HIV Vaccine for HIV Prevention

Not currently recruiting at 5 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: PrEP

Must not be taking: Glucocorticoids, Immunoglobulin, others

Disqualifiers: Pregnancy, Obesity, Diabetes, Seizure, others

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine regimen, 426c.Mod.Core-C4b, to prevent HIV by activating specific immune cells that combat the virus. Researchers aim to determine if an alternative administration method can enhance the body's ability to produce protective antibodies. The trial includes several groups receiving different doses and schedules to identify the most effective approach. Individuals at low risk for HIV, including those on preventive medication (PrEP) for over six months, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new vaccine regimen.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like systemic glucocorticoids or recent vaccines might affect eligibility, so it's best to discuss your specific situation with the trial team.

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

Research has shown that the 426c.Mod.Core-C4b vaccine, combined with 3M-052-AF and Alum, is generally safe and well-tolerated. In earlier studies, participants did not experience severe side effects from this vaccine. The main goal was to enhance the immune response without causing major issues. While specific details on side effects weren't provided, the Phase 1 trial focuses on closely monitoring safety. This phase primarily ensures the vaccine's safety for humans before testing in larger groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential HIV vaccine, 426c.Mod.Core-C4b, because it aims to prevent HIV infection by stimulating the body's immune response to produce broadly neutralizing antibodies. Unlike current options, which mostly involve daily antiretroviral therapies to manage the virus, this vaccine approach could offer a long-term, preventive solution. The trial explores different dosing strategies with both bolus and fractionated delivery methods, which might enhance the body's immune response by optimizing how and when the vaccine is administered. This innovative approach could significantly change how we approach HIV prevention in the future.

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

Research shows that the 426c.Mod.Core-C4b vaccine, which participants in this trial may receive, is designed to help the immune system create antibodies that protect against various types of HIV. Studies have found that antibodies from the VRC01 class can stop HIV by preventing the virus from entering cells. Early results suggest that the 426c.Mod.Core-C4b vaccine, when combined with substances that enhance the immune response, helps produce these protective antibodies. The vaccine uses a "germline-targeting" method, aiming to develop these antibodies from their earliest stage. This method could help the body defend against HIV, even if the virus changes over time. ^{1 4 6 7 8}

Who Is on the Research Team?

Hyman Scott, MD

Principal Investigator

University of California, San Francisco

Kristen Cohen, MD

Principal Investigator

Fred Hutch Cancer Center, Seattle, WA

Are You a Good Fit for This Trial?

Healthy adults aged 18-55, at low risk for HIV, not pregnant or breastfeeding, with stable vital signs and normal blood work. Participants must understand the study details and consent to follow-up visits including lymph node sampling. They should not be on other investigational drugs or have conditions that could affect vaccine response.

Inclusion Criteria

I am willing and able to understand and sign the consent form.

Agrees not to enroll in another study of an investigational agent during participation in the trial

Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN)

Exclusion Criteria

Investigator concern for difficulty with venous access based upon clinical history and physical examination

International normalized ratio (INR) >1.2

I do not have a spleen or my spleen does not work properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming Regimen

Participants receive priming vaccine regimens to activate and induce the maturation of cross-reactive CD4 binding site antibodies

3 months

2 visits (in-person)

Boost Regimen

Optional boost regimen with BG505 SOSIP.GT1.1 gp140 to further mature B-cell lineages

3 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

64 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 426c.Mod.Core-C4b

Trial Overview The trial is testing different doses of a 'germline-targeting' HIV vaccine called 426c.Mod.Core-C4b against a placebo. It aims to see if the vaccine can induce special antibodies known as VRC01-class that are effective across all types of HIV strains.

How Is the Trial Designed?

Group I: Optional Boost Regimen with BG505 Experimental Treatment 1 Intervention

SOSIP.GT1.1 gp140

Group II: Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose Experimental Treatment 2 Interventions

The first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.

Group III: Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose Experimental Treatment 2 Interventions

The first dose for the Fractionated Delivery Arm Group 1 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.

Group IV: Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose Experimental Treatment 2 Interventions

The Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.

Group V: Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose Experimental Treatment 2 Interventions

The Bolus Delivery Arm Group 1 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.

Group VI: Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo Placebo Group 1 Intervention

The Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.

Group VII: Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo Placebo Group 1 Intervention

The first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Published Research Related to This Trial

The study tested HIV clade B/C vaccine candidates in macaques and found that high doses of Aluminum hydroxide (Alum) led to protective serum IgG responses, reducing the risk of acquiring Tier 1 SHIV-C viruses.

In contrast, low doses of Alum increased the risk of acquiring Tier 2 SHIV-C viruses, while the MF59 adjuvant showed a different immune response that effectively decreased the risk of Tier 1 SHIV-C acquisition, highlighting the importance of the adjuvant type in vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. Schifanella, L., Barnett, SW., Bissa, M., et al.[2020]

The Trimer 4571 HIV-1 vaccine was found to be safe and well-tolerated in a phase I trial involving 16 HIV-negative adults, with mild to moderate side effects and no serious adverse events reported.

The vaccine induced specific antibody responses in 44% of participants, particularly at the higher 500 mcg dose, suggesting its potential as a component in future HIV vaccine strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. Houser, KV., Gaudinski, MR., Happe, M., et al.[2022]

A phase 1 trial involving 36 healthy participants demonstrated that shorter, 6-month regimens of a mosaic HIV-1 vaccine elicited strong immune responses comparable to a longer, 12-month regimen, suggesting they could be effective for HIV prevention.

All vaccine regimens were well tolerated, with mild-to-moderate side effects reported, indicating a favorable safety profile, which is crucial for community-level vaccine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). Stephenson, KE., Wegmann, F., Tomaka, F., et al.[2021]

The RV306 trial, involving 367 healthy HIV-uninfected participants, found that additional vaccine boosts at longer intervals after the initial RV144 regimen significantly improved immune responses, particularly in antibody levels against HIV antigens.

No serious vaccine-related adverse events were reported, indicating that the additional boosts were safe and well-tolerated, which is crucial for the potential efficacy of the vaccine in preventing HIV acquisition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. Pitisuttithum, P., Nitayaphan, S., Chariyalertsak, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06796686?term=HVTN&cond=HIV&aggFilters=status:rec&viewType=Table&rank=2

Study Details | NCT06796686 | Clinical Trial to Evaluate ... This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M- ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/569396

Clinical Trial to Evaluate the Safety and Immunogenicity of a ... This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M ...

3. uab.edu uab.edu/reporter/clinical-trials/426c-mod-core-c4b-adjuvanted-with-3m-052-af-alum-immunization-in-combination-with-an-antiretroviral-analytical-treatment-interruption-ati-in-people-living-with-hiv-for-elicitation-of-vrc01-lineage-antibodies

426c.Mod.Core-C4b adjuvanted with 3M-052-AF + Alum ... A study looking at testing an experimental HIV vaccine with an experimental adjuvant to see how the immune responses change among participants.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10552837/

Discovery medicine – the HVTN's iterative approach to ... HVTN 301 (NCT05471076) uses a VRC01-class-germline targeting immunogen known as the 426c.Mod.Core-C4b, a self-assembling 7-mer nanoparticle, adjuvanted with 3M- ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06796686/clinical-trial-to-evaluate-the-safety-and-immunogenicity-of-a-priming-regimen-of-426cmodcore-c4b-followed-by-hxb2wtcore-c4b-boosts-both-adjuvanted-with-3m-052-af-alum-in-adult-participants-without-hiv-and-in-overall-good-health

Clinical Trial to Evaluate the Safety and Immunogenicity of ... This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M ...

6. ctv.veeva.com ctv.veeva.com/study/comparing-the-safety-and-immunogenicity-of-426cmodcore-c4b-vaccine-adjuvanted-with-3m-052-af-alu

Safety & Immunogenicity of 426c.Mod.Core-C4b Vaccine With ... This study will compare the safety and immunogenicity of an experimental HIV vaccine in infants with perinatal HIV exposure who are without HIV ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05471076

Study Details | NCT05471076 | Trial to Evaluate the Safety ... 1 gp140 adjuvated with 3M-052-AF + Alum is safe and well-tolerated and will further mature B-cell lineages elicited by 426c.Mod.Core-C4b priming regimens.

8. withpower.com withpower.com/trial/phase-1-human-immunodeficiency-virus-type-1-hiv-1-infection-6-2022-90459

HIV Vaccine for HIV Prevention · Info for Participants The 426c.Mod.Core-C4b vaccine is unique because it combines a specific HIV vaccine component with a novel adjuvant, 3M-052-AF, and Alum, ...