Antibody Treatment for HIV

Overseen By VRC Clinic

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Cytotoxics, others

Disqualifiers: Pregnancy, Hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 15

Duration: 6-11 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive or cytotoxic medications, you must not have taken them for more than 10 days in the 4 weeks before enrolling, and not at all in the 14 days before enrolling.

What data supports the effectiveness of the drug VRC-HIVMAB0121-00-AB, CAP256J3LS for treating HIV?

Research on a similar drug, VRC01, shows it can prevent HIV-1 infection in sensitive strains by neutralizing the virus, as seen in trials where it reduced infection rates in tissue samples and decreased virus levels in some untreated patients. This suggests that similar treatments might also be effective in preventing or managing HIV. ^{1 2 3 4 5}

Is the antibody treatment for HIV, known as VRC-HIVMAB0121-00-AB or CAP256J3LS, safe for humans?

The antibody treatment, similar to VRC01 and VRC07-523LS, has been shown to be safe and well tolerated in humans during clinical trials, with no serious side effects reported. ^{2 3 6 7 8}

How is the drug CAP256J3LS different from other HIV treatments?

CAP256J3LS is a monoclonal antibody treatment that targets the HIV virus in a unique way by binding to specific sites on the virus, potentially offering a new approach compared to traditional antiretroviral drugs that often target viral replication. This type of treatment may help overcome issues like drug resistance and side effects associated with existing HIV medications. ^{2 3 6 8 9}

What is the purpose of this trial?

Background: HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immunodeficiency syndrome). Researchers want to find new ways to treat or prevent HIV infection. CAP256J3LS is a new product that uses antibodies. Antibodies are naturally occurring proteins; they target and disable disease-causing agents such as viruses. This new product may be able to stop HIV infections. Objective: To test the safety of CAP256J3LS in healthy people. Eligibility: People aged 18 to 60 years in good general health. Design: CAP256J3LS can be administered in 2 ways: (1) by a shot under the skin into the belly fat or (2) through a tube inserted into a vein in the arm. Participants will be divided into 6 groups: The study will open with the lowest dose of study product. The dose groups are spaced out to allow the study team to look over the safety data in each group. If there are no safety concerns in the lowest dose, then the next higher dose groups will be enrolled. This pattern will continue until all dose groups are enrolled. Also, some participants will receive only 1 dose; others will receive 3 doses, each spaced 12 weeks apart. Those who receive only 1 dose of the study drug will have 14 clinic visits over 6 months. Those who get 3 doses will have 27 visits over 11 months. Participants will provide blood samples at each visit. Urine samples may also be needed. All participants will get a thermometer and a measuring tool. They will measure any redness, swelling, or bruising they have at the injection site. They will check their temperature every day for 7 days after receiving the study drug. They will record their highest temperatures and any symptoms they have....

Research Team

Joseph P Casazza, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

This trial is for healthy adults aged 18 to 60 who may help in finding new treatments or prevention methods for HIV/AIDS. Participants will be testing the safety of a new antibody product, CAP256J3LS.

Inclusion Criteria

I had a physical exam in the last 56 days with no major health issues found.

Participant must be willing and able to complete the informed consent process

Participant must be able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process

Exclusion Criteria

My weight is over 115 kg.

My high blood pressure is not well controlled.

I am currently breastfeeding or planning to get pregnant during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive CAP256J3LS either as a single dose or in repeat doses, with doses spaced 12 weeks apart

6-11 months

14-27 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including reactogenicity and adverse events

24 weeks after last product administration

Treatment Details

Interventions

• VRC-HIVMAB0121-00-AB

Trial Overview The study tests CAP256J3LS, an antibody that might prevent HIV infection. It's given either as a shot under the skin or through a vein. Participants are grouped to receive one dose or three doses over several months with regular clinic visits and health monitoring.

Participant Groups

Group I: Group 6 Experimental Treatment 1 Intervention

20 mg/kg IV-repeat dosing

Group II: Group 5 Experimental Treatment 1 Intervention

5 mg/kg SC- repeat dosing

Group III: Group 4 Experimental Treatment 1 Intervention

40 mg/kg IV- single administration

Group IV: Group 3 Experimental Treatment 1 Intervention

20 mg/kg IV- single administration

Group V: Group 2 Experimental Treatment 1 Intervention

5 mg/kg SC- single administration

Group VI: Group 1 Experimental Treatment 1 Intervention

5 mg/kg IV- single administration

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

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]

VRC01LS, a modified monoclonal antibody for HIV prevention, was found to be safe and well-tolerated in a Phase I trial with 37 healthy volunteers, showing no serious adverse events and only mild side effects.

The study demonstrated that VRC01LS has a significantly extended half-life (over 4 times longer than the original VRC01), which could allow for less frequent dosing and potentially lower manufacturing costs for HIV prevention therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. Gaudinski, MR., Coates, EE., Houser, KV., et al.[2022]

In a study involving HIV-1-infected individuals, a single infusion of the monoclonal antibody VRC01 significantly reduced plasma viremia in untreated subjects, demonstrating its potential as a therapeutic agent against HIV-1.

However, in ART-treated individuals with undetectable viral loads, VRC01 did not impact the virus reservoir, indicating that while VRC01 can effectively suppress active virus in untreated patients, additional strategies may be needed for those already on antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Lynch, RM., Boritz, E., Coates, EE., et al.[2022]

VRC01, an HIV-1 broadly neutralizing antibody, was found to be safe and well tolerated in a study involving 88 healthy participants, with no serious adverse events reported after multiple doses administered either intravenously or subcutaneously.

The antibody maintained effective serum concentrations capable of neutralizing most HIV strains and demonstrated various anti-HIV activities, such as capturing HIV virions and mediating phagocytosis, indicating its potential for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial. Mayer, KH., Seaton, KE., Huang, Y., et al.[2020]

The phase 1 clinical trial of the monoclonal antibody CAP256V2LS in 42 HIV-negative women showed that it was safe, with no serious adverse events or dose-limiting toxicities reported, indicating a favorable safety profile for further testing.

Common mild side effects included headaches and nausea after intravenous administration, and headaches, chills, and fatigue after subcutaneous administration, but these were manageable and did not prevent participants from completing the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of escalating doses of neutralising monoclonal antibody CAP256V2LS administered with and without VRC07-523LS in HIV-negative women in South Africa (CAPRISA 012B): a phase 1, dose-escalation, randomised controlled trial. Mahomed, S., Garrett, N., Capparelli, EV., et al.[2023]

The phase 1 clinical trial of the monoclonal antibody VRC07-523LS, involving 26 healthy HIV-1-negative adults, demonstrated that it is safe and well tolerated, with no serious adverse events reported.

VRC07-523LS showed mild to moderate side effects, such as malaise and headache, indicating its potential as a strong candidate for HIV-1 prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Gaudinski, MR., Houser, KV., Doria-Rose, NA., et al.[2020]

Monoclonal antibodies targeting HIV show potential as new treatment options, especially against drug-resistant strains, as recent trials and lab studies indicate their clinical promise.

The main challenge remains in developing antibody therapies that provide long-lasting effectiveness, low toxicity, and a reduced risk of the virus developing resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-based inhibitors of HIV infection. Choudhry, V., Zhang, MY., Dimitrova, D., et al.[2019]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. [2022]

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

Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. [2022]

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

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of escalating doses of neutralising monoclonal antibody CAP256V2LS administered with and without VRC07-523LS in HIV-negative women in South Africa (CAPRISA 012B): a phase 1, dose-escalation, randomised controlled trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Antibody-based inhibitors of HIV infection. [2019]