HIV Vaccines for Human Immunodeficiency Virus Infection

(DC-HIV04 Trial)

No longer recruiting at 1 trial location

Overseen By Jamie Fullerton, MPPM

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sharon Riddler

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Chemotherapy

Disqualifiers: Pregnancy, Chronic inflammatory conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 23

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new vaccine for people living with HIV. The goal is to determine if a vaccine made from a person's own white blood cells is safe and how effectively it encourages the body to fight the virus. Participants will receive one of several vaccine types, such as a1DC or pgDC combined with conserved HIV peptides or inactivated whole autologous HIV, to identify the most effective method. Individuals who have been on the same HIV treatment for at least two years, with stable low virus levels and no significant treatment interruptions, may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. However, you must have been on a stable HIV treatment (ART) for at least 24 months without changes in the last 8 weeks. If you are taking systemic immunomodulators or certain other treatments, you may need to stop those before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vaccines using dendritic cells, a type of immune cell, may help treat HIV. Various studies have tested these vaccines, finding them generally safe and well-tolerated. For example, a vaccine using dendritic cells with inactivated HIV proved safe in past studies, with participants mostly experiencing mild side effects like flu-like symptoms or minor reactions at the injection site.

Another method involves dendritic cells with small pieces of the HIV virus, called peptides. Studies on these peptide-based vaccines have also found them mostly safe. Some participants reported mild side effects, but no strong evidence of serious reactions emerged.

The current trial is testing different ways to make these vaccines. Since it is in the early stages, researchers are primarily assessing safety. Although there is limited data, the trial's progression suggests that earlier tests did not reveal major safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for HIV focus on managing the virus with antiretroviral therapy (ART), which suppresses viral replication. However, the investigational vaccines in this trial work differently by aiming to boost the immune system's ability to fight HIV directly. Researchers are excited about these treatments because they use dendritic cells (DCs) loaded with specific components of the HIV virus, including conserved peptides and inactivated autologous HIV, to stimulate a stronger and more targeted immune response. This approach could potentially offer a more durable solution by training the body's own defenses to recognize and combat HIV more effectively than current options.

What evidence suggests that this trial's vaccines could be effective for HIV?

Research has shown that dendritic cell vaccines, studied in this trial, may help reduce the amount of HIV in the body. Participants will receive different versions of these vaccines, including those combined with inactivated whole autologous HIV or conserved HIV peptides. Studies have found that these vaccines can reduce the virus by up to 94% after treatment. They work by using a person's own immune cells to identify and fight the virus. Additionally, research on peptide-based vaccines, also included in this trial, suggests they can create strong immune responses. Early results are promising, but more research is needed to understand the long-term effects. ^{1 2 6 7 8}

Who Is on the Research Team?

Bernard Macatangay, MD

Principal Investigator

University of Pittsburgh

John Mellors, MD

Principal Investigator

University of Pittsburgh

Sharon Riddler, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

Adults aged 18-70 with stable HIV infection, on continuous ART for at least 24 months, and undetectable viral load for over two years. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception if necessary, and have no history of certain chronic conditions or recent hospitalizations.

Inclusion Criteria

Creatinine ≤ 1.5x upper limit of normal (ULN)

Platelet count ≥100,000/mm3

All participants must agree not to participate in the conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormone-based contraceptive), while receiving study treatment and for 12 weeks following the final study vaccine.

Exclusion Criteria

I am on a low dose of steroids or use inhaled/topical steroids and will continue them during the study.

I started HIV treatment early after diagnosis.

Lack of adequate venous access that, in the opinion of the investigator, would interfere with study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Step 1

Participants undergo initial tests, procedures, and exams. Randomization into study groups occurs at Week 4.

12 weeks

4 visits (in-person)

Step 2

Participants receive 6 study vaccinations at 4-week intervals and are monitored for health, safety, and immune response.

68 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• a1DC + conserved HIV peptides
• a1DC + inactivated whole autologous HIV
• a1DC + no antigen
• pgDC + conserved HIV peptides
• pgDC + inactivated whole autologous HIV
• pgDC + no antigen

Trial Overview The trial is testing a personalized vaccine made from participants' white blood cells against HIV. It aims to see which of the four vaccine-making methods works best in terms of safety and immune response enhancement.

How Is the Trial Designed?

Group I: ARM E Experimental Treatment 1 Intervention

pgDC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose

Group II: ARM D Experimental Treatment 1 Intervention

pgDC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose

Group III: ARM B Experimental Treatment 1 Intervention

a1DC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose

Group IV: ARM A Experimental Treatment 1 Intervention

a1DC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose

Group V: ARM C Active Control 1 Intervention

a1DC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose

Group VI: ARM F Active Control 1 Intervention

pgDC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose

Who Is Running the Clinical Trial?

Sharon Riddler

Lead Sponsor

Trials

3

Recruited

90+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03758625

Study Details | NCT03758625 | Comparison of Dendritic ... This study will be done in people living with HIV to see if an investigational vaccine made from a person's own white blood cells is safe and tolerated.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6789779/

Peptide-Based Vaccination for Antibody Responses Against HIV Here, we will review the major peptide-carrier based approaches in the vaccine field and their application and recent development in the HIV-1 field.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3046258/

Preclinical evaluation of HIV-1 therapeutic ex vivo dendritic ... We found that cytokine-matured DC loaded with Gag RNA were able to induce Gag-specific IFN-γ and IL-2 responses after a 12-day coculture.

4. sciencedirect.com sciencedirect.com/science/article/pii/S141386702300034X

Conserved multiepitope vaccine constructs: A potent HIV-1 ... This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical ...

5. journals.asm.org journals.asm.org/doi/10.1128/CVI.00221-07

Therapeutic Immunization with Human Immunodeficiency ... Our trial examined the safety and efficacy of a therapeutic vaccine in HIV-1-infected subjects on ART. ... HIV-1 peptides was achieved following peptide-pulsed DC ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2692338/

Safety and Immunogenicity of a CTL Multiepitope Peptide ... The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309913703438

Safety and efficacy of the peptide-based therapeutic ... Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4×, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag, in ...

8. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(13)70343-8/abstract

a phase 2 randomised, double-blind, placebo-controlled trial Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4×, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains ...