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

153 patients around the world

Available in Argentina, United States

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 Investigator's Choice. This trial part is designed to show superiority of pritelivir against Investigator's Choice in obtaining clinical cure, ie, number of subjects with all lesions healed within 28 days. - Part D is an open-label, multi-center 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 design to assess the safety and efficacy of pritelivir in subjects with acyclovir susceptible (ACV-S) mucocutaneous HSV episodes, (Part E is not being conducted in Germany). - Part F is an open-label, multi-center 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. Dosing of trial medication: Pritelivir oral tablet as single daily doses of 100 mg (following a loading dose of 400 mg as first dose) Comparator per investigator's choice (provided the drug listed below is nationally approved): Foscarnet intermittent infusions 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, or Cidofovir iv infusion of 5 mg/kg body weight given once weekly, or Cidofovir 1% or 3% topical treatment, applied 2 to 4 times daily, or Imiquimod 5% topical treatment, 3 times per week. Duration of treatment: 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 depending on the clinical progress.

AiCuris Anti-infective Cures AG

153Patients around the world

Requirements for the patient

From 16 Years

All Gender

Medical requirements

: 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.
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 with doses equivalent to or greater than the local agency approved high oral doses with of acyclovir, (800 mg TID) or valacyclovir or famciclovir.(1 g TID).
Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy or pharyngoscopy.
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.
Willingness to use highly effective birth control.
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.
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.
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).
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.
Recurrent mucocutaneous HSV infection considered ACV-S.

: Known resistance/intolerance to pritelivir and/or foscarnet or any of the excipients.
Previous treatment in PRIOH-1.
Need to use paclitaxel.
Baseline safety laboratory abnormalities.
History or current evidence of gastrointestinal malabsorption which, in the opinion of the Investigator, may affect the extent of absorption of pritelivir.
Severe renal insufficiency (eGFR ≤29 mL/min/1.73 m2).
History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other relevant diseases.
Abnormalities in hematological, clinical chemical or any other laboratory variables.
Not able to communicate meaningfully with the Investigator and site staff.
Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial.
Any other important local condition.
Pregnant and/or breastfeeding women.
Having received an investigational drug in an investigational drug trial unter certain conditions.
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.
known intolerance to pritelivir or any of the excipients and addition of 14. Having used (val)acyclovir within 3 days prior to starting pritelivir.

StudyPRIOH-1

SponsorAiCuris Anti-infective Cures AG

Study typeInterventional

Requirements

From 16 YearsAll Gender

Unique study IDclinicaltrials.gov

NCT03073967