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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment VRC07 delivered via AAV8 for HIV infection?

The study showed that the AAV8-VRC07 treatment was safe and well-tolerated, with participants producing measurable amounts of the VRC07 antibody, which remained stable for up to 3 years. This suggests that the treatment can durably produce active antibodies in the body, potentially adding a new tool in fighting HIV. ^{1 2 3 4 5}

Is the AAV8-delivered antibody treatment for HIV safe for humans?

In a study with eight adults living with HIV, the AAV8-delivered antibody treatment was found to be safe and well tolerated, with no significant changes in important health markers over 1-3 years of follow-up. ^{4 6 7 8 9}

How is the AAV8-delivered VRC07 treatment for HIV different from other treatments?

The AAV8-delivered VRC07 treatment is unique because it uses a viral vector to deliver DNA that enables the body to produce its own broadly neutralizing antibodies against HIV, potentially reducing the need for repeated antibody infusions. This approach offers a novel way to maintain long-term antibody levels with a single intramuscular injection, unlike traditional treatments that require ongoing medication or infusions. ^{1 4 5 8 10}

What is the purpose of this trial?

Background: The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a gene that could be transferred to the cells of people with HIV. The gene should tell the cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged into a man-made version of a virus called AAV8. Objectives: 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 health and have been taking the same HIV medicine for at least 3 months Design: Participants were screened in a different protocol. Participants received the study product on day 1. It was injected one or more times in the upper arm or thigh using a needle. Participants weight was measured to calculate the dose. Women may have had a pregnancy test. For 7 days after getting the study product, participants checked their temperature with a thermometer. They noted any symptoms in an electronic or paper diary. Participants will have study visits. At each one, they will have a physical exam and medical history. They will have blood drawn and may have saliva collected. The study visit schedule is as follows: For 12 weeks: 1 visit a week For the next 12 weeks: 1 visit every other week Then about 1 visit a month After 1 year in the study: a visit every 6 months for the next 4 years. Total study participation is 5 years.

Research Team

Joseph P Casazza, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

I am in good health with no significant medical issues.

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 have been on a consistent HIV medication regimen for at least 3 months.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Vectored delivery of anti-SIV envelope targeting mAb via AAV8 protects rhesus macaques from repeated limiting dose intrarectal swarm SIVsmE660 challenge. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Expression of HIV-1 broadly neutralizing antibodies mediated by recombinant adeno-associated virus 8 in vitro and in vivo. [2018]