Pritelivir vs Foscarnet for Resistant Herpes

(PRIOH-1 Trial)

Recruiting at69 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AiCuris Anti-infective Cures GmbH

Must not be taking: Acyclovir, Valacyclovir, Famciclovir

Disqualifiers: Pregnancy, Hemodialysis, Significant diseases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares two treatments for herpes infections in patients with weakened immune systems who do not respond to standard treatment. One treatment is a pill called pritelivir, and the other is a drug called foscarnet. Both aim to stop the virus from replicating and help heal sores. Foscarnet has been used to treat herpes viruses, including drug-resistant cytomegalovirus (CMV) and herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2).

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.

What data supports the idea that Pritelivir vs Foscarnet for Resistant Herpes is an effective drug?

The available research shows that Foscarnet is effective for treating acyclovir-resistant herpes in patients with AIDS. In one study, 81% of patients showed a clinical response, and 73% had complete healing of their lesions. Another study found that Foscarnet led to significant improvements in healing time and pain reduction compared to another drug, vidarabine. However, some patients developed resistance to Foscarnet, suggesting that while it is effective for many, it may not work for everyone. There is no specific data on Pritelivir in the provided information, so its effectiveness compared to Foscarnet cannot be determined from this data. ^{1 2 3 4 5}

What safety data exists for Pritelivir and Foscarnet in treating resistant herpes?

Foscarnet has been used to treat acyclovir-resistant herpes simplex virus (HSV) infections, particularly in immunocompromised patients such as those with AIDS. Clinical response rates are high, but adverse effects are common, with 12% of patients needing to discontinue due to toxicity. Foscarnet can cause severe side effects, including penile ulceration. Pritelivir, also known as AIC-316 or BAY 57-1293, is not mentioned in the provided research, so specific safety data for Pritelivir in this context is not available from these sources. ^{2 4 6 7 8}

Is the drug Foscarnet a promising treatment for resistant herpes?

Yes, Foscarnet is a promising treatment for resistant herpes. It has been shown to effectively heal lesions, stop the virus from spreading, and reduce pain in patients with acyclovir-resistant herpes infections. ^{1 3 7 9 10}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Foscarnet (Antiviral)
• Pritelivir (Virus Therapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

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

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

Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. [2019]

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

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation. [2018]

4. United States 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. [2013]

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

Foscarnet-resistant herpes simplex virus infection in patients with AIDS. [2019]

6. Slovenia pubmed.ncbi.nlm.nih.gov

Foscarnet-induced penile ulceration. [2014]

7. United States 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. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Acyclovir-resistant herpes exulcerans et persistens. Type II]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[Chronic erosive, therapy-resistant perianal herpes (type II) with herpes proctitis in AIDS]. [2013]