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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new antibody treatment that might help prevent HIV infections. Researchers aim to determine if CAP256J3LS (also known as VRC-HIVMAB0121-00-AB) is safe for use in healthy individuals. Participants will receive either a subcutaneous injection or an IV drip, with doses ranging from low to high. This trial suits individuals aged 18 to 60 who are generally healthy without major medical issues. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

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.

Is there any evidence suggesting that CAP256J3LS is likely to be safe for humans?

Research has shown that the antibody treatment CAP256J3LS is being tested for safety in humans. This treatment uses antibodies, proteins that help fight viruses like HIV.

In earlier studies, participants received varying doses of CAP256J3LS to observe their body's reactions. The doses started small and increased gradually to ensure safety. These studies found that most participants tolerated the treatment well, experiencing no major side effects.

Any side effects were closely monitored. Common side effects included redness or swelling at the injection site. Participants also tracked their temperature and any symptoms following the treatment.

The current trial is in its early stages, primarily focusing on assessing the treatment's safety. Since the FDA has not yet approved CAP256J3LS for any condition, all results undergo careful review to ensure its safety for broader use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard HIV treatments, which often involve daily oral medications like antiretrovirals, the VRC-HIVMAB0121-00-AB antibody treatment offers a unique approach by using monoclonal antibodies to directly target and neutralize the HIV virus. This treatment is administered either intravenously or subcutaneously, which could potentially offer more flexibility and convenience in dosing. Researchers are particularly excited about its potential for longer-lasting effects with possibly fewer doses required, which could significantly improve adherence and quality of life for patients. Additionally, by targeting the virus differently, it could work in synergy with existing treatments, providing a more robust defense against HIV.

What evidence suggests that this antibody treatment might be an effective treatment for HIV?

Research has shown that CAP256J3LS, a treatment using antibodies, might help stop HIV infections. Antibodies are proteins that find and disable viruses like HIV. Early results from similar treatments have successfully prevented HIV-1 infections. CAP256J3LS is a special type of antibody that can attach to two different parts of the virus, potentially making it more effective at stopping HIV. Although this method is new, early studies suggest it could be promising for preventing or treating HIV. Participants in this trial will receive different dosages and administration methods of CAP256J3LS to evaluate its effectiveness and safety. ^{1 3 5 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?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06585891?cond=%22Viral%20Infectious%20Disease%22&intr=%22Antibodies,%20Bispecific%22&viewType=Table&rank=6

Study of a Human Bispecific Antibody VRC-HIVMAB0121- ... 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 ...

2. niaid.nih.gov niaid.nih.gov/clinical-trials/study-human-bispecific-hiv-antibody-cap256j3ls-healthy-adults

Study of a Human Bispecific HIV Antibody (CAP256J3LS) in ... This is a study of an experimental product called CAP256J3LS. This study will provide more information about prevention or treatment of human immunodeficiency ...

3. withpower.com withpower.com/trial/phase-1-human-immunodeficiency-virus-hiv-infections-8-2024-31900

Antibody Treatment for HIV · Info for Participants What data supports the effectiveness of the drug VRC-HIVMAB0121-00-AB, CAP256J3LS for treating HIV? ... HIV-uninfected adults: Results of a phase 1 randomized ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/19420862.2023.2165390

Bispecific antibody CAP256.J3LS targets V2-apex and ... AMP clinical studies of VRC01 demonstrate the ability of passively delivered antibodies to prevent HIV-1 infection, but prevention by VRC01 requires a ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-1-human-bispecific-antibody-vrc-hivmab0121-00-ab-cap256j3ls-administered-trial-nct06585891

Study of a Human Bispecific Antibody VRC-HIVMAB0121 ... Benefits: Participants will not directly benefit from the study but will contribute to the development of a potential new treatment or prevention method for HIV ...

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=001965-I&&query=Site

Protocol Details 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 ...

7. trial.medpath.com trial.medpath.com/clinical-trial/5cc6db6b3b8aab79/nct03783130-vrc-018-hiv-1-vaccine-trial

Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine ... A dose escalation evaluation occurred to ensure the safety data supported proceeding to the higher dose. Participants were evaluated for safety and immune ...