Clinical trial NCT06919016: A Study to Evaluate the Safety and Immunogenicity of the V3-region Directed Immunogens DV700P-RNA Followed by DV701B1.1-RNA in Adults Without HIV
Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of the V3-region Directed Immunogens DV700P-RNA (Prime) Followed by DV701B1.1-RNA (Boost) in Adult Participants Without HIV
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: HIV-1-infection
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institutes of Health (NIH)
name: Department of Health and Human Services
First posted: 2025-04-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This is a phase 1, first-in-human (FIH) trial for two vaccines, DV700P-RNA and DV701B1.1-RNA. This means it is the first time these study products are being tested in people.

The purpose of this study is to see if the study products are safe, if people are able to take them without becoming too uncomfortable, and how a person's immune system responds to them (a person's immune system protects them from infections and disease).

Forty-five volunteers without HIV and in overall good health, aged 18 to 55 years, will be enrolled and be in this study for about 16 months (about 12 visits), Study procedures will include blood draws, injections, and the collection of white blood cells and cells from their lymph nodes.


Eligibility criteria: Inclusion Criteria:

* Understands the study and agrees to complete the consent process.
* Can attend all clinic visits until the end of the study.
* Agrees to follow all study procedures.
* Will not join another study with experimental treatments during this trial, unless approved by both study sponsors.
* Generally healthy according to the study doctor.
* Physical exam and lab results show no major issues that could affect safety or study results.
* Agrees to discuss HIV risk and prevention.
* Hemoglobin levels: at least 11.0 g/dL for women and 13.0 g/dL for men.
* White blood cell count between 2,500 to 12,000/mm³ (higher levels okay if health is otherwise good and approved).
* Platelet count between 125,000 to 550,000/mm³.
* ALT enzyme level less than 2.5 times the upper limit of normal.
* Serum creatinine level within 1.1 times the upper limit of normal.
* Serum calcium level at least 8.5 mg/dL.
* Blood pressure within acceptable range (systolic 90-140 mmHg, diastolic 50-90 mmHg), with average below 140/90 mmHg and no single reading over 160/100 mmHg.
* Negative HIV test.
* Negative for Hepatitis C.
* Negative for Hepatitis B.
* Women who can become pregnant must use effective contraception from 21 days before joining the study until 8 weeks after the last vaccination and must have a negative pregnancy test on enrollment day.
* Women of pregnancy potential must agree not to seek pregnancy through methods like IVF from 21 days before joining the study until 8 weeks after the last vaccination.

Exclusion Criteria:

* Breastfeeding or pregnant.
* Body mass index (BMI) of 40 or higher, unless in good health and approved.
* Diabetes, unless it is well-controlled Type 2 diabetes or gestational diabetes.
* Previous or current investigational HIV vaccine recipients (placebo recipients are allowed).
* Received non-HIV investigational vaccines within the last year, unless they are now licensed or authorized.
* Immunodeficiency or medications that impair immune response, such as high-dose steroids.
* Received blood products or immunoglobulin within 16 weeks before enrollment.
* Received certain vaccines within the last 4 weeks before enrollment.
* Received other vaccines within 14 days before enrollment.
* History of myocarditis or pericarditis.
* Started allergy immunotherapy in the past year (unless stable and approved).
* Taken investigational research agents recently.
* Serious allergic reactions to any mRNA vaccine or drugs containing polyethylene glycol.
* History of hereditary or acquired angioedema.
* Any episode of hives (urticaria) within the past year.
* Chronic hives (urticaria).
* Hives previously caused by immunization.
* Bleeding disorder that would make study procedures unsafe.
* Seizures or use of seizure medications in the past 3 years.
* Absence of spleen or non-functional spleen.
* Active duty and reserve US military personnel.
* Any other significant condition that could affect safety or participation, including substance use, psychiatric disorders, recent suicide attempts, or cancer with potential for recurrence.
* Asthma that requires frequent or high-dose medication, recent emergency care, or multiple daily medications.
* History of certain immune-mediated conditions (mild, localized conditions may be okay).
* Allergy to local anesthetics like Novocaine or Lidocaine.
* Difficulty with venous access, such as history of intravenous drug use or problems with blood draws.

Primary outcomes:
measure: Incidence of local reactogenicity signs and symptoms
timeFrame: At days 15, 71, 183 and 295 (14 days following receipt of any study vaccine)
measure: Incidence of systemic reactogenicity signs and symptoms
timeFrame: At days 15, 71, 183 and 295 (14 days following receipt of any study vaccine)
measure: Number of participants experiencing Serious adverse events (SAEs)
timeFrame: Baseline through Month 22
measure: Number of participants experiencing medically attended adverse events (MAAEs)
timeFrame: Baseline through Month 22
measure: Number of participants experiencing adverse events of special interest (AESIs)
timeFrame: Baseline through Month 22
measure: Number of participants experiencing adverse events (AEs) leading to early participant withdrawal or permanent discontinuation will be collected throughout the study
timeFrame: Baseline through Month 22
measure: Response rate of V3G-specific IgG+ B cells, as assessed by flow cytometry
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Response rate of differential serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by the TZM-bl assay
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Magnitude of differential serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by the TZM-bl assay
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
Secondary outcomes:
measure: Response rate of serum IgG binding antibodies to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Magnitude of serum IgG binding antibodies to autologous and heterologous HIV Env stabilized trimers, as assessed by BAMA
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Response rate of serum antibody (Ab) neutralization of heterologous tier 2 HIV-1 strains, as measured by TZM-bl assay
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Magnitude of serum Ab neutralization of heterologous tier 2 HIV-1 strains, as measured by TZM-bl assay
timeFrame: At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)
measure: Frequency of V3G bnAb lineage sequences, as measured by B-cell receptor (BCR) single-cell sequencing of V3G-specific IgG+ B cells
timeFrame: Baseline though Month 22
measure: Epitope-specific response rates, as measured by electron microscopy-based polyclonal epitope mapping (EMPEM)
timeFrame: At week 42 (2 weeks after the fourth vaccinations)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Medical Center (Site ID: 31788)
state: Alabama
city: Decatur
country: United States
facility: Hope Clinic (Site ID: 31440)
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital (Site ID: 31788)
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center (Site ID: 10032)
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center (Site ID: 31467)
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh (Site ID: 1001)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site ID: 30352)
state: Tennessee
city: Seattle
country: United States
facility: Seattle (Site ID: 30331)
state: Washington
Study officials:
References: