Pritelivir vs Foscarnet for Resistant Herpes

(PRIOH-1 Trial)

Not currently recruiting at 90 trial locations

Overseen By Medpace

Age: Any Age

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: AiCuris Anti-infective Cures GmbH

Must not be taking: Acyclovir, Valacyclovir, Famciclovir

Disqualifiers: Pregnancy, Hemodialysis, Significant diseases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, pritelivir and foscarnet, for individuals with difficult-to-treat herpes due to a weakened immune system. The researchers aim to determine which treatment is safer and more effective for those whose herpes does not respond to standard medications like acyclovir. Participants may receive either daily pritelivir or a doctor-selected treatment such as foscarnet (also known as Foscavir) or another approved medication. Individuals with a history of herpes unresponsive to standard treatment and who can assess their lesions may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are joining Part E, you must not have used acyclovir, valacyclovir, or famciclovir within 3 days before starting pritelivir.

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

Research has shown that pritelivir demonstrates promising safety results in studies involving healthy individuals with genital HSV-2 infections. These studies suggest that pritelivir is generally well-tolerated, with mostly mild side effects like headaches or nausea.

For foscarnet, already approved by the FDA for certain infections, safety information is well-established. However, it can cause serious side effects, such as kidney problems and changes in blood minerals, requiring patient monitoring to manage these risks.

Both treatments aim to assist those with resistant herpes infections. Discussing potential side effects with a healthcare provider is important before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pritelivir because it offers a novel approach to treating resistant herpes. Unlike standard treatments like Foscarnet, which are administered intravenously and can be cumbersome, Pritelivir is taken orally as a tablet. This oral administration is more convenient and could potentially improve patient compliance. Moreover, Pritelivir works by inhibiting the helicase-primase complex of the virus, a different mechanism than the DNA polymerase inhibition seen in current treatments, which might offer effectiveness against resistant strains. This unique mechanism and easier delivery method make Pritelivir a promising new option for those struggling with difficult-to-treat herpes.

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

This trial will compare Pritelivir and Foscarnet for treating resistant herpes infections. Studies have shown that Pritelivir effectively treats herpes infections unresponsive to acyclovir, particularly in individuals with weakened immune systems. Research indicates that Pritelivir blocks a protein essential for the herpes virus's growth, reducing the infection. Initial findings suggest that Pritelivir remains effective over time, with no signs of the herpes virus developing resistance. Meanwhile, Foscarnet, another treatment option in this trial, is already known to combat resistant herpes strains and is commonly used when other treatments fail. Both treatments offer hope for managing herpes infections that don't respond to usual medications. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for immunocompromised adults over 18 years old with mucocutaneous HSV infections resistant to acyclovir. Participants must be willing to use effective birth control and have lesions that can be visually inspected. Pregnant women, individuals unable to consent, or those not following specific treatment protocols are excluded.

Inclusion Criteria

You must be able to understand the information provided in the Informed Consent Form, and agree to participate in the study.

I am 16 or older and have a weakened immune system.

I have given or my legal representative has given written consent for me to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pritelivir or Investigator's Choice for up to 28 days, with potential prolongation up to 42 days

4-6 weeks

Weekly visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 weeks

Monthly visits (in-person or virtual)

Long-term follow-up

Participants are assessed for recurrence and long-term safety outcomes

3 months

Telephone follow-up at 3 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Foscarnet
• Pritelivir

Trial Overview The study compares the effectiveness of Pritelivir tablets (with an initial high dose) against Foscarnet injections in treating herpes infections in people with weakened immune systems. It's a randomized and open-label trial, meaning both researchers and participants know which treatment is given.

How Is the Trial Designed?

Group I: Part F, Pritelivir Experimental Treatment 1 Intervention

Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days

Group II: Part E, Pritelivir Experimental Treatment 1 Intervention

Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days

Group III: Part D, Pritelivir Experimental Treatment 1 Intervention

Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days

Group IV: Part C, Pritelivir Experimental Treatment 1 Intervention

Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days

Group V: Part C, Active Control 1 Intervention

Investigator's Choice: Foscarnet iv, 40 mg/kg tid or 60mg/kg bid or Cidofovir iv, 5 mg/kg body weight given once weekly or Cidofovir 1% or 3%, topically applied 2 to 4 times daily or Imiquimod 5%, topically applied 3 times per week, for up to 28 days and potential prolongation for up to additional 14 days.

Foscarnet is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Foscavir for:

• Herpes simplex virus infections
• Cytomegalovirus retinitis

Approved in United States as Foscavir for:

• Herpes simplex virus infections
• Cytomegalovirus retinitis

Approved in Canada as Foscavir for:

• Herpes simplex virus infections
• Cytomegalovirus retinitis

Approved in Japan as Foscavir for:

• Herpes simplex virus infections
• Cytomegalovirus retinitis

Who Is Running the Clinical Trial?

AiCuris Anti-infective Cures GmbH

Lead Sponsor

Trials

5

Recruited

900+

AiCuris Anti-infective Cures AG

Lead Sponsor

Trials

9

Recruited

2,000+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

In a study of 14 AIDS patients with acyclovir-resistant herpes simplex lesions, foscarnet was found to be highly effective, with all patients experiencing complete healing within 10 to 24 days, while vidarabine failed in all cases.

Foscarnet demonstrated significantly shorter healing times and less toxicity compared to vidarabine, making it a better option for treating acyclovir-resistant infections, although patients experienced a high rate of relapse after treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. Safrin, S., Crumpacker, C., Chatis, P., et al.[2013]

Foscarnet, an antiviral medication used to treat herpes viruses, has been associated with severe penile ulcers in some patients, highlighting a potential safety concern.

This case report emphasizes the need for monitoring and awareness of possible adverse effects, such as ulceration, when initiating intravenous foscarnet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foscarnet-induced penile ulceration. Torres, T., Fernandes, I., Sanches, M., et al.[2014]

In a study of six HIV-infected patients with herpes simplex virus type 2 lesions resistant to foscarnet, five had previously used foscarnet for managing acyclovir-resistant infections, indicating that foscarnet resistance can develop in immunosuppressed individuals.

Switching to or adding acyclovir to foscarnet therapy led to healing in three patients, suggesting that acyclovir may be an effective alternative treatment for those suspected of having foscarnet-resistant HSV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foscarnet-resistant herpes simplex virus infection in patients with AIDS. Safrin, S., Kemmerly, S., Plotkin, B., et al.[2019]

A 73-year-old woman with B-cell lymphatic leukemia and acyclovir-resistant herpes simplex infection was successfully treated with intravenous foscarnet, leading to nearly complete remission of her perianal ulcers after 3 months.

This case highlights the potential effectiveness of foscarnet as an alternative treatment for acyclovir-resistant herpes simplex infections in immunocompromised patients, while also considering the safety and side effects of different antiviral options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acyclovir-resistant herpes exulcerans et persistens. Type II]. Klammer, M., Kuhn, A., Ruzicka, T., et al.[2018]

Among 196 allogeneic stem cell transplant recipients, 14 cases of severe acyclovir-resistant HSV-1 infections were identified, highlighting a significant concern for this patient population, especially those receiving unrelated transplants.

While foscarnet was administered to all patients, and cidofovir was given to some, the effectiveness of these treatments was limited, with only 5 out of 7 patients showing a complete response, indicating a need for reassessment of current treatment strategies for resistant HSV-1 infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation. Chen, Y., Scieux, C., Garrait, V., et al.[2018]

In a study of 26 HIV-infected patients with acyclovir-resistant herpes simplex virus (HSV), foscarnet therapy showed a clinical response in 81% of patients, with 73% achieving complete healing of lesions.

Foscarnet was effective in stopping viral shedding in all 11 patients who were retested, and while adverse effects were common, only 12% of patients had to stop treatment due to toxicity, compared to 29% for those treated with the alternative drug vidarabine, which was ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. Safrin, S., Assaykeen, T., Follansbee, S., et al.[2019]

A study of 27 foscarnet-resistant herpes simplex virus type 1 (HSV-1) isolates revealed specific mutations in the viral DNA polymerase that confer resistance, particularly an amino acid substitution at position 724.

Despite resistance to foscarnet, most of the HSV-1 isolates remained sensitive or hypersensitive to alternative antiviral medications like cidofovir and ganciclovir, suggesting these could be effective treatment options for infections caused by foscarnet-resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotypic characterization of the DNA polymerase and sensitivity to antiviral compounds of foscarnet-resistant herpes simplex virus type 1 (HSV-1) derived from a foscarnet-sensitive HSV-1 strain. Saijo, M., Suzutani, T., Morikawa, S., et al.[2019]

In an AIDS patient with a severe and persistent herpes simplex virus (HSV) type II infection, high-dose acyclovir treatment was ineffective, suggesting the presence of an acyclovir-resistant strain of the virus.

Intravenous Foscarnet treatment led to almost complete clearing of the lesions within 3 weeks, with no relapse observed over a 4-month follow-up, indicating its potential as an effective alternative for acyclovir-resistant HSV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic erosive, therapy-resistant perianal herpes (type II) with herpes proctitis in AIDS]. Bratzke, B., Orfanos, CE., Stavermann, T., et al.[2013]

Foscarnet has been shown to be effective in treating acyclovir-resistant herpes simplex virus (HSV) infections in HIV-infected patients, significantly reducing healing time, viral shedding, and pain, as demonstrated in a clinical trial.

The study highlighted that while initial herpetic lesions were mostly susceptible to acyclovir, all patients eventually experienced recurrences due to acyclovir-resistant HSV, indicating a need for further research on optimal management strategies for recurrent infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acyclovir-resistant herpes simplex virus infections in patients with AIDS. Safrin, S.[2020]

A case study of an immunosuppressed patient with aciclovir-resistant HSV-2 showed that the novel oral helicase-primase inhibitor pritelivir effectively controlled both symptoms and the virus itself, demonstrating its potential as a treatment option.

This case represents the first clinical use of pritelivir in the UK, highlighting its promise as an alternative therapy for patients who do not respond to traditional antiviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2. Cannon, L., Tholouli, E., Ward, C., et al.[2022]

Citations

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Discovery, Chemistry, and Preclinical Development of ... Herpesviruses have been constant companions of many animal species for millions of years. Of the two subtypes of herpes simplex viruses (HSV), ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03073967

NCT03073967 | Trial on Efficacy and Safety of Pritelivir ... Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant ... HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects ( ...

3. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2020-004940-27/FR

Clinical Trials Register A clinical trial to assess the efficacy and safety of pritelivir ... Acyclovir-resistant mucocutaneous HSV infections in immunocompromised ...

4. academic.oup.com academic.oup.com/jid/article/214/2/258/2572113

No Evidence of Pritelivir Resistance Among Herpes Simplex ... This study demonstrates evidence of retained susceptibility of HSV-2 to pritelivir in immunocompetent persons following daily therapy for up to 28 days. herpes ...

5. journals.asm.org journals.asm.org/doi/10.1128/aac.01732-22

Salvage Treatment of Refractory HSV Oral Lesions with ... Allogeneic hematopoietic cell transplantation (HCT) recipients (r) may develop acyclovir-resistant or refractory herpes simplex virus (r/r HSV) ...

6. medchemexpress.com medchemexpress.com/BAY-57-1293.html?srsltid=AfmBOorNu0-4wfhcKKGrtaOGvCwHe2XWvUWBh1bp4f6ViF5ML_EWn9_i

Pritelivir (AIC316) | HSV Inhibitor Pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1301150

Helicase–Primase Inhibitor Pritelivir for HSV-2 Infection ... safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. ... herpes simplex virus primase-helicase inhibitor BAY 57-1293.

8. invivochem.com invivochem.com/pritelivir-bay-57-1293.html

Pritelivir; 348086-71-5; BAY 57-1293 BAY 57-1293 also shows potent antiviral activity against acyclovir resistant HSV mutants. BAY 57-1293 reduces Aβ and P-tau induced by herpes simplex virus ...

9. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.2c00668

Discovery, Chemistry, and Preclinical Development of Pritelivir ... As acyclovir and its congeners are notably safe drugs, any new medicine in the field of HSV infections should reach or exceed this safety bar, ...

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Pritelivir - an overview Herpes Simplex Virus and Varicella-zoster Virus. The major antiviral agents used for prophylaxis (and treatment) of HSV and VZV are acyclovir, its valyl-ester ...