Evaluating the Safety and Immune Response of DNA/MVA Vaccines in HIV-1-Infected Young Adults Taking Anti-HIV Medications
A Phase 1 Study of the Safety and Immunogenicity of DNA/MVA Immunizations With Co-Expressed GM-CSF in HIV-1 Infected Young Adults With Suppressed Viremia on HAART
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
The purpose of this study is to evaluate the safety of two HIV vaccines in HIV-1-infected young adults who are taking anti-HIV medications and have very low virus levels. This study will also look at how the immune system responds to the vaccines.
Trial Health
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 24, 2013
CompletedFirst Posted
Study publicly available on registry
July 26, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedNovember 11, 2021
August 1, 2013
July 24, 2013
November 4, 2021
Conditions
Outcome Measures
Primary Outcomes (5)
Grade 3 or higher adverse events (AEs)
Measured through Week 120
Progression of HIV disease status: immunological decline
Immunological decline defined as a fall in CD4 T-cell count to fewer than 350 cells/mm\^3 OR a decline to a level less than 50 percent of baseline, if baseline CD4 T-cell count is more than 700 cells/mm\^3 at study entry
Measured through Week 120
Progression of HIV disease status: RNA 1,000 copies/mL or greater measured on two occasions at least 1 week apart
Measured through Week 120
Progression of HIV disease status: development of an AIDS-defining opportunistic infection or malignancy
Measured through Week 120
A greater than or equal to two-fold increase in the frequency of responding HIV-1 Gag-specific CD8 T cells between entry visit and Week 17 visit
Measured through Week 17
Secondary Outcomes (2)
Grade 3 or higher AEs at least possibly related to study treatment
Measured through Week 120
A greater than or equal to two-fold increase in the frequency of responding HIV-1 Gag-specific CD8 T cells per individual between entry visit and Week 25 visit
Measured through Week 25
Study Arms (2)
Arm A: GEO-D03 DNA and MVA/HIV62B vaccines
EXPERIMENTALAt study entry and Week 8, participants will receive the GEO-D03 DNA vaccine administered as 1 mL intramuscularly (IM) in either deltoid. At Weeks 16 and 24, they will receive the MVA/HIV62B vaccine administered as 1 mL IM in either deltoid.
Arm B: Placebo for GEO-D03 and MVA/HIV62B
PLACEBO COMPARATORAt study entry and Week 8, participants will receive the placebo for GEO-D03 DNA vaccine administered as 1 mL IM in either deltoid. At Weeks 16 and 24, they will receive the placebo for MVA/HIV62B vaccine administered as 1 mL IM in either deltoid.
Interventions
DNA GEO-D03 vaccine will be administered as a 3 mg dose IM.
MVA/HIV62B vaccine will be administered as a 1 x 10\^8 TCID50 dose IM.
Placebo for DNA GEO-D03 (administered as 0.9 percent Sodium Chloride for Injection) will be administered IM.
Placebo for MVA/HIV62B 1 x 10\^8 TCID50 (administered as 0.9 percent Sodium Chloride for Injection) will be administered IM.
Eligibility Criteria
You may qualify if:
- HIV-1 infected. More details on this criterion can be found in the protocol.
- Likely HIV-1 acquisition in North America or Europe (in the opinion of the site investigator)
- Likely HIV-1 acquisition from sexual transmission (in the opinion of the site investigator)
- On stable HAART, defined as at least three different antiretrovirals (ARVs) from two different classes, with plasma HIV-1 RNA levels fewer than 100 copies/mL for at least 12 months prior to screening. Furthermore, at least two plasma HIV-1 RNA levels fewer than 100 copies/mL (and none with plasma HIV-1 RNA levels 100 or more copies/mL), separated by at least 3 months must have been documented during the 6-month period prior to enrollment.
- Ability and willingness of participant to provide signed written informed consent
- CD4 count 400 cells/mm\^3 or greater at screening
- The following lab values (at screening visit):
- Creatine phosphokinase no higher than 5 times the upper limit of normal (ULN). More details on this criterion can be found in the protocol.
- Troponin I no more than 1.0 times ULN
- Hemoglobin greater than 10 g/dL
- Absolute neutrophil count greater than 1,000 mm\^3
- Platelets greater than 100,000 mm\^3
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no greater than 1.5 times ULN
- Total bilirubin no greater than 1.5 times ULN (less than 5 times ULN if taking atazanavir)
- Creatinine less than 2.0 mg/dL
- +4 more criteria
You may not qualify if:
- Documentation of infection with HIV-1 other than Clade B (e.g., if genotype data are available from pre-treatment viral resistance analyses)
- Documentation that the last CD4 T-cell count prior to the initiation of ARV was fewer than 300 cells/mm\^3
- Hepatitis B surface antigen positive
- Hepatitis C virus RNA positive
- History of or known active cardiac disease including:
- evidence of past or evolving myocardial infarction
- angina pectoris
- congestive heart failure with permanent sequelae
- cardiomyopathy (hypertrophic or dilated)
- myocarditis
- pericarditis
- clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up)
- stroke or transient ischemic attack
- anginal chest pain or shortness of breath with mild activity (such as walking upstairs) due to cardiac disease (New York Heart Association \[NYHA\] class 2-4)
- Screening ECG with clinically significant findings or features that would interfere with the assessment of myo/pericarditis, including any of the following:
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (3)
Rosenberg ES, Graham BS, Chan ES, Bosch RJ, Stocker V, Maenza J, Markowitz M, Little S, Sax PE, Collier AC, Nabel G, Saindon S, Flynn T, Kuritzkes D, Barouch DH; AIDS Clinical Trials Group A5187 Team. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection. PLoS One. 2010 May 10;5(5):e10555. doi: 10.1371/journal.pone.0010555.
PMID: 20479938BACKGROUNDPersaud D, Luzuriaga K, Ziemniak C, Muresan P, Greenough T, Fenton T, Blackford A, Ferguson K, Neu N, Cunningham CK. Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. AIDS. 2011 Nov 28;25(18):2227-34. doi: 10.1097/QAD.0b013e32834cdaba.
PMID: 21918423BACKGROUNDGoepfert PA, Elizaga ML, Sato A, Qin L, Cardinali M, Hay CM, Hural J, DeRosa SC, DeFawe OD, Tomaras GD, Montefiori DC, Xu Y, Lai L, Kalams SA, Baden LR, Frey SE, Blattner WA, Wyatt LS, Moss B, Robinson HL; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2011 Mar 1;203(5):610-9. doi: 10.1093/infdis/jiq105. Epub 2011 Jan 31.
PMID: 21282192BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Thomas Greenough, MD
University of MA Medical School (UMMS)-II Biotech
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 24, 2013
First Posted
July 26, 2013
Primary Completion
November 1, 2014
Last Updated
November 11, 2021
Record last verified: 2013-08