Budigalimab + ABBV-382 for HIV/AIDS

Recruiting at 89 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must be taking: Antiretroviral therapy

Must not be taking: Long-acting antiretrovirals

Disqualifiers: CD4+ nadir <= 200, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

163 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing two new drugs, Budigalimab and ABBV-382, to treat HIV. It involves adults with stable HIV who will pause their usual treatment. The goal is to see if these new drugs can control the virus better.

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

Yes, you will need to stop your antiretroviral medications for 112 weeks or until specific criteria are met to restart them. This is called an analytical treatment interruption (ATI).

Will I have to stop taking my current medications?

Yes, participants will need to stop their antiretroviral medications for 112 weeks or until they meet specific criteria to restart them. This is part of the study's analytical treatment interruption (ATI) process.

What safety data is available for Budigalimab + ABBV-382 in HIV/AIDS treatment?

The provided research does not contain specific safety data for Budigalimab + ABBV-382 or its other names (ABBV-382, ABBV 1882, Budigalimab, ABBV-181). The studies mentioned focus on other antiretroviral drugs and treatments, such as lopinavir/ritonavir, telbivudine, nevirapine, and evolocumab, but do not address Budigalimab + ABBV-382. ^{1 2 3 4 5}

Is the drug Budigalimab a promising treatment for HIV/AIDS?

Yes, Budigalimab is a promising drug for HIV/AIDS because it is part of a new generation of antibodies that can effectively reduce the virus in the body. These antibodies have shown potential in preventing infection and controlling the virus, making them a valuable option for HIV treatment. ^{6 7 8 9 10}

What makes the drug Budigalimab + ABBV-382 unique for treating HIV/AIDS?

Budigalimab + ABBV-382 is unique because it combines two components that may work together to enhance the immune response against HIV, potentially offering a new approach compared to traditional antiretroviral therapies. This combination could provide a novel mechanism of action by utilizing antibodies to target the virus, which might help in reducing viral load and limiting the emergence of resistant strains. ^{6 7 8 9 10}

What data supports the idea that Budigalimab + ABBV-382 for HIV/AIDS is an effective drug?

The available research does not provide specific data on the effectiveness of Budigalimab + ABBV-382 for HIV/AIDS. The studies focus on drug resistance in HIV treatments and do not mention Budigalimab + ABBV-382. Therefore, there is no direct evidence from the provided information to support the effectiveness of this drug for HIV/AIDS. ^{11 12 13 14 15}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults living with HIV on stable ART for at least a year, with CD4+ T cell counts >= 500 cells/μL and undetectable viral load for 6 months can join. They must be in good health as determined by medical exams. Those with significant health risks, a history of low CD4+ counts (<=200 cells/μL), or other conditions that may risk their safety or study integrity cannot participate.

Inclusion Criteria

Negative human immuno-deficiency virus (HIV)-2 antibody (Ab)

Participant must have plasma HIV-1 ribonucleic acid (RNA) below the lower limit of quantitation (LLOQ) at screening and for at least 6 months prior to screening

I have been on HIV medication for over a year and my current treatment does not include NNRTIs.

Exclusion Criteria

Known history of medical disorders (other than HIV-1 infection) that, in the opinion of the investigator, might expose the participant to undue risk of harm, confound study outcomes or prevent the participant from completing the study.

Clinically significant medical disorders per investigator's assessment that might expose the participants to undue risk of harm, confound study outcomes, or prevent the participant from completing the study.

History of cluster of differentiation 4 (CD4+) T cell nadir of <= 200 cells/μL during chronic HIV infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive 4 doses of intravenous (IV) budigalimab or placebo combined with 3 doses of IV ABBV-382 or placebo over an 8 week dosing period

8 weeks

Regular visits at a hospital or clinic

Treatment Part 2

Eligible participants receive 4 doses of open-label subcutaneous (SC) Budigalimab over a 6 week dosing period

6 weeks

Regular visits at a hospital or clinic

Analytical Treatment Interruption (ATI)

Participants undergo a closely monitored ART interruption for up to 112 weeks or until meeting specific criteria to restart antiretroviral medications

Up to 112 weeks

Regular visits with options for virtual or home health visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 112 weeks

Regular visits with options for virtual or home health visits

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-382
• Budigalimab

Trial Overview The trial is testing Budigalimab and ABBV-382, potential new treatments for HIV. Participants will stop their usual ART and receive either the investigational drugs or placebos via IV over an 8-week period, followed by monitoring without ART for up to 52 weeks to assess changes in disease activity and drug behavior in the body.

How Is the Trial Designed?

Group I: Arm F: Budigalimab Dose B Experimental Treatment 1 Intervention

Participants will receive open-label budigalimab Dose B on Day 1 and Weeks 2, 4, and 6 (Note, no ABBV-382 or placebo will be administered).

Group II: Arm E: Budigalimab Dose A + ABBV-382 Dose A Experimental Treatment 2 Interventions

Participants will receive budigalimab Dose A on Day 1 and Weeks 2, 4, and 6 in combination with ABBV-382 Dose A on Day 1 and Weeks 4 and 8.

Group III: Arm D: Budigalimab Dose A + ABBV-382 Dose B Experimental Treatment 2 Interventions

Participants will receive budigalimab Dose A on Day 1 and Weeks 2, 4, and 6 in combination with ABBV-382 Dose B on Day 1 and Weeks 4 and 8.

Group IV: Arm C: ABBV-382 Dose A Experimental Treatment 2 Interventions

Participants will receive budigalimab placebo on Day 1 and Weeks 2, 4, and 6 in combination with ABBV-382 Dose A on Day 1 and Weeks 4 and 8.

Group V: Arm B: Budigalimab Dose A Experimental Treatment 2 Interventions

Participants will receive budigalimab Dose A on Day 1 and Weeks 2, 4, and 6 in combination with ABBV-382 matching placebo Day 1 and Weeks 4 and 8.

Group VI: Arm A: Placebo Placebo Group 2 Interventions

Participants will receive budigalimab placebo on Day 1, and Weeks 2, 4, and 6 in combination with ABBV-382 matching placebo on Day 1 and Weeks 4 and 8.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a study of 34 treatment-experienced individuals with HIV-1 subtype C, 32% exhibited drug resistance mutations (DRMs) to integrase inhibitors like dolutegravir (DTG), particularly among those previously treated with raltegravir (RAL).

Among those with DRMs, a significant portion (64%) remained virologically suppressed, but individuals with extensive resistance mutations, especially those with 4-class DRMs, faced poorer health outcomes, highlighting the importance of regular viral load monitoring and genotypic resistance testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. Seatla, KK., Maruapula, D., Choga, WT., et al.[2023]

In a study of 601 treatment-experienced HIV-1 patients, high levels of drug resistance were found, with 84% showing resistance to nucleoside reverse transcriptase inhibitors and 51% to protease inhibitors, indicating a significant challenge in treatment.

Specific mutations, such as T215F and multiple protease substitutions, were linked to increased risks of disease progression, highlighting the importance of monitoring drug resistance to guide effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. Di Giambenedetto, S., Colafigli, M., Pinnetti, C., et al.[2008]

In a study of eleven new HIV patients experiencing treatment failure after 6 months of first-line antiretroviral therapy, all ten successfully sequenced plasma samples showed resistance to at least one antiretroviral drug, highlighting a significant issue of drug resistance in this population.

The most common resistance was found against lamivudine (90%), tenofovir (83%), nevirapine (100%), and efavirenz (100%), while no resistance to zidovudine was detected, indicating the need for ongoing virology monitoring and alternative treatment options for patients with virologic failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV Drug Resistance after Failure of 6 Month First-line Therapy in a Hospital: A Case Series. Kusumaningrum, A., Ibrahim, F., Yunihastuti, E., et al.[2020]

In the POTENT trial involving 39 HIV-1-infected patients with resistance to multiple protease inhibitors, both tipranavir/ritonavir (TPV/r) and darunavir/ritonavir (DRV/r) demonstrated similar short-term efficacy, with significant viral load reductions and increases in CD4+ counts by week 12.

Both treatment regimens had comparable safety profiles, with drug-related adverse events reported in 21% of TPV/r patients and 25% of DRV/r patients, suggesting that both options are viable for patients with extensive treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial. Elgadi, MM., Piliero, PJ.[2021]

In a study of 156 HIV-infected patients, those with active GB virus C (GBV-C) infection showed significant improvements in HIV disease progression and lower mortality rates before the introduction of highly active antiretroviral therapy (HAART).

However, with the advent of HAART, the previously observed benefits of GBV-C positivity on morbidity and mortality in HIV patients diminished, suggesting that modern treatments have changed the dynamics of this co-infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a 20-year follow-up study. Ernst, D., Greer, M., Akmatova, R., et al.[2014]

The SCOLTA project has enrolled 1184 patients to monitor adverse reactions to new antiretroviral drugs, with a significant focus on lopinavir/ritonavir (LPV/r), which reported 73 out of 100 severe adverse events (grades III and IV).

The rate of adverse events in the LPV/r cohort was 14.2 per 100 person-years, indicating that this system provides valuable real-time data for assessing the safety and long-term toxicity of antiretroviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Italian approach to postmarketing monitoring: preliminary results from the SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) project on the safety of lopinavir/ritonavir. Bonfanti, P., Martinelli, C., Ricci, E., et al.[2022]

In a study of 105 patients treated with telbivudine for hepatitis B, 5 experienced serious adverse reactions, primarily myalgia and general weakness, indicating a potential risk associated with this medication.

The risk of adverse reactions was heightened in patients receiving combination therapy with interferon or other nucleoside analogues, especially at higher doses, although the exact biological mechanism behind these reactions remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features of adverse reactions associated with telbivudine. Zhang, XS., Jin, R., Zhang, SB., et al.[2021]

In a study of 703 HIV-positive pregnant women treated with nevirapine-containing antiretroviral therapy, the incidence of severe adverse reactions was low, with hepatotoxicity at 6.5%, skin rashes at 2.4%, and Stevens-Johnson syndrome at 1.1%.

The treatment was effective, as 78.6% of women achieved a viral load of less than 1000 HIV-1 RNA copies/mL after 2 months, and CD4 cell counts increased significantly, indicating that nevirapine regimens are safe and effective for managing HIV in pregnant women in African settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. Marazzi, MC., Germano, P., Liotta, G., et al.[2022]

The BEIJERINCK study is a randomized, double-blind, placebo-controlled trial involving 464 people living with HIV and hypercholesterolemia, assessing the safety and efficacy of evolocumab, a PCSK9 inhibitor, in lowering LDL cholesterol levels.

This study is significant as it targets a high-risk population for atherosclerotic cardiovascular disease, with many participants unable to tolerate high-intensity statins, thus exploring a new treatment option for managing cholesterol in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics. Boccara, F., Kumar, P., Caramelli, B., et al.[2021]

HIV protease inhibitors are effective in combination antiretroviral therapy but are associated with significant toxicity, including common adverse events like diarrhea and elevated liver enzymes.

Due to their metabolism by the hepatic cytochrome P450 system, protease inhibitors can lead to numerous drug-drug interactions, which is particularly important for patients needing additional treatments for conditions like tuberculosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of HIV protease inhibitors: clinical considerations. Boesecke, C., Cooper, DA.[2009]

A novel human monoclonal antibody (C37) targeting the gp41 glycoprotein of HIV-1 was developed from B-cells of an HIV-positive patient, showing high affinity binding to the gp41 protein, which is crucial for HIV's ability to infect cells.

The study suggests that IgM antibodies like C37 could be effective in passive immunotherapy against HIV due to their unique pentameric structure and strong complement activation capabilities, making them promising candidates for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a novel human anti-HIV-1 gp41 IgM monoclonal antibody designated clone 37. Cao, C., Bai, Y., Holloway, MJ., et al.[2007]

In a phase II trial involving 158 early-stage HIV+ volunteers, the idiotype vaccine using mAb 13B8.2 was well tolerated, primarily causing local side effects, indicating its safety for use in this population.

The treatment led to a significant increase in HIV-1 neutralization and specific anti-viral immune responses, suggesting that the vaccine could positively influence the progression of HIV disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of anti-CD4 idiotype vaccination in HIV positive volunteers. Schedel, I., Sutor, GC., Hunsmann, G., et al.[2019]

In a phase 1b clinical trial involving seven HIV-1 viremic individuals, a combination of two potent broadly neutralizing antibodies (bNAbs) was well-tolerated and led to a significant average reduction in HIV-1 viral load by 2.05 log10 copies per ml for three months in those with sensitive viruses.

Importantly, none of the participants developed resistance to both antibodies, suggesting that this combination therapy may effectively limit the emergence of drug-resistant viral variants, warranting further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Bar-On, Y., Gruell, H., Schoofs, T., et al.[2022]

The first-in-man clinical trial of the antibody 3BNC117 showed it was safe and well tolerated in both uninfected and HIV-1-infected individuals, indicating its potential for human use.

A single infusion of 3BNC117 significantly reduced viral load in HIV-1-infected individuals by 0.8-2.5 log10, with effects lasting for 28 days, suggesting its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Caskey, M., Klein, F., Lorenzi, JC., et al.[2022]

The bifunctional antibody (BFA) combining anti-CD3 and anti-HIV-1 gp41 fragments effectively inhibited HIV-1 in cultured lymphoblasts, showing promise as a treatment for HIV-infected patients.

BFA-TLBC was able to eliminate latently infected cells after prolonged cocultivation, suggesting it could help eradicate cells that remain resistant to standard antiretroviral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elimination of latently HIV-1-infected cells by lymphoblasts armed with bifunctional antibody. Yin, S., Okada, N., Okada, H.[2019]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. [2023]

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

Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. [2008]

3. Indonesia pubmed.ncbi.nlm.nih.gov

HIV Drug Resistance after Failure of 6 Month First-line Therapy in a Hospital: A Case Series. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a 20-year follow-up study. [2014]

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

An Italian approach to postmarketing monitoring: preliminary results from the SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) project on the safety of lopinavir/ritonavir. [2022]

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

Clinical features of adverse reactions associated with telbivudine. [2021]

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

Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. [2022]

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

Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics. [2021]

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

Toxicity of HIV protease inhibitors: clinical considerations. [2009]

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

Characterization of a novel human anti-HIV-1 gp41 IgM monoclonal antibody designated clone 37. [2007]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Phase II study of anti-CD4 idiotype vaccination in HIV positive volunteers. [2019]

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

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. [2022]

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

Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. [2022]

15. Australia pubmed.ncbi.nlm.nih.gov

Elimination of latently HIV-1-infected cells by lymphoblasts armed with bifunctional antibody. [2019]