VRC07-523LS + PGT121.414.LS for HIV

Not yet recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Protease inhibitors, Integrase inhibitors

Must not be taking: Corticosteroids, Chemotherapy, others

Disqualifiers: AIDS, Malignancy, ASCVD, others

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

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using two antibodies, VRC07-523LS and PGT121.414.LS, designed to control HIV without daily medication. The goal is to evaluate the effectiveness and safety of these antibodies when participants temporarily stop their usual HIV treatment. Individuals who have maintained stable HIV treatment without interruptions for the past year and have controlled virus levels might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop my current medications for the trial?

The trial requires participants to be on a stable HIV treatment regimen (ART) for at least 12 months before starting. It doesn't specify stopping other medications, but you should discuss your current medications with the trial team to ensure they don't interfere with the study.

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

Research has shown that both PGT121.414.LS and VRC07-523LS have been tested for safety in earlier studies. For PGT121.414.LS, these studies examined how the body processes the drug and its safety in adults, showing it was generally well-tolerated without serious side effects. Another study on VRC07-523LS found it to be safe and well-tolerated at various doses and methods of administration, indicating most participants did not experience major issues.

These findings suggest both treatments have a good safety record so far. However, since the current trial is in an early stage, it aims to gather more information about their safety, indicating there is still more to learn about how these treatments work in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PGT121.414.LS and VRC07-523LS for HIV because they represent a novel approach compared to traditional antiretroviral therapies. These investigational treatments are broadly neutralizing antibodies, which work by targeting the HIV virus directly, potentially offering a new way to prevent and control infection. Unlike standard antiretroviral drugs that need to be taken daily and can have significant side effects, these antibodies could provide longer-lasting protection with fewer side effects. Additionally, this treatment approach aims to enhance the immune system's ability to fight HIV, offering hope for improved management of the condition.

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

This trial will evaluate the effectiveness of two broadly neutralizing antibodies (bNAbs), PGT121.414.LS and VRC07-523LS, in fighting HIV. Research has shown that PGT121.414.LS can strongly block the virus from infecting cells. Studies have found that VRC07-523LS is safe, well tolerated, and may work for a long time in preventing HIV. Participants in this trial will receive either PGT121.414.LS or VRC07-523LS, as these antibodies attack HIV in different ways, potentially increasing their effectiveness when used together. Early trials suggested they could help control HIV when standard treatments are temporarily stopped. These findings offer hope for using these antibodies in future HIV treatment plans. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals living with HIV who started antiretroviral therapy (ART) early after infection. Participants must be willing to interrupt their current ART under close monitoring to test new treatments.

Inclusion Criteria

Ability and willingness of participant to provide informed consent

Specific laboratory values within 60 days prior to Step 1 entry

Agreement to use highly effective contraception for women engaging in sexual activity that could lead to pregnancy

Exclusion Criteria

I have not had an AIDS-defining illness or opportunistic infection in the last 2 years.

I do not have any serious health conditions that would stop me from joining.

Breastfeeding or plans to become pregnant within the next 36 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-entry

Participants have a pre-entry visit to confirm eligibility and prepare for study entry

1 week

1 visit (in-person)

Step 1

Participants remain on ART and receive an infusion of VRC07-523LS and PGT121.414.LS

12 weeks

2 visits (in-person)

Step 2

Participants interrupt ART and receive a second infusion of VRC07-523LS, monitored for ART resumption

12 weeks

2 visits (in-person)

Step 3

Participants resume ART upon meeting criteria and are followed for viral suppression

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 98 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PGT121.414.LS
• VRC07-523LS

Trial Overview The study tests the safety and effectiveness of two human monoclonal antibodies, VRC07-523LS and PGT121.414.LS, in controlling HIV without regular ART during a monitored treatment pause.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

Group II: Arm A Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Monogram Biosciences

Collaborator

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301824002479

Safety, tolerability, pharmacokinetics, and neutralisation ... The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04212091

Study Details | NCT04212091 | Evaluating the Safety, ... This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in ...

3. hiv.lanl.gov hiv.lanl.gov/mojo/immunology/search/ab/results?id=4165

HIV Molecular Immunology Database Search In late 2022, PGT121.414.LS was in clinical safety efficacy assessment in HVTN136/HPTN092 studies. ... Previously-published neutralization data for PGT121.414.LS ...

4. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/pgt121/health-professional

PGT121 Health Professional Drug Record | NIH Investigational HIV drug information about PGT121 for health professionals: pharmacology, clinical trials, adverse events, and more.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8508778/

Clinical Trials of Broadly Neutralizing Monoclonal Antibodies ... Published data indicate that these bnAbs are safe and have a half-life ranging from 15 to 71 days. Only intravenous VRC01 has advanced to an efficacy trial, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39667379

a first-in-human, open-label, randomised controlled phase 1 trial The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults.

7. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT06517693

PGT121.414.LS Alone and in Combination With VRC07 ... The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) ...