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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
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 investigators choice, which can be either foscarnet 40 mg/kg every 8 hours or 60 mg/kg every 12 hours, or Cidofovir iv 5 mg/kg body weight given once weekly, or Cidofovir 1% or 3% topical applied 2 to 4 times daily, or Imiquimod 5% topical 3 times per week) (provided the drug is nationally approved).
Study 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 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 16 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2017-05-08
Primary completion: 2025-01-01
Study completion finish: 2025-04-01
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT03073967
Intervention or treatment
DRUG: Pritelivir
DRUG: Investigator's choice
Conditions
- • HSV Infection
Find a site
Closest Location:
Melbourne Health - Royal Melbourne Hospital
Research sites nearby
Select from list below to view details:
Melbourne Health - Royal Melbourne Hospital
Parkville, Not Specified, Australia
Westmead Hospital, Centre for Infectious Disease and Microbiology
Westmead, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part C, Pritelivir
| DRUG: Pritelivir
|
ACTIVE_COMPARATOR: Part C,
| DRUG: Investigator's choice
|
EXPERIMENTAL: Part D, Pritelivir
| DRUG: Pritelivir
|
EXPERIMENTAL: Part E, Pritelivir
| DRUG: Pritelivir
|
EXPERIMENTAL: Part F, Pritelivir
| DRUG: Pritelivir
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Efficacy measured by cure rate | Number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 28 days relative to the total number of subjects treated with trial medication in the respective treatment group. | Up to a maximum of 28 days |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Efficacy measured by cure rate | Number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 42 days relative to the total number of subjects treated with trial medication in the respective treatment group. | Up to a maximum of 42 days |
| Efficacy measured by time to lesion healing | Time to lesion healing, defined as complete epithelization of the mucocutaneous HSV lesion(s) within the treatment period and no appearance of new lesions, as assessed by the Investigator. | Up to a maximum of 42 days |
| Efficacy measured by recurrence rate | Recurrence rate at 2 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment. | At 2 months following post treatment visit, from randomization up to a maximum of 108 days |
| Efficacy measured by recurrence rate | Recurrence rate at 3 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment. | At 3 months following post treatment visit, from randomization up to a maximum of 139 days |
| Efficacy measured by pain rate | Number of days with pain at lesion site relative to the total number of days with analyzable pain data through daily subject self-reporting | Up to a maximum of 42 days |
| Efficacy measured by time to pain cessation at site of lesion | Starting at first dose of trial medication until pain is no longer reported by the subject (date and time) | Up to a maximum of 42 days |
| Efficacy measured by average pain score | Using a single-dimensional scale assessing pain intensity through daily subject self-reporting | Up to a maximum of 42 days |
| Efficacy measured by clinical shedding rate | Number of HSV positive swabs per subject relative to the total number of swabs collected per subject from lesion swabs taken from HSV lesion(s) | From date of randomization until the date of first documented healing, assessed up to a maximum of 42 days |
| Efficacy measured by time to cessation of shedding | Number of days until swabs taken are negative | Up to a maximum of 42 days |
| Efficacy measured by mean log number of HSV DNA copies | Mean log number of HSV DNA copies on HSV DNA positive swabs from lesion(s) as detected by quantitative real-time PCR (polymerase chain reaction). | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Efficacy measured by resistance to trial medication | Resistance to trial medication for lesions not healed within the treatment period or newly appeared lesions under treatment before or at the PoTV. | From date of randomization until the date of post treatment visit, assessed up to a maximum of 73 days |
| Safety measured by number of subjects developing chronic kidney disease | Chronic kidney disease | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing chronic kidney disease | Chronic kidney disease | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing acute Kidney Injury | Acute Kidney Injury (AKI) stage \>1 of KDIGO (Kidney Disease: Improving Global Outcome) criteria (increase in serum creatinine by 2.0 to 2.9 times compared to baseline or urine output \<0.5 mL/kg/h for \>12 hours) | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing renal impairment | Renal impairment | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing electrolyte abnormality | All abnormal values | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing seizures | All seizures | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by percentage of subjects developing anemia | Haemoglobin measurement | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by adverse events | Incidence of Adverse Events | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by haematology | Incidence of abnormal hematologic laboratory test results | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by lymphadenopathy | Incidence of lymphadenopathy measured by physical examination | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by CRP (C reactive protein ) | Incidence of CRP increase | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by cutaneous adverse events | Incidence of cutaneous adverse events by physical examination | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by (a)PTT (partial thromboplastin time) | Incidence of (a)PTT increase | From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days |
| Safety measured by discontinuation rate | Number of subjects discontinuing pritelivir or 'Inverstigator's Choice' due to AE(s) or intolerance relative to the total number of subjects treated with pritelivir or foscarnet, respectively | Up to a maximum of 42 days |
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