Evaluating the Safety and Immune Response to Three Different Prime-Boost HIV Vaccine Regimens in Healthy, HIV-Uninfected Adults
A Phase 1 Randomized, Double-blind, Placebo Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV-1 Vaccine Regimen of DNA Prime and NYVAC Boost With 3 Different HIV-1 Envelope Inserts (Nat-B Env, CON-S Env, and Mosaic Env) in Healthy, HIV-1-uninfected Adults
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
The purpose of this study is to test the safety and immune response to three different sets of HIV vaccines in healthy, HIV-uninfected adults.
Trial Health
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2013
CompletedFirst Posted
Study publicly available on registry
October 28, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2018
CompletedOctober 15, 2021
October 1, 2021
October 22, 2013
October 13, 2021
Conditions
Outcome Measures
Primary Outcomes (7)
Frequency and severity of local injection site reactogenicity signs and symptoms
Local injection site signs and symptoms may include pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness.
Measured for 3 days following each vaccination visit (Days 0, 28, 84, and 168)
Frequency of adverse events (AEs) categorized by the MedDRA body system, MedDRA preferred term, severity and assessed relationship to study products; detailed description of all AEs meeting DAIDS criteria for expedited reporting (EAE)
MedDRA is the Medical Dictionary for Regulatory Activities.
Measured through Day 364 visit
Laboratory measures of safety
Laboratory measures of safety include white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), alkaline phosphatase (ALK Phos), aspartate aminotransferase (AST), and creatinine.
Measured through Day 357 visit
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Measured through Day 364 visit
Breadth of the T-cell response determined as the number of reactive CD4 and CD8 T-cell epitopes using global potential T-cell epitope (PTEg) peptides
Measured through Day 182 visit
Total magnitude of CD4 and CD8 T-cell responses measured by intracellular cytokine staining (ICS) to PTEg peptide pools
Measured through Day 182 visit
Frequency and severity of systemic reactogenicity signs and symptoms
Systemic reactogenicity signs and symptoms may include fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms.
Measured for 3 days following each vaccination visit (Days 0, 28, 84, and 168)
Secondary Outcomes (6)
Breadth of the T-cell response determined as the number of reactive CD4 and CD8 T-cell epitopes to PTEg and Center for HIV/AIDS Vaccine Immunology (CHAVI) peptide set
Measured through Day 182 visit
Total magnitude of CD4 and CD8 T-cell responses measured by ICS to PTEg
Measured through Day 182 visit
Depth of the T-cell responses, determined as the variant recognition per epitope targeted by responding T cells using PTEg and CHAVI peptides
Measured through Day 182 visit
Response rate of CD4 and CD8 T-cell responses to PTEg and CHAVI peptide sets measured by ICS
Measured through Day 182 visit
Magnitude and breadth of serum neutralizing antibodies (nAbs) to a panel of standardized HIV-1 isolates
Measured through Day 364 visit
- +1 more secondary outcomes
Study Arms (6)
Group 1: study vaccines with Nat-B env insert
EXPERIMENTALParticipants in this arm will receive DNA Nat-B env vaccine injections on Day 0 and Day 28 followed by NYVAC Nat-B env vaccine injections on Day 84 and Day 164.
Group 1: placebo vaccines with Nat-B env insert
PLACEBO COMPARATORParticipants in this arm will receive placebo injections of DNA Nat-B env vaccine on Day 0 and Day 28 followed by placebo injections for NYVAC Nat-B env vaccine on Day 84 and Day 164.
Group 2: study vaccines with CON-S env insert
EXPERIMENTALParticipants in this arm will receive DNA CON-S env vaccine injections on Day 0 and Day 28 followed by NYVAC CON-S env vaccine injections on Day 84 and Day 164.
Group 2: placebo vaccines with CON-S env insert
PLACEBO COMPARATORParticipants in this arm will receive placebo injections of DNA CON-S env vaccine on Day 0 and Day 28 followed by placebo injections for NYVAC CON-S env vaccine on Day 84 and Day 164.
Group 3: study vaccines with Mosaic env insert
EXPERIMENTALParticipants in this arm will receive DNA Mosaic env vaccine injections on Day 0 and Day 28 followed by NYVAC Mosaic env vaccine injections on Day 84 and Day 164.
Group 3: placebo vaccines with Mosaic env insert
PLACEBO COMPARATORParticipants in this arm will receive placebo injections of DNA Mosaic env vaccine on Day 0 and Day 28 followed by placebo injections for NYVAC Mosaic env vaccine on Day 84 and Day 164.
Interventions
The DNA Nat-B env vaccine will be administered as a 4-mg dose injection intramuscularly (IM) by Biojector 2000 ® in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
NVYAC Nat-B env vaccine will be administered as a 3 × 10\^7 plaque forming units (pfu) dose IM by needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
The DNA CON-S env vaccine will be administered as a 4-mg dose injection IM by Biojector 2000 ® in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
NVYAC CON-S env vaccine will be administered as a 3 × 10\^7 pfu dose IM by needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
The DNA Mosaic env vaccine will be administered as a 4-mg dose injection IM by Biojector 2000 ® in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
NVYAC Mosaic env vaccine will be administered as a 3 × 10\^7 pfu dose IM by needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated).
Placebo for both DNA and NYVAC vaccines will be administered in the deltoid muscle of the non-dominant arm (unless medically contraindicated) as sodium chloride for injection, 0.9%.
All three DNA env vaccines will be administered IM in the deltoid muscle of the non-dominant arm (unless medically contraindicated) using the Biojector 2000® device.
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 for U.S. participants (5 years for participants in Switzerland) following initial study injection
- Agrees not to enroll in another study of an investigational research agent
- 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 12.5 g/dL for participants who were born female, or greater than or equal to 13.5 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: ALT, AST, and alkaline phosphatase less than 1.25 times the institutional upper limit of normal (ULN); creatinine less than or equal to ULN
- +8 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; less than or equal to 18; or 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, current smoker, 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 099 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis and the identity of the study control/placebo must be obtained.
- 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. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 099 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 099 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
- Immunodeficiency
- +18 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
- Center for HIV/AIDS Vaccine Immunology (CHAVI)collaborator
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Lindsey Baden
Brigham and Women's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2013
First Posted
October 28, 2013
Primary Completion
August 1, 2018
Last Updated
October 15, 2021
Record last verified: 2021-10