Budigalimab + ABBV-382 for HIV/AIDS
Recruiting in Palo Alto (17 mi)
+89 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: AbbVie
Prior Safety Data
Trial Summary
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).
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.
12345What 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.
678910Is 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.
1112131415Eligibility Criteria
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.
+2 more
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.
Participant Groups
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.
6Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm F: Budigalimab Dose BExperimental Treatment1 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 AExperimental Treatment2 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 BExperimental Treatment2 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 AExperimental Treatment2 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 AExperimental Treatment2 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: PlaceboPlacebo Group2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill Univ Clinical Research /ID# 256992Montreal, Canada
East Carolina University - Brody School of Medicine /ID# 257544Greenville, NC
Toronto General Hospital /ID# 256994Toronto, Canada
Spectrum Health Vancouver /ID# 260791Vancouver, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
References
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana. [2023]There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.
Genotypic resistance profile and clinical progression of treatment-experienced HIV type 1-infected patients with virological failure. [2008]We explored the relationship between HIV-1 drug resistance in treatment-experienced patients and disease progression in a cohort of patients undergoing resistance testing to guide treatment decisions. A total of 601 treatment-failing individuals tested for genotypic HIV-1 drug resistance between 1998 and 2004 were selected. At genotypic testing, median HIV-1 RNA levels and CD4 counts were 3.8 log copies/ml and 293 cells/mul, respectively; 84% had resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs), 42% had resistance mutations to non-NRTIs, 51% had major resistance mutations to protease inhibitors (PI), 12% had no major resistance mutations to any drug class, 22% had mutations to one class, 42% had mutations to two classes, and 23% had mutations to three classes. During a follow-up of 714.7 patients/year, 80 patients showed an AIDS-defining event or died. In multivariable models adjusting for prior AIDS, baseline CD4 counts, HIV-1 RNA, and calendar year, viral resistance variables associated with increased hazards of clinical progression were the presence of reverse transcriptase substitution T215F (p = 0.002) and the presence of three or more protease substitutions among L33F/I/V, V82A/F/L/T, I84V, and L90M (p = 0.003). Resistance to three drug classes remained independently predictive of clinical progression only when calendar year was not used as an adjustment factor. Prevention and treatment of multiple drug class resistance are clinical priorities for HIV-infected patients. In recent years, improved treatment options may have helped in reducing part of the resistance-associated clinical progression.
HIV Drug Resistance after Failure of 6 Month First-line Therapy in a Hospital: A Case Series. [2020]This is the first report of HIV drug resistance in RSUPN Dr. Cipto Mangunkusumo. We tested We reviewed eleven new cases of HIV patients who had virologic failure after 6 months first-line antiretroviral therapy. With the sequencing method, analysis of gene mutations encoded HIV drug resistance. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. Of ten plasma samples that were successfully amplified and sequenced, all samples were resistant to at least one antiretroviral drug. Genotypic resistance towards the antiretroviral drugs being used was observed in lamivudine (90%), tenofovir (83%), nevirapine (100%) dan efavirenz (100%). It is interesting that no zidovudine resistance were found, including in four patients receiving zidovudine in their HAART. The common NRTI mutations were M184VI and K65R, while NNRTI mutations were Y181CFGVY, K103N, A98AG, E138GQ and G190AGS. No mayor PI mutations were found. Based on these findings, we supports the need for appropriate virology monitoring and HIV drug resistance survey in clinical practice and access to drug options in case of virology failure.
Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial. [2021]The POTENT trial compared the safety and efficacy of tipranavir/ritonavir (TPV/r) to darunavir/ritonavir (DRV/r), each with an optimized background regimen (OBR) in triple-class experienced HIV-1-infected patients with resistance to more than one protease inhibitor (PI).
Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a 20-year follow-up study. [2014]The impact of coexisting GB virus C (GBV-C) infection on the clinical course of HIV infection remains controversial. Early data from HIV-1 infected patients attending the Hannover Medical School in 2001 suggested prognostic benefit in GBV-C viraemic patients. The aim of this study was to evaluate patterns in long-term mortality and morbidity outcomes in this cohort. The impact of the introduction of antiretroviral therapy (ART) on the perceived benefits of GBV-C viraemia was subsequently investigated.
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]The SCOLTA project (Surveillance Cohort Long-term Toxicity Antiretrovirals) is a system for online surveying of adverse reactions to recently commercialized antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions arising during any antiretroviral treatment (available at: http://www.cisai.info). To date, 25 Italian departments of infectious diseases have participated at the project. The New Drugs Project is a prospective, multicenter, observational pharmacovigilance study involving 1 cohort of patients for each new drug. All patients who were consecutively started on lopinavir (LPV), tenofovir (TDF), peginterferon (IFN), atazanavir (ATZ), enfuvirtide (T-20), and tipranavir (TPV) were enrolled. All grade III or IV adverse events (according to the AIDS Clinical Trials Group definitions) are reported on the web site. The Unexpected Events Project identifies unexpected adverse reactions during treatment and reports them. This paper presents the preliminary findings for the New Drugs Project. Between October 1, 2002, and March 30, 2004, 1184 patients were enrolled. The lopinavir/ritonavir (LPV/r) cohort comprises 703 patients, the TDF cohort 585, IFN 35, ATZ 95, T-20 10, and TPV 8. So far 100 grades III and IV adverse events have been reported, 73 in the LPV/r group. In this cohort the rate of adverse events per 100 person-years was 14.2 on the basis of all patients treated, 9.8 for treatment-naive patients, and 15 for treatment-experienced patients. These findings, though preliminary, show that this data collection method gives timely real-life information from which to assess the impact of short- and long-term toxicity of new antiretroviral drugs.
Clinical features of adverse reactions associated with telbivudine. [2021]To analyze the clinical features and risk factors of adverse reactions associated with telbivudine.
Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. [2022]To assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy.
Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics. [2021]People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia.
Toxicity of HIV protease inhibitors: clinical considerations. [2009]To review recent studies reporting toxicity, adverse events, side effects, and drug-drug interactions related to the use of HIV protease inhibitors, with particular focus on possible clinical implications.
Characterization of a novel human anti-HIV-1 gp41 IgM monoclonal antibody designated clone 37. [2007]Human monoclonal antibodies (HuMAbs) demonstrate great potential for passive immunotherapy against HIV-1. The gp41 transmembrane envelope glycoprotein of HIV has an important role in the pathogenicity of AIDS and importantly displays considerably less hypervariability than the gp120 surface envelope HIV glycoprotein, which makes it particularly a better candidate for the development of passive and active immunotherapies. The general aim of this study was to develop HuMAbs to HIV surface glycoproteins and particularly gp41. Peripheral blood mononuclear cells (PBMCs) were isolated from an HIV-seropositive long-term nondisease progressing patient. B-cells from this individual were then immortalized by Epstein-Barr virus (EBV) transformation, and antibody production was stabilized by fusion of transformed cells with a heteromyeloma. Subsets of the human heterohybridomas so generated were analyzed by ELISA. The hybridoma with the highest binding by immunoassay against gp160 was further analyzed. This hybridoma, designated as clone 37 (C37), was determined to be an IgM Kappa antibody and overlapping peptides of HIV envelope proteins (derived from the MN tissue culture line adapted HIV isolate) were used to map the specific binding domain of this HuMAb. Overlapping peptides designated 2026 (SWSNKSLDDIWNN, AA614-626), and 2027 (DDIWNNMTWMQWEREIDNYT, AA621-640) within the HIV-1 gp41 transmembrane glycoprotein were demonstrated to bind to C37 indicating that the specific binding domain for the antibody was DDIWNN. High affinity binding of C37 by ELISA to recombinant gp41 was demonstrated as well. Few IgM HuMAbs against HIV have been generated and characterized. Theoretically, because of the pentameric binding nature of IgM antibodies as well as their very efficient ability to activate complement, such reagents could have potential as anti-HIV agents.
Phase II study of anti-CD4 idiotype vaccination in HIV positive volunteers. [2019]A clinical phase II trial of postinfectional idiotype vaccination was performed in early stage HIV + volunteers. The mAb 13B8.2 is directed against the CDR3-homologous CD4/D1 region implicated in HIV-gp120 binding. We have previously shown that this mAb induces HIV-gp120 cross-reactive immunity. In addition, the mAb 13B8.2 was well tolerated in a clinical phase-Ia trial. In this phase-II trial, 158 patients with 350-500 CD4+ cells/microl blood were randomised to receive either 1.2 mg of alum-precipitated mAb 13B8.2 or placebo. The mAb was well tolerated evoking predominantly local side effects. Multivariant analysis of clinical study endpoints demonstrated a significant response in the verum group (intend-to-treat analysis). Titres of HIV-1 neutralisation in vitro were raised along with HIV/gp120 antigen binding titres. Our data indicate that patients treated with the idiotype vaccine will produce an augmented specific anti-viral immune response. The vaccine might thus have a positive impact on the course of HIV disease.
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. [2022]Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants1,2. Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection3,4. Although anti-HIV-1 antibodies constitute a potential alternative to ART5,6, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants7-9. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection10-12. Here we report on a phase 1b clinical trial ( NCT02825797 ) in which two potent bNAbs, 3BNC11713 and 10-107414, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30 mg kg-1 of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log10 copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants.
Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. [2022]HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.
Elimination of latently HIV-1-infected cells by lymphoblasts armed with bifunctional antibody. [2019]The Fab' fragment of a monoclonal antibody (mAb) to CD3 and the F(ab')2 fragment of a mAb to human immunodeficiency virus 1 (HIV-1) gp41 were combined to generate a bifunctional antibody (BFA). The mAb to gp41 (IV1-4G6) has previously been shown to react with a number of HIV-1 strains and T-lymphoblastoid cells (TLBC) armed with the BFA (BFA-TLBC) effectively inhibited HIV-1 in primarily cultured lymphoblasts infected with the clinically isolated virus which was reactive to the mAb. Although BFA-TLBC could not cause cytolysis of 51Cr-labeled latently infected cells (OM-10.1) in 6 hr incubation, cocultivation of OM-10.1 cells with BFA-TLBC for 3 days or more eliminated the latently infected cells making the cells susceptible to BFA-TLBC. Therefore, BFA-TLBC may be beneficial for HIV-infected patients in eradicating latently infected cells which can not be eliminated even with highly active antiretroviral therapy (HAART).