HB-502 + HB-501 for HIV

No longer recruiting at 5 trial locations

Overseen By General Hookipa Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hookipa Biotech GmbH

Must be taking: Antiretrovirals

Must not be taking: Systemic corticosteroids, Immunosuppressants

Disqualifiers: HIV malignancy, Neurocognitive disease, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, HB-502 and HB-501, for individuals with HIV who are already on antiretroviral therapy (ART). The goal is to determine if these treatments can enhance the immune system's ability to recognize and combat the virus. Participants will receive injections every eight weeks to assess the safety and effectiveness of this approach. It is suitable for those who have been on stable ART for at least 48 weeks and have very low HIV levels. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on stable antiretroviral treatment (ART) for at least 48 weeks before joining. It's best to discuss your specific medications with the trial team.

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

Research has shown that the HB-502 and HB-501 alternating 2-vector therapy is still under investigation for its safety in humans. The studies aim to assess how well people tolerate the treatment and identify any side effects. As a Phase 1 trial, the primary goal is to determine the treatment's safety for humans.

Previous patients have demonstrated that using two therapies like HB-502 and HB-501 can be effective and simpler than other treatments. However, the side effects or any negative reactions remain unclear. Phase 1 trials typically mark the first time the treatment is administered to humans, so safety data for large groups is not yet available.

Participants in this trial will receive injections every 8 weeks, and researchers will monitor them closely for any side effects. If the treatment proves safe in this phase, it will proceed to further testing to gather additional safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HB-502 and HB-501 because they represent a novel approach to HIV treatment through alternating 2-vector therapy. Unlike the current standard of care, which often involves daily antiretroviral pills, this treatment is administered via intramuscular injections just every eight weeks. The innovative 2-vector system could potentially enhance the immune response against HIV, offering a new mechanism of action that differs from conventional drugs. This advancement might lead to longer-lasting protection and a significant reduction in the frequency of dosing, which is a promising shift for managing HIV.

What evidence suggests that HB-502 and HB-501 alternating 2-vector therapy could be effective for HIV?

Research shows that HB-502 and HB-501 are designed to boost the body's immune response against HIV. In this trial, participants will receive either the HB-502 and HB-501 alternating 2-vector therapy at different dose levels or a placebo. These treatments help the body recognize and fight parts of the HIV virus. Hookipa's research indicates that these treatments can be administered multiple times without being hindered by existing antibodies, potentially strengthening the immune system. Early results from similar mRNA-based treatments have demonstrated their ability to produce antibodies against parts of the HIV virus, which may help control the infection. Although more breakthroughs are needed, these early results represent promising steps toward new ways to manage HIV. ^{1 5 6 7 8}

Who Is on the Research Team?

Head of Clinical Development

Principal Investigator

Hookipa Biotech GmbH

Are You a Good Fit for This Trial?

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

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.

Is in good general health according to the clinical judgment of the site Investigator

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HB-502 and HB-501 alternating 2-vector therapy or placebo by intramuscular injection every 8 weeks for 24 weeks

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the last dose of study treatment

24 weeks

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• HB-502 and HB-501 alternating 2-vector therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: HB-502 and HB-501 alternating 2-vector therapy (Dose Level 2) OR placebo Experimental Treatment 2 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 placebo Experimental Treatment 2 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).

Who Is Running the Clinical Trial?

Hookipa Biotech GmbH

Lead Sponsor

Trials

9

Recruited

1,100+

Published Research Related to This Trial

Inhibition of ATR using the drug AZD6738 significantly enhances the effectiveness of radiotherapy in both HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC) cell lines and xenograft models.

The radiosensitizing effect of AZD6738 is linked to the disruption of the G2/M cell cycle checkpoint, leading to reduced DNA repair and increased cell damage, suggesting a promising combination therapy for HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers. Dok, R., Glorieux, M., Bamps, M., et al.[2021]

Switching from a triple antiretroviral therapy (ART) regimen to a dual therapy of dolutegravir and lamivudine is effective and safe for people with HIV, showing non-inferiority in maintaining viral suppression over 48 weeks in a study of 265 participants.

The study found similar rates of adverse effects between the dual therapy and triple therapy groups, indicating that the simplified dual regimen does not compromise safety while providing effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Rojas, J., de Lazzari, E., Negredo, E., et al.[2021]

D-501036 is an effective anti-cancer drug that works by causing double strand DNA breaks in various human cancers, demonstrating strong anti-proliferative effects.

A resistant cell line (S4) showed increased ability to repair DNA damage through enhanced non-homologous end joining (NHEJ), suggesting that targeting NHEJ could help overcome resistance to D-501036 and similar DNA-damaging treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of non-homologous end joining DNA repair capacity confers cancer cells resistance to the novel selenophene compound, D-501036. Yang, YN., Chou, KM., Pan, WY., et al.[2021]

AZD0156 and AZD6738 are effective inhibitors of ATM and ATR, key proteins involved in DNA damage response, with pRAD50(Ser635) identified as a reliable biomarker for monitoring their pharmacodynamic effects in various cancers.

In preclinical models, AZD0156 significantly reduced pRAD50 levels in triple-negative breast cancer and colorectal cancer, indicating its potential efficacy, while pRAD50 levels can help assess ATM functionality in patients treated with ATR inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pRAD50: a novel and clinically applicable pharmacodynamic biomarker of both ATM and ATR inhibition identified using mass spectrometry and immunohistochemistry. Jones, GN., Rooney, C., Griffin, N., et al.[2021]

AZD6738 (ceralasertib) is a selective ATR kinase inhibitor that shows promise in treating cancer by modulating DNA damage response pathways, particularly in cells with defects in the ATM pathway or those experiencing replication stress.

In preclinical models, AZD6738 demonstrated significant antitumor activity, especially when combined with chemotherapy agents like carboplatin and irinotecan, achieving complete tumor regression in certain breast cancer models, suggesting its potential for clinical evaluation as both a monotherapy and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib. Wilson, Z., Odedra, R., Wallez, Y., et al.[2023]

Combination antiretroviral therapy (ART) has greatly reduced AIDS-related illnesses and deaths, but lifelong adherence to treatment is crucial for these benefits.

Emerging evidence suggests that two-drug regimens may be as effective as the traditional three-drug regimens for treating HIV-1, potentially offering a safer and more manageable treatment option for both new and experienced patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere? Kelly, SG., Nyaku, AN., Taiwo, BO.[2021]

Heavily treatment-experienced (HTE) individuals with HIV have limited options for antiretroviral therapy, often having only two or fewer ARV classes available, which complicates their treatment management.

A comprehensive understanding of past treatment failures, resistance diagnostics, and ARV pharmacology is essential for clinicians to effectively create personalized treatment regimens for HTE patients, utilizing both current and emerging ARVs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV: how to manage heavily treatment-experienced patients. Spivack, S., Pagkalinawan, S., Samuel, R., et al.[2022]

New antiretroviral agents like enfuvirtide and tipranavir/ritonavir have shown promising results in treating highly treatment-experienced HIV patients with drug resistance, especially when combined with other active medications.

There is a critical need for the development of new antiretroviral drugs that can effectively target resistant strains of HIV, as current treatment options are limited by factors like drug resistance and patient tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment strategies for highly treatment-experienced HIV-infected patients. Luber, AD.[2006]

A case series of 10 HIV-2-infected individuals in the U.S. showed that while highly active antiretroviral therapy (HAART) can be modified for HIV-2 treatment, it is generally less effective than for HIV-1.

The study found a strong correlation between CD4+ cell count, HIV-2 virus load, and clinical status, suggesting that monitoring HIV-2 virus load is important for managing treatment, but more controlled clinical trials are needed to optimize therapy for HIV-2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly active antiretroviral therapy and viral response in HIV type 2 infection. Mullins, C., Eisen, G., Popper, S., et al.[2006]

In a study of 84 HIV-infected patients, the combination of boosted darunavir and rilpivirine was effective, with 87.7% achieving viral loads below 50 copies/mL after 48 weeks, demonstrating its efficacy in a cohort with a history of multiple treatments.

The regimen was well-tolerated and showed good effectiveness even in patients with prior resistance to other HIV medications, indicating its potential as a simplified treatment option for those with long-term HIV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of boosted darunavir plus rilpivirine in patients with long-lasting HIV-1 infection: DARIL study. Navarro, J., González-Cordón, A., Casado, JL., et al.[2022]

In a study of five patients dually infected with HIV-1 and HIV-2, four patients showed undetectable viral loads for HIV-1 while receiving efavirenz-based therapy, but only limited increases in CD4+ counts.

One patient treated with a protease inhibitor regimen achieved undetectable viral loads for both HIV-1 and HIV-2, suggesting that protease inhibitors may be more effective for this type of dual infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virologic and immunologic responses to antiretroviral therapy among HIV-1 and HIV-2 dually infected patients: case reports from Abidjan, Côte d'Ivoire. Borget, MY., Diallo, K., Adje-Toure, C., et al.[2009]

In a study of 20 highly antiretroviral treatment-experienced HIV-infected patients, dual therapy with atazanavir (ATV) and raltegravir (RAL) successfully maintained viral suppression below 400 HIV RNA copies/ml over 18 months, with only one participant showing a detectable viral load.

While the therapy was generally effective, five participants switched regimens due to adverse events, including fatigue and gastrointestinal issues, suggesting that while the dual therapy is promising, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir and unboosted atazanavir dual therapy in virologically suppressed antiretroviral treatment-experienced HIV patients. Cordery, DV., Hesse, K., Amin, J., et al.[2015]

The phase I study of M3541, an ATM kinase inhibitor, showed that it was well tolerated at doses up to 300 mg during palliative radiotherapy, with only one patient experiencing dose-limiting toxicities that were manageable with antibiotics.

Despite some patients showing a partial or complete response to treatment, the study was halted early due to the lack of a clear dose-response relationship and suboptimal pharmacokinetics, leading to no further clinical development of M3541.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors. Waqar, SN., Robinson, C., Olszanski, AJ., et al.[2022]

Dual antiretroviral therapies, particularly the combination of dolutegravir plus rilpivirine, have been found to be safe and effective for maintaining viral suppression in HIV patients, offering a simpler alternative to traditional triple therapy.

Switching to dual therapy can potentially reduce long-term side effects, lower costs, and improve drug adherence, marking a significant shift in HIV treatment strategies towards induction-maintenance approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual antiretroviral therapy for HIV infection. Soriano, V., Fernandez-Montero, JV., Benitez-Gutierrez, L., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06430905

Study Details | NCT06430905 | Safety, Reactogenicity and ... The study will evaluate the safety, reactogenicity, and immunogenicity of HB-502 and HB-501 alternating 2-vector therapy. HB-502 and HB-501 are genetically ...

2. withpower.com withpower.com/clinical-trials/for-hiv-aids?page=3

Top HIV/AIDS Clinical Trials | Power 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11391700/

mRNA-based HIV-1 vaccines - PMC - PubMed Central - NIH The protection from HIV-1 acquisition was associated with tier 1 (non/weakly neutralizing) antibodies against the V2 loop of the gp120 subunit of HIV-1 envelope ...

4. treatmentactiongroup.org treatmentactiongroup.org/wp-content/uploads/2024/07/pipeline_HIV_cure_and_ibt_2024_final.pdf

Pipeline Report » 2024 Research toward a widely applicable cure for HIV continues to make incremental progress, but no major breakthroughs have been reported over ...

5. synapse.patsnap.com synapse.patsnap.com/organization/e062f2a3bd77325108ddf69367898508

HOOKIPA Pharma, Inc. - Drug pipelines, Patents, Clinical ... Hookipa's vectors are not hindered by vector-neutralizing antibodies and can be administered multiple times, providing enhanced immune protection. The levels of ...

6. withpower.com withpower.com/trial/phase-1-acquired-immunodeficiency-syndrome-5-2024-b8513

HB-502 + HB-501 for HIV · Info for Participants 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 ...

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-safety-reactogenicity-immunogenicity-hb-502-501-versus-placebo-trial-nct06430905

Safety, Reactogenicity and Immunogenicity of HB-502 and ... A Study Evaluating the Safety and Effectiveness of an Experimental Treatment for HIV ... Participants will receive either the experimental treatment (HB-502 and ...

8. reporter.nih.gov reporter.nih.gov/search/0FOpySKAWEm6pYfhuqe3aw/project-details/11250947

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