Evaluating the Safety and Immune Response to Two HIV Vaccine Regimens in Healthy, HIV-Uninfected Adults in the United States and South Africa
A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Homologous and Heterologous Prime-Boost Regimens Comprising DNA-HIV-PT123, NYVAC-HIV-PT1 and NYVAC-HIV-PT4, and AIDSVAX B/E in Healthy, HIV-Uninfected US and South African Adults
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
The purpose of this study is to evaluate the safety and immune response to two different HIV vaccine regimens in healthy, HIV-uninfected people in the United States and South Africa.
Trial Health
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 20, 2013
CompletedFirst Posted
Study publicly available on registry
August 23, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2017
CompletedOctober 15, 2021
October 1, 2021
August 20, 2013
October 13, 2021
Conditions
Outcome Measures
Primary Outcomes (11)
Frequency of severe local and systemic reactogenicity signs and symptoms
Including pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Measured within the initial 7-day period following each vaccination visit and followed until resolution
Frequency of adverse events (AEs)
Including by treatment arm, by body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Measured through participants' last study visit at Month 12
Reports of serious adverse events (SAEs) throughout the active surveillance period
Measured through the end of participants' 3-year follow-up period
Measurements of laboratory measures of safety
Including boxplots of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), and creatinine at baseline and following vaccinations, by treatment arm
Measured through participants' last study visit at Month 12
Magnitude and breadth of HIV-specific binding antibody responses as assessed by multiplex assay
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
HIV-specific CD4+ and CD8+ T-cell response rates
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Magnitude of HIV-specific CD4+ and CD8+ T-cell responses
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Humoral and cellular vaccine responses for each vaccine regimen in South African men with low BMI and with high BMI
Measured through participants' last study visit at Month 12
Humoral and cellular vaccine responses for each vaccine regimen in South African women with low BMI and with high BMI
Measured through participants' last study visit at Month 12
Humoral and cellular responses to DNA prime followed by NYVAC+AIDSVAX B/E in U.S. adults compared to South African adults
Measured through participants' last study visit at Month 12
Humoral and cellular responses to NYVAC prime followed by NYVAC+AIDSVAX B/E boost in U.S. adults compared to South African adults
Measured through participants' last study visit at Month 12
Secondary Outcomes (9)
Magnitude and breadth of HIV-specific binding antibody responses as assessed by multiplex assay
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
HIV-specific CD4+ and CD8+ T-cell response rates
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Magnitude of HIV-specific CD4+ and CD8+ T-cell responses
Measured 2 weeks after the second NYVAC+AIDSVAX B/E boost or final placebo injection
Humoral and cellular vaccine responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in South African women compared to South African men
Measured through participants' last study visit at Month 12
Humoral and cellular responses to DNA prime with NYVAC+AIDSVAX B/E boosts and NYVAC prime with NYVAC+AIDSVAX B/E boosts regimens in South African women
Measured through participants' last study visit at Month 12
- +4 more secondary outcomes
Study Arms (6)
Group 1A: Treatment
EXPERIMENTALParticipants will receive the DNA-HIV-PT123 vaccine administered as 1 mL intramuscularly (IM) and placebo (sodium chloride for injection, 0.9%) administered as 1 mL each in the left deltoid at Months 0 and 1. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the left deltoid and the AIDSVAX B/E vaccine administered as 1 mL IM in the right deltoid at Months 3 and 6.
Group 1B: Treatment
EXPERIMENTALParticipants will receive the DNA-HIV-PT123 vaccine administered as 1 mL intramuscularly (IM) and placebo (sodium chloride for injection, 0.9%) administered as 1 mL each in the left deltoid at Months 0 and 1. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the left deltoid and the AIDSVAX B/E vaccine administered as 1 mL IM in the right deltoid at Months 3 and 6.
Group 2A: Treatment
EXPERIMENTALParticipants will receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine, each administered as 1 mL IM in the left deltoid at Months 0 and 1. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the left deltoid, and the AIDSVAX B/E vaccine administered as 1 mL IM in the right deltoid at Months 3 and 6.
Group 2B: Treatment
EXPERIMENTALParticipants will receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine, each administered as 1 mL IM in the left deltoid at Months 0 and 1. They will then receive the NYVAC-HIV-PT1 vaccine and the NYVAC-HIV-PT4 vaccine; each will be administered as 1 mL IM in the left deltoid, and the AIDSVAX B/E vaccine administered as 1 mL IM in the right deltoid at Months 3 and 6.
Group 3A: Placebo
PLACEBO COMPARATORParticipants will receive two injections of placebo (sodium chloride for injection, 0.9%) each administered as 1 mL IM in the left deltoid at Months 0 and 1. They will then receive two injections of placebo (sodium chloride for injection, 0.9%) each administered as 1 mL IM in the left deltoid, and 1 injection of placebo (sodium chloride for injection, 0.9%) administered as 1 mL IM in the right deltoid at Months 3 and 6.
Group 3B: Placebo
PLACEBO COMPARATORParticipants will receive two injections of placebo (sodium chloride for injection, 0.9%) each administered as 1 mL IM in the left deltoid at Months 0 and 1. They will then receive two injections of placebo (sodium chloride for injection, 0.9%) each administered as 1 mL IM in the left deltoid, and 1 injection of placebo (sodium chloride for injection, 0.9%) administered as 1 mL IM in the right deltoid at Months 3 and 6.
Interventions
4 mg of DNA encoding clade C ZM96 Gag and gp140, CN54 Pol-Nef, administered IM
≥ 5x10\^6 PFU/ml encoding clade C ZM96 gp140 for a planned maximum dose of 1.2x10\^8 PFU/ml; administered IM
≥ 5x10\^6 PFU encoding ZM96 Gag and CN54 Pol-Nef, administered IM for a planned maximum dose of 1.1x10\^7 PFU/ml; administered IM
300 mcg of subtype B (MN) HIV gp120 glycoprotein and 300 mcg of subtype E (A244) HIV gp120 glycoprotein absorbed onto 600 mcg of aluminum hydroxide gel adjuvant, administered IM
Sodium Chloride for injection, 0.9%; administered IM
Eligibility Criteria
You may qualify if:
- Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
- Ability and willingness to provide informed consent
- Assessment of understanding: participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years following initial study injection
- Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
- Good general health as shown by medical history, physical exam, and screening laboratory tests
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
- Assessed by the clinic staff as being at "low risk" for HIV infection
- Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female and greater than or equal to 13.0 g/dL for participants who were born male
- White blood cell count equal to 3,300 to 12,000 cells/mm\^3
- Total lymphocyte count greater than or equal to 800 cells/mm\^3
- Remaining differential either within institutional normal range or with site physician approval
- Platelets equal to 125,000 to 550,000/mm\^3
- Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal (IULN); creatinine less than or equal to 1.1 times the IULN
- +11 more criteria
You may not qualify if:
- Blood products received within 120 days before first vaccination
- Investigational research agents received within 30 days before first vaccination
- Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or known hyperlipidemia
- Intent to participate in another study of an investigational research agent during the planned duration of this study
- Pregnant or breastfeeding
- HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 101 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
- Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA or (South Africa) Medicines Control Council (MCC). For participants who have received control/placebo in an experimental vaccine trial, the HVTN 101 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 101 PSRT on a case-by-case basis.
- Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
- Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
- Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
- Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment.)
- Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
- Immunoglobulin received within 60 days before first vaccination
- Autoimmune disease (Not excluded: mild, well-controlled psoriasis)
- Immunodeficiency
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)lead
- HIV Vaccine Trials Networkcollaborator
- IPPOX Foundationcollaborator
- EuroVacc Foundationcollaborator
- Global Solutions for Infectious Diseases (GSID)collaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Magdalena Sobieszczyk
Columbia University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 20, 2013
First Posted
August 23, 2013
Primary Completion
January 1, 2017
Last Updated
October 15, 2021
Record last verified: 2021-10