Summary

Eligibility
for people ages 16 years and up (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
estimated completion

Description

Summary

Randomized, open-label, multi-center, comparative trial to assess the efficacy and safety in immunocompromised subjects with acyclovir resistant or acyclovir susceptible mucocutaneous HSV infection, treated with pritelivir 100 mg once daily (following a loading dose of 400 mg as first dose to rapidly reach steady-state plasma concentration) or foscarnet 40 mg/kg every 8 hours or 60 mg/kg every 12 hours.

Official Title

A Randomized, Open Label, Multi-center, Comparative Trial, to Assess the Efficacy and Safety of Pritelivir Versus Foscarnet for the Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (PRIOH-1)

Details

The trial comprises 5 Parts, Part A, B, C, D, E and F. Part A and Part B (Phase 2) have been finalised. - Part A is a randomized, open-label, multi-center, comparative design to assess the efficacy and safety in subjects with ACV-resistant mucocutaneous HSV infection, treated with oral pritelivir or intravenous foscarnet. - Part B is an open-label, multi-center design to assess the efficacy and safety of pritelivir in subjects with ACV-resistant-mucocutaneous HSV and who either: 1. present with foscarnet-resistance/intolerance, or 2. developed foscarnet resistance/intolerance during treatment in Part A (no improvement after at least 5 days of foscarnet therapy or intolerance to foscarnet requiring cessation of foscarnet treatment). Parts C, D, E and F (Phase 3). - Part C is a randomized, open-label, multi-center, comparative design to assess the efficacy and safety of oral pritelivir in subjects with acyclovir resistent (ACV-R) mucocutaneous HSV episodes. Subjects with ACV-R mucocutaneous HSV infection will be randomized 1:1 to receive either oral pritelivir or iv foscarnet. The trial is designed to show superiority of pritelivir against foscarnet in obtaining clinical cure, ie, number of subjects with all lesions healed within 28 days. - Part D is an open-label, multi-center (performed in the same trial sites as Part C) design to assess the efficacy and safety of pritelivir in subjects with ACV-R mucocutaneous HSV episodes and who in addition either: 1. present with iv foscarnet resistance/intolerance already at Screening for inclusion, or 2. developed foscarnet resistance/intolerance during treatment in Part C (no improvement after at least 7 days of foscarnet treatment or intolerance to foscarnet requiring cessation of foscarnet treatment). Part D has been closed in June 2022. - Part E is an open-label, multi-center (performed in the same trial sites as Part C) design to assess the safety and efficacy of pritelivir in subjects with acyclovir susceptible (ACV-S) mucocutaneous HSV episodes, (Part E is not beeing conducted in Germany). - Part F is an open-label, multi-center (performed in the same trial sites as Part C) design to assess the efficacy and safety of pritelivir in subjects with ACV-R mucocutaneous HSV episodes and who in addition either: 1. present with iv foscarnet resistance/intolerance already at Screening for inclusion, or 2. developed foscarnet resistance/intolerance during treatment in Part C (no improvement after at least 7 days of foscarnet treatment or intolerance to foscarnet requiring cessation of foscarnet treatment). 3. cannot be enrolled into Part D anymore because enrollment into Part D has been completed. Pritelivir trial medication will be given orally as single daily doses of 100 mg (following a loading dose of 400 mg as first dose) until all mucocutaneous HSV lesions are healed or up to 28 days, whichever is earlier. A prolongation up to a maximum of 42 days may be possible. Foscarnet will be given as intermittent infusions at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours (to be adjusted in case of renal impairment) for a minimum of 1 hour duration until all mucocutaneous HSV lesions are healed or up to 28 days, whichever is earlier. A prolongation up to a maximum of 42 days may be possible.

Keywords

HSV Infection Infections Communicable Diseases Herpes Simplex Foscarnet Pritelivir

Eligibility

For people ages 16 years and up

Part C inclusion criteria

  1. Immunocompromised men and women of any ethnic group aged ≥16 years.

In Canada, Germany, Belgium:

Immunocompromised (due to conditions including HIV infection, hematopoietic cell or solid organ transplantation, and chronic glucocorticoid use) men and women of any ethnic group aged >18 years.

  1. ACV-R mucocutaneous HSV infection based on clinical failure, requiring switch to foscarnet treatment or positive genotypic/phenotypic ACV resistance testing for current lesion. Clinical failure is defined as no improvement after oral or iv doses for at least 7 days withat doses equivalent to or greater than the local agency approved high oral doses withof acyclovir, (800 mg TID) or valacyclovir or famciclovir.(1 g TID).
  2. Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy or pharyngoscopy.
  3. Willingness to abstain from the application of lotions and/or creams to the area with HSV lesions. Wet/dry saline dressings or bandages at lesion site are allowed.
  4. Willingness to use highly effective birth control.
  5. Subject, and/or their legally authorized representative, (proxy consent is not permitted in Germany), must be willing and able to understand the Informed Consent Form.
  6. Negative serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential at Screening and a negative urine pregnancy test at Day 1.
  7. Written informed consent. For subjects, who are unable to provide informed consent for whatever reason, written consent must be obtained from the legal representative, (proxy consent is not permitted in Germany).

Part D and F inclusion criteria

All inclusion criteria as for Part C, except for inclusion criterion 2, which is replaced by:

  1. ACV-R and foscarnet-R mucocutaneous HSV infection based on clinical failure or positive genotypic/phenotypic resistance testing for current lesion or documented intolerance to iv foscarnet requiring cessation of foscarnet treatment or precluding foscarnet treatment.

Subjects will be able to enter Part F only after closure of enrollment in Part D.

Part E inclusion (Part E is not being conducted in Germany)

All inclusion criteria as for Part C, except for inclusion criterion 2, which is replaced by:

  1. Recurrent mucocutaneous HSV infection considered ACV-S.

Part C exclusion criteria

  1. Known resistance/intolerance to pritelivir and/or foscarnet or any of the excipients.
  2. Previous treatment in PRIOH-1.
  3. Need to use paclitaxel.
  4. Baseline safety laboratory abnormalities.
  5. History or current evidence of gastrointestinal malabsorption which, in the opinion of the Investigator, may affect the extent of absorption of pritelivir.
  6. Severe renal insufficiency (eGFR ≤29 mL/min/1.73 m2).
  7. History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other relevant diseases.
  8. Abnormalities in hematological, clinical chemical or any other laboratory variables.
  9. Not able to communicate meaningfully with the Investigator and site staff.
  10. . Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial.
  11. . Any other important local condition.
  12. . Pregnant and/or breastfeeding women.
  13. . Having received an investigational drug in an investigational drug trial unter certain conditions.

Part D exclusion criteria

All exclusion criteria as for Part C, except for exclusion criterion 1, which is replaced by: 1. Known intolerance to pritelivir or any of the excipients and except criterion 13, which is replaced by: 13. Having received an investigational drug in an investigational drug within 7 half-lives after the last administration of this drug before initiating trial medication, except for subjects entering Part D, who have previously received foscarnet treatment in Part C of this trial.

Participation in a clinical trial without receiving other investigational drugs (eg, follow-up phase of a trial, observational study) is permitted.

Part E exclusion criteria (Part E is not being conducted in Germany)

All exclusion criteria as for Part C, except for exclusion criteria 1, which is replaced by

  1. known intolerance to pritelivir or any of the excipients and addition of 14. Having used (val)acyclovir within 3 days prior to starting pritelivir.

Part F exclusion criteria All exclusion criteria for Part D plus 14. Part D open for enrollment

Locations

  • University of California, Division of Infectious Diseases accepting new patients
    Sacramento California 95817 United States
  • Cedars-Sinai Medical Center accepting new patients
    Los Angeles California 90048 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AiCuris Anti-infective Cures AG
Links
Sign up for this study
ID
NCT03073967
Phase
Phase 3 HSV Infection Research Study
Study Type
Interventional
Participants
Expecting 153 study participants
Last Updated