HB-502 + HB-501 for HIV

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

30 Participants Needed

Trial Summary

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.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the HB-502 and HB-501 alternating 2-vector therapy for HIV?

There is increasing evidence that two-drug regimens can be effective alternatives to the traditional three-drug regimens for HIV treatment, as they may offer similar benefits with potentially fewer side effects. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

Is 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. ^{4 11 12 13 14}

How is the HB-502 and HB-501 alternating 2-vector therapy different from other HIV treatments?

The HB-502 and HB-501 alternating 2-vector therapy is unique because it uses a two-drug regimen instead of the traditional three-drug combination, potentially reducing long-term side effects and improving adherence. This approach aligns with recent trends in HIV treatment that focus on simpler, dual therapies to manage the condition effectively. ^{4 11 12 13 14}

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.

Research Team

Head of Clinical Development

Principal Investigator

Hookipa Biotech GmbH

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Highly active antiretroviral therapy and viral response in HIV type 2 infection. [2006]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of boosted darunavir plus rilpivirine in patients with long-lasting HIV-1 infection: DARIL study. [2022]

3. Netherlands 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. [2009]

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

Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere? [2021]

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

Raltegravir and unboosted atazanavir dual therapy in virologically suppressed antiretroviral treatment-experienced HIV patients. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers. [2021]

7. Ireland 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. [2021]

8. England 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. [2021]

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

Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors. [2022]

10. United States 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Dual antiretroviral therapy for HIV infection. [2017]

12. England pubmed.ncbi.nlm.nih.gov

HIV: how to manage heavily treatment-experienced patients. [2022]

13. Netherlands 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. [2021]

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

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