AAV8-Delivered Antibody for HIV Infection

(VRC 603 Trial)

Overseen By Laura Novik, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Antiretrovirals

Must not be taking: Monoclonal antibodies

Disqualifiers: Opportunistic infections, Drug use, Hypertension, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help the body fight HIV by using a specially crafted gene that instructs cells to produce an antibody known as VRC07. The trial aims to determine if this method, delivered through a harmless virus called AAV8, is safe and effective in producing the antibody. It targets people living with HIV who are otherwise healthy and have maintained the same HIV treatment for at least three months. Participants will receive an injection and attend regular follow-up visits over five years to monitor their health and the treatment's effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the unique 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 HIV medications. In fact, you must have been on a stable HIV treatment for at least 3 months to participate.

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

Research has shown that the AAV8-VRC07 treatment is generally safe for humans. Studies have found that injecting AAV8-VRC07 into muscles is well tolerated. Participants did not experience significant changes in key health indicators, such as CD4 T cell count (a type of immune cell) or viral load (the amount of virus in the body).

In earlier studies, participants did not have allergic reactions or develop anti-drug antibodies, which occur when the body mistakenly attacks the treatment. This suggests that the treatment does not cause unwanted immune responses.

Overall, findings so far indicate that AAV8-VRC07 is a promising and safe option for people living with HIV. However, as with any new treatment, ongoing studies are important to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the AAV8-delivered VRC07 treatment for HIV because it offers a novel approach by using gene therapy to deliver antibodies directly into the body. Unlike standard treatments such as antiretroviral therapy (ART) that require daily medication adherence, AAV8-VRC07 aims to provide long-lasting protection with a single intramuscular injection. This method utilizes the AAV8 vector to introduce the VRC07 antibody gene, enabling the body to produce its own HIV-targeting antibodies, potentially reducing the virus's ability to replicate. This innovative approach could transform HIV management by simplifying treatment while offering sustained viral suppression.

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

Research has shown that the AAV8-VRC07 treatment could be promising for treating HIV. VRC07 is an antibody that fights HIV, and AAV8 is a virus used to deliver the gene that produces this antibody into human cells. Participants in this trial will receive different dosages of AAV8-VRC07. Early findings suggest that after receiving the treatment, the amount of HIV in the blood decreased significantly over three weeks, indicating that the treatment might effectively reduce the virus in the body. Previous studies found that AAV8-VRC07 was safe and well-tolerated, with no major changes in important immune markers like CD4 T cell count. These early results are encouraging for those considering joining the trial. ^{1 2 3 6 7}

Who Is on the Research Team?

Joseph P Casazza, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults aged 18-65 living with HIV, in good health, on stable HIV medication for at least 3 months. Participants must agree to use contraception and not be pregnant or breastfeeding. Excludes those with previous monoclonal antibody treatment, certain pre-existing antibodies, heavy weight (for Group 3), uncontrolled hypertension, active liver disease or severe allergies.

Inclusion Criteria

Willing to maintain or establish a relationship with a primary health care provider for medical management of HIV infection while participating in the study

I am in good health with no significant medical issues.

Available for clinical follow-up through the last study visit

Exclusion Criteria

I have an ongoing liver condition like chronic hepatitis.

My high blood pressure is not controlled by medication.

I weigh more than 115 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants receive AAV8-VRC07 via intramuscular injection, with dose escalation based on safety and VRC07 concentration in blood

12 weeks

1 visit per week

Extended Monitoring

Participants have study visits every other week for 12 weeks, then monthly visits to monitor safety and VRC07 antibody levels

12 weeks

1 visit every other week, then monthly

Long-term Follow-up

Participants are monitored for safety and effectiveness, with visits every 6 months for 4 years

4 years

1 visit every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• VRC07

Trial Overview The trial tests AAV8-VRC07's safety and its ability to make cells produce the VRC07 antibody against HIV. It involves a gene packaged into a man-made virus injected into participants' arms or thighs. The study spans over five years with regular visits for physical exams and sample collections.

How Is the Trial Designed?

Group I: Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) Experimental Treatment 1 Intervention

AAV8-VRC07 (2.5 x 10\^12 vg/kg) administered by IM injection (Day 0)

Group II: Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) Experimental Treatment 1 Intervention

AAV8-VRC07 (5 x 10\^11 vg/kg) administered by IM injection (Day 0)

Group III: Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) Experimental Treatment 1 Intervention

AAV8-VRC07 (5 x 10\^10 vg/kg) administered by intramuscular (IM) injection (Day 0)

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

VRC01, a monoclonal antibody, effectively distributes to mucosal sites in both male and female participants, showing quantifiable levels in rectal and vaginal tissues after intravenous infusion.

The antibody demonstrated protective function by significantly reducing HIV-1 infection in rectal explants from VRC01 recipients compared to controls, particularly against a sensitive strain of the virus, indicating its potential as a preventive treatment against HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. Astronomo, RD., Lemos, MP., Narpala, SR., et al.[2022]

The monoclonal antibody VRC01, designed to neutralize diverse HIV-1 strains, was found to be safe and well-tolerated in a Phase I study involving 28 healthy adults, with no serious adverse events reported.

VRC01 demonstrated expected pharmacokinetics, including a terminal half-life of 15 days and effective serum concentrations, which supports its potential use in future HIV-1 prevention studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Ledgerwood, JE., Coates, EE., Yamshchikov, G., et al.[2022]

In a study involving 107 HIV-1 infected and 82 non-infected recipients of the VRC01 antibody, higher serum concentrations of VRC01 were associated with a lower risk of HIV-1 acquisition, indicating that VRC01 concentration is a potential marker for effective dosing.

The research suggests that fixed dosing of VRC01 may be as effective as body weight-based dosing for preventing HIV-1, which could simplify future treatment regimens in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition. Seaton, KE., Huang, Y., Karuna, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9876739/

Safety and tolerability of AAV8 delivery of a broadly ... In this cohort, IM injection of AAV8-VRC07 was safe and well tolerated. No clinically significant change in CD4 T cell count or VL occurred during the 1–3 years ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35411076/

Safety and tolerability of AAV8 delivery of a broadly ... - PubMed In this cohort, IM injection of AAV8-VRC07 was safe and well tolerated. No clinically significant change in CD4 T cell count or VL occurred ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03374202

NCT03374202 | Safety and Tolerability of AAV8 Delivery of ... To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody. Eligibility: Adults ages 18-65 who are HIV infected but in general good ...

4. biorxiv.org biorxiv.org/content/10.1101/2024.07.11.603156v3.full.pdf

HIV broadly neutralizing antibody escape dynamics drive ... In contrast, following AAV8-VRC07 treatment, viral loads decreased precipitously over a three-week period, which diverged . CC-BY-NC-ND 4.0 ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/vrc07-523ls/patient

VRC07-523LS Patient Drug Record | NIH Selected Study Results: Results presented at CROI 2025 showed that vesatolimod and the bNAbs VRC07-523LS and CAP256V2LS were safe, with no treatment-related ...

6. nature.com nature.com/articles/s41591-024-03247-5

Safety and antiviral effect of a triple combination of HIV-1 ... These data show that the triple-bNAb cocktail maintained virologic suppression for >28 weeks in the majority of PLWH in this trial, with viral ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03374202?term=vrc07&viewType=Table&checkSpell=&rank=1

Study Details | Safety and Tolerability of AAV8 Delivery of a ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...