3BNC117-LS + 10-1074-LS for HIV

Recruiting at 1 trial location

Overseen By Catherine A Seamon, 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: Corticosteroids, Chemotherapy

Disqualifiers: AIDS, Hepatitis B/C, Autoimmune, others

Compensation: Varies

Number of Visits: 5

Duration: 40 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two experimental drugs, 3BNC117-LS and 10-1074-LS, to determine if they can safely reduce the amount of HIV hiding in the body. This reduction could allow people with HIV to maintain health with less medication. People on antiretroviral therapy (ART) often experience virus resurgence if they stop their medication, so these drugs might offer a way to manage HIV with fewer side effects. The trial suits individuals aged 18 to 70 who have been on ART and have HIV levels under control. Participants will receive either the study drugs or a placebo (inactive substance) through a series of infusions. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you must continue your antiretroviral therapy (ART) as part of the study.

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

Research shows that treatments like the combination of 3BNC117-LS and 10-1074-LS have generally been well tolerated. For example, a study with similar antibodies found no serious side effects. This suggests that the combination of 3BNC117-LS and 10-1074-LS might also be safe. However, since this trial is in its early stages, researchers are still learning about its full safety. Participants in early trials help researchers understand more about possible side effects and how the treatment works in the body. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 3BNC117-LS and 10-1074-LS for HIV because these treatments use monoclonal antibodies, which are different from the standard antiretroviral therapies. Unlike current treatments that require daily pills to manage the virus, these antibodies could potentially offer longer-lasting effects with fewer doses. By targeting specific proteins on the HIV virus, 3BNC117-LS and 10-1074-LS aim to neutralize the virus more effectively, which might also reduce the chance of resistance developing. This approach could lead to a new way of managing HIV with less frequent treatments and potentially improved outcomes.

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

In this trial, participants will receive either a combination of 3BNC117-LS and 10-1074-LS or a placebo. Research has shown that the combination of 3BNC117-LS and 10-1074-LS, which are special proteins called broadly neutralizing antibodies (bNAbs), may help lower HIV levels. These proteins directly attack the virus, helping to control its spread. In past studies, similar proteins successfully kept HIV levels low in people. Although researchers are still learning about 3BNC117-LS and 10-1074-LS specifically, early results suggest they can effectively reduce the virus in the body. By targeting the hidden places where HIV resides, these treatments aim to control HIV, possibly even without the need for constant medication. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael C Sneller, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Adults aged 18-70 with HIV on ART, having CD4+ T cell counts >300 cells/mcL and undetectable viral loads for at least 96 weeks. They must be able to consent, follow study procedures, not have significant health issues besides HIV, no hepatitis B or C infection, and agree to use effective contraception.

Inclusion Criteria

Ability to provide informed consent

I am willing and able to follow all study procedures for its entire duration.

Current CD4+ T cell counts > 300 cells/mcL

Exclusion Criteria

I have not had an AIDS-defining illness in the last 3 years.

Laboratory abnormalities in the parameters listed below: Absolute neutrophil count < 1,000 cells/microliter, Hemoglobin < 10 gm/dL, Platelet count < 100,000 cells/microliter, ALT > 1.5 x ULN, AST > 1.5 x ULN, Total bilirubin > 1.5 x ULN, Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m^2

I have not received any non-HIV vaccines in the last 2 weeks.

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 three intravenous infusions of 3BNC117-LS and 10-1074-LS or placebo at weeks 0, 20, and 40

40 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 weeks

1 visit every 10 weeks

Leukapheresis

Participants undergo leukapheresis up to 4 more times during the study

Throughout

What Are the Treatments Tested in This Trial?

Interventions

• 10-1074-LS
• 3BNC117-LS
• Sterile Saline

Trial Overview The trial tests if two drugs (3BNC117-LS and 10-1074-LS) can safely reduce the number of HIV-infected blood cells in people on ART compared to a saline placebo. Participants will receive doses through an IV three times over the course of the study with regular follow-ups.

How Is the Trial Designed?

Group I: 3BNC117-LS and 10-1074-LS Experimental Treatment 2 Interventions

Participants will receive three intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10-1074-LS (dosed at 10 mg/kg) at weeks 0, 20 and 40.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive three intravenous infusions of placebo (Sterile Saline) at weeks 0, 20 and 40.

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

In a study involving 10,043 treatment-naive patients with HIV-1, the 2-drug regimen of dolutegravir and lamivudine (DTG+3TC) showed similar efficacy in achieving viral suppression at 48 weeks compared to traditional 3-drug regimens, with significant superiority over efavirenz-based treatments.

Safety outcomes, including adverse events and CD4 cell count changes, were broadly similar between DTG+3TC and the other regimens, indicating that DTG+3TC is a safe and effective alternative to more complex treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients. Radford, M., Parks, DC., Ferrante, S., et al.[2020]

In a study of 70 treatment-naive HIV-infected adults over 52 weeks, three different triple combination therapies showed similar efficacy in reducing viral load and increasing CD4+ T-cell counts, indicating that all combinations are effective options for treatment.

Despite some patients experiencing adverse effects like rash and neuropathy, there were no significant differences in safety or efficacy among the treatment groups, suggesting that the choice of nucleoside reverse transcriptase inhibitor backbone does not impact the overall effectiveness of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study. French, M., Amin, J., Roth, N., et al.[2019]

In a study of 457 HIV-infected patients, both treatment regimens, EVG/c/FTC/TAF and DTG/ABC/3TC, showed improvements in serum creatinine levels over 120 weeks, indicating good renal safety profiles for both therapies.

No significant differences in renal events were observed between the two treatment groups, and the main reason for discontinuation of treatment was similar adverse events, suggesting comparable safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal profile of patients treated with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine: 120-week results from a real-world cohort. Rotea-Salvo, S., Martínez-Pradeda, A., Fernández-Oliveira, C., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

In a study of 307 antiretroviral-experienced HIV-1-infected individuals, the 1-year probability of virological failure on an ABC + TDF regimen was 34%, with higher failure rates linked to the absence of a potent cART regimen and a greater number of prior treatments.

For patients starting therapy with a viral load ≤400 copies/ml, the virological failure rate was lower at 17%, indicating that initial viral load and treatment history significantly influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of antiretroviral regimens containing abacavir with tenofovir in treatment-experienced patients: predictors of virological response and drug resistance evolution in a multi-cohort study. Di Giambenedetto, S., Torti, C., Prosperi, M., et al.[2021]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

Bictegravir (BIC) combined with emtricitabine (FTC) and tenofovir alafenamide (TAF) in the fixed-dose regimen Biktarvy® has been shown to be as effective as other leading HIV treatments, making it a strong option for initial and long-term therapy.

Biktarvy® has a high barrier to drug resistance and limited drug-drug interactions, which enhances its safety profile and makes it a recommended choice in recent HIV treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. De Clercq, E., Zhang, Z., Huang, J., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

In a study of 50 patients with HER2-negative metastatic breast cancer, the combination therapy of nivolumab, bevacizumab, and paclitaxel did not show significant differences in progression-free survival (PFS) or overall survival (OS) based on PD-L1 expression levels in tumor tissues.

Despite a decrease in vascular endothelial growth factor (VEGF)-A levels after treatment, there was no significant correlation between VEGF-A levels and PFS, indicating that VEGF-A may not serve as a reliable biomarker for treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data of programmed death-ligand 1 expression and VEGF: Nivolumab, bevacizumab and paclitaxel For HER2-negative metastatic breast cancer. Ozaki, Y., Tsurutani, J., Mukohara, T., et al.[2022]

The combination of the FRα vaccine TPIV200 and the PD-L1 inhibitor durvalumab was well tolerated in 27 patients with advanced platinum-resistant ovarian cancer, showing a low grade 3 toxicity rate of 18.5%.

While the overall response rate was low (3.7% partial response and 33.3% stable disease), the median overall survival was notably long at 21 months, suggesting potential benefits from this immunotherapy approach in a heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Zamarin, D., Walderich, S., Holland, A., et al.[2021]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

In a study involving 614 patients with advanced triple-negative breast cancer, the SP142 assay identified 46.4% of patients as PD-L1 positive, while the SP263 and 22C3 assays identified significantly higher rates of 74.9% and 73.1%, respectively, indicating that different assays can yield varying results in PD-L1 positivity.

The clinical efficacy of atezolizumab plus nab-paclitaxel was primarily observed in patients who were double-positive for SP142 and either SP263 or 22C3, suggesting that the SP142 assay may be more predictive of treatment benefit compared to the other assays, despite the latter identifying more patients as PD-L1 positive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. Rugo, HS., Loi, S., Adams, S., et al.[2023]

Bamlanivimab (BAM) has a higher number of adverse event signals compared to bamlanivimab/etesevimab (BAM/ETE), with specific risks like atrial fibrillation and tachycardia associated with BAM but not BAM/ETE.

While BAM/ETE is generally considered safe, potential safety signals such as acute respiratory failure and infusion-related reactions have been identified and warrant long-term monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database. Zhao, Y., Wang, H., Zhang, Q., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05729568

NCT05729568 | A Study of Teropavimab and Zinlirvimab in ... The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab ...

2. gileadclinicaltrials.com gileadclinicaltrials.com/study?id=GS-US-536-5816

Study to Evaluate the Safety and Efficacy of Teropavimab ... The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S235230182300293X

Safety of teropavimab and zinlirvimab with lenacapavir ... Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events.

4. askgileadmedical.com askgileadmedical.com/docs/conference/Ogbuagu_CROI2025_oral_LEN+TAB+ZAB%20Ph2%20W26@pdf

Efficacy and Safety of Lenacapavir, Teropavimab, and ... ... teropavimab; ZAB, zinlirvimab. {Extension Phase}. Primary Outcome (Efficacy): HIV-1 RNA ≥50 copies/mL at Week 26 per FDA snapshot algorithm.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12245405/

Safety of teropavimab and zinlirvimab with lenacapavir once ... Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and ...