Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects
- Registration Number
- NCT03073967
- Lead Sponsor
- AiCuris Anti-infective Cures AG
- Brief 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 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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 153
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C, Investigator's choice 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. Part C, Pritelivir Pritelivir Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days Part D, Pritelivir Pritelivir Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days Part E, Pritelivir Pritelivir Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days Part F, Pritelivir Pritelivir Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
- Primary Outcome Measures
Name Time Method Efficacy measured by cure rate Up to a maximum of 28 days 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.
- Secondary Outcome Measures
Name Time Method Efficacy measured by cure rate Up to a maximum of 42 days 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.
Efficacy measured by time to lesion healing Up to a maximum of 42 days 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.
Efficacy measured by recurrence rate At 3 months following post treatment visit, from randomization up to a maximum of 139 days 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.
Efficacy measured by pain rate Up to a maximum of 42 days Number of days with pain at lesion site relative to the total number of days with analyzable pain data through daily subject self-reporting
Efficacy measured by time to pain cessation at site of lesion Up to a maximum of 42 days Starting at first dose of trial medication until pain is no longer reported by the subject (date and time)
Efficacy measured by average pain score Up to a maximum of 42 days Using a single-dimensional scale assessing pain intensity through daily subject self-reporting
Efficacy measured by clinical shedding rate From date of randomization until the date of first documented healing, assessed up to a maximum of 42 days 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)
Efficacy measured by time to cessation of shedding Up to a maximum of 42 days Number of days until swabs taken are negative
Efficacy measured by mean log number of HSV DNA copies From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days 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).
Efficacy measured by resistance to trial medication From date of randomization until the date of post treatment visit, assessed up to a maximum of 73 days Resistance to trial medication for lesions not healed within the treatment period or newly appeared lesions under treatment before or at the PoTV.
Safety measured by number of subjects developing chronic kidney disease From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Chronic kidney disease
Safety measured by percentage of subjects developing chronic kidney disease From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Chronic kidney disease
Safety measured by percentage of subjects developing acute Kidney Injury From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days 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)
Safety measured by percentage of subjects developing renal impairment From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Renal impairment
Safety measured by percentage of subjects developing seizures From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days All seizures
Safety measured by percentage of subjects developing electrolyte abnormality From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days All abnormal values
Safety measured by percentage of subjects developing anemia From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Haemoglobin measurement
Safety measured by adverse events From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of Adverse Events
Safety measured by haematology From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of abnormal hematologic laboratory test results
Safety measured by lymphadenopathy From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of lymphadenopathy measured by physical examination
Safety measured by CRP (C reactive protein ) From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of CRP increase
Safety measured by cutaneous adverse events From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of cutaneous adverse events by physical examination
Safety measured by (a)PTT (partial thromboplastin time) From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days Incidence of (a)PTT increase
Safety measured by discontinuation rate Up to a maximum of 42 days 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
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (64)
Centre Hospitalier Universitaire Saint Pierre
🇧🇪Brussels, Belgium
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of South Alabama
🇺🇸Mobile, Alabama, United States
University Arizona - Department of Medicine Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
AZ Sint-Jan Brugge
🇧🇪Brugge, Belgium
University of California, Division of Infectious Diseases
🇺🇸Sacramento, California, United States
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
Midway Immunology and Research Center (MIRC)
🇺🇸Fort Pierce, Florida, United States
University of Florida (UF) - Division of Infectious Disease
🇺🇸Gainesville, Florida, United States
Links Clinical Trials
🇺🇸Miami, Florida, United States
Emory Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Department of Medicine J. H. Stroger Hospital of Cook County
🇺🇸Chicago, Illinois, United States
LSU Health Baton Rouge Pulmonary Clinic
🇺🇸Baton Rouge, Louisiana, United States
Tulane University - School of Medicine
🇺🇸New Orleans, Louisiana, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Rutgers Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Kings Country Hospital Center
🇺🇸Brooklyn, New York, United States
David H. Koch Center at Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Medical Center - Division of Infectious Diseases
🇺🇸Durham, North Carolina, United States
Atrium Health Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Hospital Rawson
🇦🇷Córdoba, Argentina
Sanatorio Mayo Privado S.A.
🇦🇷Córdoba, Argentina
Instituto FIDES
🇦🇷La Plata, Argentina
Melbourne Health - Royal Melbourne Hospital
🇦🇺Parkville, Australia
Westmead Hospital, Centre for Infectious Disease and Microbiology
🇦🇺Westmead, Australia
AZ Delta
🇧🇪Roeselare, Belgium
Alberta Health Services Cross Cancer Institute at the University of Alberta
🇨🇦Edmonton, Alberta, Canada
CHU Limoges - Centre national de reference des Herpes virus
🇫🇷Limoges, France
CHU de Nantes
🇫🇷Nantes, France
Hôpital Saint Louis - AP-HP
🇫🇷Paris, France
AP-HP Hopital Necker-Enfants Malades
🇫🇷Paris, France
AP-HP Hopital Bichat - Claude Bernard
🇫🇷Paris, France
LLC Diakor
🇬🇪Tbilisi, Georgia
Multiprofile Clinic Consilium Medulla LTD
🇬🇪Tbilisi, Georgia
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
General Hospital of Athens - Laiko
🇬🇷Athens, Greece
Regional University General Hospital of Heraklion
🇬🇷Heraklion, Greece
Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
Grande Ospedale Metropolitano "Bianchi Melacrino Morelli"
🇮🇹Calabria, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Unidad de Investigacion CIMA SC
🇲🇽Chihuahua, Mexico
Centro de Investigacion Clinica GRAMEL S.C.
🇲🇽Distrito Federal, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia A.C
🇲🇽Durango, Mexico
Centro de Investigacion Farmaceutica Especializado de Occidente S.C.
🇲🇽Guadalajara, Mexico
Arke SMO S.A. de C.V.
🇲🇽Veracruz, Mexico
Universitaetsspital Basel
🇨🇭Basel, Switzerland
Hopitaux universitaires de Geneve
🇨🇭Genève, Switzerland
Universitaetsspital Zuerich
🇨🇭Zuerich, Switzerland
Nhs Lothian
🇬🇧Edinburgh, United Kingdom
Research Department of Haematology, UCL Cancer Institute
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom