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

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Michael C Sneller, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

Background: Antiretroviral therapy (ART) can suppress HIV to undetectable levels in people, but the virus rebounds quickly if the drug treatment is stopped; this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir (PVR). Yet lifelong ART is expensive and can lead to serious side effects over the long term. Some drugs may be more effective at reducing the PVR. Objective: To see if 2 study drugs (3BNC117-LS and 10-1074-LS) are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART. Eligibility: People aged 18 to 70 years with HIV who are on ART. Design: Participants will be screened. They will have a physical exam and blood and urine tests. They will undergo leukapheresis. Leukapheresis is a procedure where blood is drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm. The study drugs or placebo (normal saline) will be administered 3 times at 20-week intervals. The drugs will be given through a tube attached to a needle inserted into a vein in the arm. This will take 1 hour. Some participants will receive only a saline solution. They will not know if they are getting the drugs or the placebo. Participants will undergo leukapheresis up to 4 more times during the study. Participants will have follow-up visits every 10 weeks until the study ends.

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.

What data supports the idea that 3BNC117-LS + 10-1074-LS for HIV is an effective treatment?

The available research does not provide any data on the effectiveness of 3BNC117-LS + 10-1074-LS for HIV. The studies mentioned focus on treatments for different types of cancer, such as breast and ovarian cancer, and do not include information on this specific HIV treatment. ^{1 2 3 4 5}

What safety data is available for the HIV treatment 3BNC117-LS + 10-1074-LS?

The provided research does not contain safety data for the HIV treatment 3BNC117-LS + 10-1074-LS or its related names. The articles focus on the safety of nivolumab and other immune checkpoint inhibitors, as well as treatments for COVID-19, but do not address the specific HIV treatment in question. ^{6 7 8 9 10}

Is the drug 3BNC117-LS a promising treatment for HIV?

The information provided does not include any details about 3BNC117-LS or its effectiveness for treating HIV, so we cannot determine if it is promising based on the given research articles. ^{11 12 13 14 15}

Research Team

Michael C Sneller, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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.

I am between 18 and 70 years old.

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.

Trial Timeline

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

Treatment Details

Interventions

• 10-1074-LS (Monoclonal Antibodies)
• 3BNC117-LS (Monoclonal Antibodies)
• Sterile Saline (Other)

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.

Participant Groups

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+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Data of programmed death-ligand 1 expression and VEGF: Nivolumab, bevacizumab and paclitaxel For HER2-negative metastatic breast cancer. [2022]

2. England 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. [2021]

3. England 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. [2023]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

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

PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. [2023]

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

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

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

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database. [2023]

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

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]

10. United States 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. [2021]

11. England 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. [2023]

12. Germany 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. [2021]

13. England 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. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. [2023]

15. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients. [2020]