Safety and Immune Response to a Clade C DNA HIV Vaccine
HVTN111
A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA and of MF59-adjuvanted Clade C Env Protein, in Healthy, HIV-uninfected Adult Participants
1 other identifier
interventional
132
2 countries
2
Brief Summary
The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 hiv-infections
Started Jun 2016
Typical duration for phase_1 hiv-infections
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 21, 2016
CompletedFirst Submitted
Initial submission to the registry
December 16, 2016
CompletedFirst Posted
Study publicly available on registry
December 20, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 11, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 11, 2018
CompletedJune 21, 2019
June 1, 2019
2.1 years
December 16, 2016
June 19, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (10)
Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)
Measured through Month 12
Frequency of adverse events (AEs)
By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Measured through Month 12
Frequency of serious adverse events (SAEs), adverse events of special interest (AESIs), and new chronic conditions (requiring medical intervention for 30 days or more)
Measured through Month 12
Composite of safety laboratory measures: white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), and creatinine
Measured through Month 12
Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration
Measured through Month 12
HIV-specific total immunoglobulin G (IgG) binding antibody response breadth and magnitude as assessed by multiplex assay
Measured through Month 6.5
Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay
Measured through Month 6.5
Presence of neutralizing antibody responses against HIV-1 isolates
Measured through Month 6.5
HIV-specific CD4+ T-cell responses as assessed by flow cytometry
Measured through Month 6.5
HIV-specific CD8+ T-cell responses as assessed by flow cytometry
Measured through Month 6.5
Study Arms (6)
Group 1: DNA + Placebo + Protein/MF59
ACTIVE COMPARATORParticipants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6. All injections are via needle and syringe.
Group 2: DNA + Placebo + Protein/MF59
ACTIVE COMPARATORParticipants will receive the DNA-HIV-PT123 vaccine in the left deltoid at months 0, 1, and 6. They will receive placebo in both deltoids at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6. All injections are via needle and syringe.
Group 3: Placebo
PLACEBO COMPARATORParticipants will receive placebo in both deltoids at months 0, 1, 3, and 6. All injections are via needle and syringe.
Group 4: DNA + Placebo + Protein/MF59
ACTIVE COMPARATORParticipants will receive the DNA-HIV-PT123 vaccine via Biojector in the left deltoid at months 0, 1, 3, and 6. They will receive placebo in the right deltoid at months 0 and 1, and the Protein/MF59 vaccine at months 3 and 6, via needle and syringe.
Group 5: DNA + Placebo + Protein/MF59
ACTIVE COMPARATORParticipants will receive the DNA-HIV-PT123 vaccine at months 0, 1, and 6, and placebo at month 3, in the left deltoid via Biojector. They will receive placebo at month 3, and the Protein/MF59 vaccine at months 0, 1, and 6, in the right deltoid via needle and syringe.
Group 6: Placebo
PLACEBO COMPARATORParticipants will receive placebo in the left deltoid via Biojector, and in the right deltoid via needle and syringe, at months 0, 1, 3, and 6.
Interventions
Contains a mixture of 3 DNA plasmids in a 1:1:1 ratio, each at 1.33 mg: 1) clade C ZM96 gag, 2) clade C ZM96 gp140, and 3) clade C CN54 pol-nef, delivered at a total dose 4 mg administered as 1 mL intramuscularly (IM)
clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered as 0.5 mL IM
Sodium Chloride, 0.9%, administered by IM injection at volumes to match the active products
Eligibility Criteria
You may qualify if:
- General and Demographic Criteria
- Age of 18 to 40 years
- Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study
- Ability and willingness to provide informed consent
- Assessment of understanding: volunteer demonstrates understanding of this study; provides answers to a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
- 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
- HIV-Related Criteria:
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
- Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.
- Hemogram/Complete blood count (CBC)
- Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
- White blood cell count = 3,300 to 12,000 cells/mm\^3
- Total lymphocyte count ≥ 800 cells/mm\^3
- +25 more criteria
You may not qualify if:
- General
- Blood products received within 120 days before first vaccination
- Investigational research agents received within 30 days before first vaccination
- Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia
- Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 111 study
- Pregnant or breastfeeding Vaccines and other Injections
- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 111 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. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 111 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 111 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 (eg, 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 (eg, 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 Immune System
- Immunosuppressive medications received within 168 days before first vaccination. (Not excluded from participation: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses \< 2 mg/kg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment.
- Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
- Immunoglobulin received within 60 days before first vaccination
- Autoimmune disease
- +27 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
- Novartis Vaccinescollaborator
Study Sites (5)
Aurum Tembisa CRS
Johannesburg, Gauteng, 1632, South Africa
Isipingo CRS
Westville, KwaZulu-Natal, 3630, South Africa
Aurum Institute Klerksdorp CRS
Klerksdorp, North West, 2571, South Africa
National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
Mbeya, Tanzania
Matero Reference Clinic CRS
Lusaka, Zambia
Related Publications (3)
Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.
PMID: 40190112DERIVEDHanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.
PMID: 34895272DERIVEDHosseinipour MC, Innes C, Naidoo S, Mann P, Hutter J, Ramjee G, Sebe M, Maganga L, Herce ME, deCamp AC, Marshall K, Dintwe O, Andersen-Nissen E, Tomaras GD, Mkhize N, Morris L, Jensen R, Miner MD, Pantaleo G, Ding S, Van Der Meeren O, Barnett SW, McElrath MJ, Corey L, Kublin JG; HVTN 111 Protocol Team. Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein. Clin Infect Dis. 2021 Jan 23;72(1):50-60. doi: 10.1093/cid/ciz1239.
PMID: 31900486DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Mina Hosseinipour
UNC Project- Lilongwe
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
December 16, 2016
First Posted
December 20, 2016
Study Start
June 21, 2016
Primary Completion
July 11, 2018
Study Completion
July 11, 2018
Last Updated
June 21, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will not share