Budigalimab + ABBV-382 for HIV/AIDS

No longer recruiting at 105 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments, Budigalimab and ABBV-382, to evaluate their effects on people living with HIV. The goal is to understand how these drugs impact the virus and the body, and to identify any side effects. Participants will join different groups, with some receiving the actual treatment and others a placebo (a non-active substance). The trial seeks individuals with stable HIV who are on antiretroviral therapy and willing to temporarily stop their current treatment under close supervision. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in HIV treatment.

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.

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

Research has shown that Budigalimab has been tested for safety and tolerability. In earlier studies, most participants did not experience serious side effects. The main focus was on safety, and results indicated it is generally well-tolerated.

For ABBV-382, studies have examined its safety in people with HIV, focusing on how the body absorbs and processes the drug. Although information on side effects is limited, the studies aimed to ensure ABBV-382 is safe for use.

Both Budigalimab and ABBV-382 remain under investigation in clinical trials, with their safety closely monitored. Since this study is in an early phase, earlier research has demonstrated sufficient safety to continue testing in humans. Prospective participants should consult their doctor about potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Budigalimab and ABBV-382 for HIV/AIDS because these treatments could offer new ways to manage the condition. Unlike the standard antiretroviral therapies that primarily target viral replication, Budigalimab is a monoclonal antibody that may help modulate the immune response, potentially offering longer-lasting effects. ABBV-382, on the other hand, might work synergistically with Budigalimab to enhance the treatment's overall effectiveness. These innovative approaches could provide alternative options for patients, especially those who are not responding well to current therapies.

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

Research has shown that budigalimab, a type of medication, might help delay the return of the virus in people with HIV. In one study, two out of eleven participants managed to control the virus without their usual HIV medication for a year and a half after taking budigalimab. This finding suggests that budigalimab could be more effective in managing HIV. In this trial, some participants will receive budigalimab alone, while others will receive it in combination with ABBV-382. Specific information about ABBV-382's effectiveness for HIV alone remains limited, but researchers are studying its safety and behavior in the body. The combination of budigalimab and ABBV-382 is still under exploration to understand their joint effect on treating HIV. ^{1 2 3 4 6}

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

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]

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]

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 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]

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 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]

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]

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 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]

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 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]

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]

Citations

1. natap.org natap.org/2023/HIV/091923_02.htm

Abbvie ABBV-382+ Budigalimab with ATI in PWH The purpose of this study is to assess change in disease activity, adverse events, tolerability, and how the drug moves through the body. Budigalimab and ABBV- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04554966

NCT04554966 | Study to Assess Adverse Events and How ... This study will evaluate how safe ABBV-382 is and how it is absorbed, distributed and eliminated from the body in adult participants with HIV-1 infection.

3. withpower.com withpower.com/trial/phase-2-acquired-immunodeficiency-syndrome-9-2023-aad44

Budigalimab + ABBV-382 for HIV/AIDS · Info for Participants 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 ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/viiv-to-trial-twice-yearly-hiv-antibody-dosing-after-phase-iib-success/

ViiV to trial twice-yearly HIV antibody dosing after Phase IIb ... The company's Phase IIb trial found the therapy, N6LS, was able to maintain viral loads below a detectable threshold.

5. diagnosticsworldnews.com diagnosticsworldnews.com/news/2024/03/20/abbvie-launches-phase-i-clinical-trial-for-abbv-1882-promising-hiv-drugs-treatment-approach

AbbVie Launches Phase I Clinical Trial for ABBV-1882 ... The approach employed by ABBV-1882 offers a promising avenue for enhancing the efficacy and tolerability of HIV treatment.

6. synapse.patsnap.com synapse.patsnap.com/drug/db408a8b79d84d6fa823a1eec64f60f3

ABBV-1882 - Drug Targets, Indications, Patents A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of Budigalimab ...