitope (PTE) peptide pools representing Env, Gag, and Pol
Time Frame
Throughout study
Title
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
Title
Frequency and titer of humoral responses detected by HIV binding antibody assays to p55 Gag and gp140 Env
Time Frame
Measured at study completion
Title
Frequency of vaccine-induced positive results with end of study HIV serological testing by commercial assays
Time Frame
Measured at study completion
Title
Frequency of CD4+ T-cell responses
Time Frame
Measured 2 weeks following last MVA vaccination
Title
Frequency of CD8+ T-cell responses
Time Frame
Measured 2 weeks following last MVA vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul A Goepfert, MD
Organizational Affiliation
UAB, Div. of Infectious Diseases
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Bridge HIV CRS
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
The Hope Clinic of the Emory Vaccine Center CRS
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115-6110
Country
United States
Facility Name
Fenway Health (FH) CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215-4302
Country
United States
Facility Name
Columbia P&S CRS
City
New York
State/Province
New York
ZIP/Postal Code
10032-3732
Country
United States
Facility Name
New York Blood Center CRS
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester Vaccines to Prevent HIV Infection CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Vanderbilt Vaccine (VV) CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2582
Country
United States
Facility Name
Seattle Vaccine and Prevention CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
ACSA CRS
City
Iquitos
State/Province
Maynas
ZIP/Postal Code
1
Country
Peru
Facility Name
Barranco CRS
City
Lima
ZIP/Postal Code
04
Country
Peru

12. IPD Sharing Statement

Citations:
PubMed Identifier
18753857
Citation
Miedema F. A brief history of HIV vaccine research: stepping back to the drawing board? AIDS. 2008 Sep 12;22(14):1699-703. doi: 10.1097/QAD.0b013e3283021a61.
Results Reference
background
PubMed Identifier
16847401
Citation
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. doi: 10.1097/01.aids.0000237362.26370.f8. No abstract available.
Results Reference
background
PubMed Identifier
24403557
Citation
Goepfert PA, Elizaga ML, Seaton K, Tomaras GD, Montefiori DC, Sato A, Hural J, DeRosa SC, Kalams SA, McElrath MJ, Keefer MC, Baden LR, Lama JR, Sanchez J, Mulligan MJ, Buchbinder SP, Hammer SM, Koblin BA, Pensiero M, Butler C, Moss B, Robinson HL; HVTN 205 Study Group; National Institutes of Allergy and Infectious Diseases HIV Vaccines Trials Network. Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2014 Jul 1;210(1):99-110. doi: 10.1093/infdis/jiu003. Epub 2014 Jan 7.
Results Reference
background
PubMed Identifier
28131393
Citation
Huang Y, Zhang L, Janes H, Frahm N, Isaacs A, Kim JH, Montefiori D, McElrath MJ, Tomaras GD, Gilbert PB. Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials. Vaccine. 2017 Feb 22;35(8):1184-1193. doi: 10.1016/j.vaccine.2016.09.053. Epub 2017 Jan 25.
Results Reference
derived

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

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