HB-502 + HB-501 for HIV
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Hookipa Biotech GmbH
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a study of HB-502 and HB-501 alternating 2-vector therapy in people living with human immunodeficiency virus (HIV) who are taking antiretroviral treatment (ART).
The benefits of available ART are short-lived and eventually there is a return of rapid HIV replication and higher viral copy number after a period of initial improvement of infection. The study treatment made of HB-502 and HB-501 is designed to train the body to recognize and fight parts from substances found in HIV.
This trial studies the safety, tolerability, and ability of HB-502 and HB-501 to stimulate an immune response against HIV in people living with HIV.
Participants will receive the study treatment by injection into the muscle every 8 weeks for a duration of 24 weeks, which is followed by another 24 weeks to continue looking closely at the safety profile and anti-HIV immune reaction after the last dose of study treatment.
Do I have to stop taking my current medications for this trial?
No, you do not have to stop taking your current antiretroviral treatment (ART). In fact, you must be on stable ART for at least 48 weeks before joining the trial.
What data supports the idea that HB-502 + HB-501 for HIV is an effective treatment?
The available research does not provide specific data on the effectiveness of HB-502 + HB-501 for HIV. Instead, it discusses other treatments like boosted darunavir plus rilpivirine, which is shown to be effective and well-tolerated for HIV suppression. Additionally, dual-therapy regimens are highlighted as promising alternatives to traditional three-drug regimens, suggesting that two-drug treatments can be effective. However, there is no direct evidence from the provided research about the effectiveness of HB-502 + HB-501 for HIV.
12345What safety data exists for HB-502 and HB-501 treatment for HIV?
The provided research does not contain any safety data for HB-502 and HB-501 treatment for HIV. The studies focus on ATR and ATM inhibitors, such as AZD6738 and M3541, in cancer treatment, which are unrelated to the HB-502 and HB-501 therapy for HIV.
678910Is the HB-502 and HB-501 alternating 2-vector therapy a promising treatment for HIV?
Yes, the HB-502 and HB-501 alternating 2-vector therapy is promising because dual therapies, like this one, can be effective and simpler than traditional treatments. They may reduce side effects, lower costs, and improve adherence to treatment, making them a valuable option for managing HIV.
411121314Eligibility Criteria
This trial is for people living with HIV who are currently on suppressive antiretroviral therapy (ART). Participants should be stable on ART, have a suppressed viral load, and meet other health criteria to ensure safety during the trial.Inclusion Criteria
I am between 18 and 65 years old.
Confirmed HIV infection as documented by medical records or confirmatory HIV testing at screening
My HIV viral load has been undetectable for at least 48 weeks.
+3 more
Exclusion Criteria
Is pregnant or breastfeeding or expecting to conceive or father children starting with the screening visit through a minimum of 12 weeks after the last dose of trial treatment
History of hypersensitivity or other contraindication to any of the components of the study interventions as determined by the Investigator
My HIV condition is beyond stage 2 according to CDC guidelines.
+14 more
Participant Groups
The study tests HB-502 and HB-501 therapies designed to boost the immune response against HIV. It compares two different dose levels of these therapies against a placebo. Participants will receive injections every 8 weeks over six months.
2Treatment groups
Experimental Treatment
Group I: HB-502 and HB-501 alternating 2-vector therapy (Dose Level 2) OR placeboExperimental Treatment2 Interventions
Intramuscular injection of HB-502 and HB-501 alternating 2-vector therapy at Dose Level 2 OR placebo every 8 weeks for 24 weeks (injections at Weeks 0, 8, 16, and 24).
Group II: HB-502 and HB-501 alternating 2-vector therapy (Dose Level 1) OR placeboExperimental Treatment2 Interventions
Intramuscular injection of HB-502 and HB-501 alternating 2-vector therapy at Dose Level 1 OR placebo every 8 weeks for 24 weeks (injections at Weeks 0, 8, 16, and 24).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women´s HospitalBoston, MA
Beth Israel Deaconness Medical Center (BIDMC)Boston, MA
Orlando Immunology Center (OIC)Orlando, FL
The Hope Clinic at Emory UniversityDecatur, GA
More Trial Locations
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Who Is Running the Clinical Trial?
Hookipa Biotech GmbHLead Sponsor
References
Highly active antiretroviral therapy and viral response in HIV type 2 infection. [2006]Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2. CD4+ cell count, HIV-2 virus load, and clinical status were found to correlate well, providing evidence that HIV-2 virus load is useful in managing treatment of patients with HIV-2 who are receiving therapy. However, HAART regimens with predicted efficacy for treatment of HIV type 1 infection are not as efficacious for treatment of HIV-2. Controlled clinical trials of HIV-2-infected patients receiving various HAART regimens are needed to provide therapeutic guidance to the medical community.
Effectiveness of boosted darunavir plus rilpivirine in patients with long-lasting HIV-1 infection: DARIL study. [2022]The combination of boosted darunavir plus rilpivirine, once daily, could be a convenient, effective and well-tolerated two-drug regimen to achieve HIV suppression in HIV-infected patients.
Virologic and immunologic responses to antiretroviral therapy among HIV-1 and HIV-2 dually infected patients: case reports from Abidjan, Côte d'Ivoire. [2009]In four of five HIV-1 and HIV-2 dually infected patients treated with efavirenz-based therapy, viral load was undetectable for HIV-1 only, with limited increase in CD4+ counts. Both viral loads were undetectable and CD4+ counts increased in one patient treated with protease inhibitor regimen. Specific guidelines for treating HIV-dually infected patients are needed that should avoid the use of non-nucleoside reverse transcriptase inhibitors.
Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere? [2021]The advent of combination antiretroviral therapy (ART) has significantly decreased AIDS-related morbidity and mortality. Nevertheless, the benefits of ART are only realized through adherence to lifelong treatment. Though contemporary antiretroviral (ARV) drugs have fewer adverse effects in comparison to older ARV drugs, many agents are associated with negative or unknown long-term effects. There is increasing evidence that two-drug (dual-therapy) regimens may be an effective alternative to the currently recommended three-drug (triple-therapy) regimens. In this review, we provide a comprehensive and critical review of recently completed and ongoing trials of dual-therapy regimens in treatment-naïve and treatment-experienced HIV-1-infected patients. We also review current HIV/AIDS society recommendations regarding dual therapy as well as future therapeutic possibilities.
Raltegravir and unboosted atazanavir dual therapy in virologically suppressed antiretroviral treatment-experienced HIV patients. [2015]Because of the favourable safety and tolerability profiles of atazanavir (ATV) and raltegravir (RAL), attention has recently turned to the use of dual ATV plus RAL therapy as a nucleoside reverse transcriptase inhibitor-sparing treatment strategy in highly antiretroviral treatment (ART)-experienced HIV-infected patients.
Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers. [2021]Radiotherapy (RT) has a central role in head and neck squamous cell carcinoma (HNSCC) treatment. Targeted therapies modulating DNA damage response (DDR) and more specific cell cycle checkpoints can improve the radiotherapeutic response. Here, we assessed the influence of ataxia-telangiectasia mutated and Rad3-related (ATR) inhibition with the ATR inhibitor AZD6738 on RT response in both human papillomavirus (HPV)-negative and HPV-positive HNSCC. We found that ATR inhibition enhanced RT response in HPV-negative and HPV-positive cell lines independent of HPV status. The radiosensitizing effect of AZD6738 was correlated with checkpoint kinase 1 (CHK1)-mediated abrogation of G2/M-arrest. This resulted in the inhibition of RT-induced DNA repair and in an increase in the percentage of micronucleated cells. We validated the enhanced RT response in HPV-negative and HPV-positive xenograft models. These data demonstrate the potential use of ATR inhibition in combination with RT as a treatment option for both HPV-negative and HPV-positive HNSCC patients.
Enhancement of non-homologous end joining DNA repair capacity confers cancer cells resistance to the novel selenophene compound, D-501036. [2021]D-501036 is a promising anti-cancer compound that exhibits potent anti-proliferative activity against various types of human cancers through the induction of double strand DNA breaks. To determine drug resistance mechanism related to this class of DNA-damaging agents, a KB-derived D-501036-resistant cell line (S4) was established. Results showed that S4 cells exhibit enhanced DNA rejoining ability as compare to KB cells, through up-regulation of the non-homologous end joining activity. In conclusion, enhancement of NHEJ activity plays important role in the development of D-501036-resistance and targeting NHEJ-related molecules maybe able to overcome drug resistance to DNA damaging agents.
pRAD50: a novel and clinically applicable pharmacodynamic biomarker of both ATM and ATR inhibition identified using mass spectrometry and immunohistochemistry. [2021]AZD0156 and AZD6738 are potent and selective inhibitors of ataxia-telangiectasia-kinase (ATM) and ataxia-telangiectasia-mutated and Rad3-related (ATR), respectively, important sensors/signallers of DNA damage.
Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors. [2022]Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.
ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib. [2023]AZD6738 (ceralasertib) is a potent and selective orally bioavailable inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. ATR is activated in response to stalled DNA replication forks to promote G2-M cell-cycle checkpoints and fork restart. Here, we found AZD6738 modulated CHK1 phosphorylation and induced ATM-dependent signaling (pRAD50) and the DNA damage marker γH2AX. AZD6738 inhibited break-induced replication and homologous recombination repair. In vitro sensitivity to AZD6738 was elevated in, but not exclusive to, cells with defects in the ATM pathway or that harbor putative drivers of replication stress such as CCNE1 amplification. This translated to in vivo antitumor activity, with tumor control requiring continuous dosing and free plasma exposures, which correlated with induction of pCHK1, pRAD50, and γH2AX. AZD6738 showed combinatorial efficacy with agents associated with replication fork stalling and collapse such as carboplatin and irinotecan and the PARP inhibitor olaparib. These combinations required optimization of dose and schedules in vivo and showed superior antitumor activity at lower doses compared with that required for monotherapy. Tumor regressions required at least 2 days of daily dosing of AZD6738 concurrent with carboplatin, while twice daily dosing was required following irinotecan. In a BRCA2-mutant patient-derived triple-negative breast cancer (TNBC) xenograft model, complete tumor regression was achieved with 3 to5 days of daily AZD6738 per week concurrent with olaparib. Increasing olaparib dosage or AZD6738 dosing to twice daily allowed complete tumor regression even in a BRCA wild-type TNBC xenograft model. These preclinical data provide rationale for clinical evaluation of AZD6738 as a monotherapy or combinatorial agent.
Dual antiretroviral therapy for HIV infection. [2017]For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.
HIV: how to manage heavily treatment-experienced patients. [2022]Although decreasing in prevalence, heavily treatment-experienced (HTE) persons with limited options for HIV treatment present unique complexities, even amongst experienced providers, as there is no single approach to successful management. HTE patients are described as those having two or less antiretroviral (ARV) classes available for use with limited fully active ARV agents within each class. A detailed understanding of the underlying processes that caused previous treatment failures, diagnostics to define resistance, resistance mechanisms and ARV pharmacology should all function in tandem to determine the next steps of clinical care. This narrative review provides an overview of the clinician approach to care, including diagnostics, approaches to regimen creation, relevant resources, and a broad array of both currently available and upcoming ARVs that may be used in regimens for HTE patients.
Efficacy and safety of switching to dolutegravir plus lamivudine versus continuing triple antiretroviral therapy in virologically suppressed adults with HIV at 48 weeks (DOLAM): a randomised non-inferiority trial. [2021]Simplified antiretroviral therapy (ART) regimens are desirable for people with HIV. We investigated the efficacy and safety of switching from triple ART to dual dolutegravir plus lamivudine therapy.
Treatment strategies for highly treatment-experienced HIV-infected patients. [2006]The management of highly treatment-experienced HIV-infected patients is often complicated by baseline antiretroviral drug resistance, patient intolerabilities, drug-drug interactions and quality-of-life issues; which are all factors that can limit the ability to construct a potent regimen. The mainstay of treatment has been to use new agents with activity against resistant virus. New agents, such as enfuvirtide and tipranavir/ritonavir, have shown promising results in highly active antiretroviral treatment regimens among patients with extensive treatment histories and resistance profiles, especially when used in combination with other active agents. Other strategies include mega-highly active antiretroviral treatment, double-boosted protease inhibitors, structured treatment interruptions and maintaining a replicative compromised virus. The future development of newer agents with activity against resistant virus is desperately needed, and many new compounds and classes of antiretrovirals are currently being investigated.