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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 (PRIOH-1)

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ClinicalTrials.gov Identifier: NCT03073967
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : October 11, 2021
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
AiCuris Anti-infective Cures GmbH

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 foscarnet 40 mg/kg every 8 hours or 60 mg/kg every 12 hours.

Condition or disease Intervention/treatment Phase
HSV Infection Drug: Pritelivir Drug: Foscarnet Phase 3

Detailed Description:

The trial comprises 5 Parts, Part A, B, C, D and E. Part A and Part B (Phase 2) have been closed in November 2020.

  • 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 and E (Phase 3) are currently being set-up.

  • 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, i.e. 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 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 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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Herpes Simplex

Arm Intervention/treatment
Experimental: Part C, 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
Drug: Pritelivir
100 mg tablets

Active Comparator: Part C, Foscarnet
iv solution, 40 mg/kg tid or 60mg/kg bid for up to 28 days and potential prolongation for up to additional 14 days.
Drug: Foscarnet
Solution for iv infusion

Experimental: Part D, 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
Drug: Pritelivir
100 mg tablets

Experimental: Part E, 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
Drug: Pritelivir
100 mg tablets




Primary Outcome Measures :
  1. Efficacy measured by cure rate [ Time Frame: 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 :
  1. Efficacy measured by cure rate [ Time Frame: 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.

  2. Efficacy measured by time to lesion healing [ Time Frame: 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.

  3. Efficacy measured by recurrence rate [ Time Frame: At 2 months following post treatment visit, from randomization up to a maximum of 108 days ]
    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.

  4. Efficacy measured by recurrence rate [ Time Frame: 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.

  5. Efficacy measured by pain rate [ Time Frame: 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

  6. Efficacy measured by time to pain cessation at site of lesion [ Time Frame: 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)

  7. Efficacy measured by average pain score [ Time Frame: Up to a maximum of 42 days ]
    Using a single-dimensional scale assessing pain intensity through daily subject self-reporting

  8. Efficacy measured by clinical shedding rate [ Time Frame: 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)

  9. Efficacy measured by time to cessation of shedding [ Time Frame: Up to a maximum of 42 days ]
    Number of days until swabs taken are negative

  10. Efficacy measured by mean log number of HSV DNA copies [ Time Frame: 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).

  11. Efficacy measured by resistance to trial medication [ Time Frame: 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.

  12. Safety measured by number of subjects developing chronic kidney disease [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Chronic kidney disease

  13. Safety measured by percentage of subjects developing chronic kidney disease [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Chronic kidney disease

  14. Safety measured by number of subjects developing acute Kidney Injury [ Time Frame: 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)

  15. Safety measured by number of subjects developing renal impairment [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Renal impairment

  16. Safety measured by percentage of subjects developing renal impairment [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Renal impairment

  17. Safety measured by number of subjects developing electrolyte abnormality [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    All abnormal values

  18. Safety measured by number of subjects developing seizures [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    All seizures

  19. Safety measured by number of subjects developing anemia [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Haemoglobin measurement

  20. Safety measured by adverse events [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Incidence of Adverse Events

  21. Safety measured by haematology [ Time Frame: 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

  22. Safety measured by lymphadenopathy [ Time Frame: 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

  23. Safety measured by CRP (C reactive protein ) [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]
    Incidence of CRP increase

  24. Safety measured by cutaneous adverse events [ Time Frame: 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

  25. Safety measured by (a)PTT (partial thromboplastin time) [ Time Frame: 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

  26. Safety measured by discontinuation rate [ Time Frame: Up to a maximum of 42 days ]
    Number of subjects discontinuing pritelivir or foscarnet due to AE(s) or intolerance relative to the total number of subjects treated with pritelivir or foscarnet, respectively



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Part C inclusion criteria

  1. Immunocompromised men and women of any ethnic group aged ≥16 years.
  2. ACV-R mucocutaneous HSV infection based on clinical failure requiring switch to foscarnet treatment or positive ACV resistance testing for current lesion.
  3. Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy or pharyngoscopy.
  4. 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.
  5. Willingness to use highly effective birth control.
  6. Subject, and/or their legally authorized representative, must be willing and able to understand the Informed Consent Form.
  7. 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.
  8. Written informed consent. For subjects, who are unable to provide informed consent for whatever reason, written consent must be obtained from the legal representative.

Part D inclusion criteria

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

2. 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 foscarnet requiring cessation of foscarnet treatment or precluding foscarnet treatment.

Part E inclusion criteria

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

2. 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 warfarin, phenytoin, 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).
  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

All exclusion criteria as for Part C, except for exclusion criteria 1, which is replaced by known intolerance to pritelivir or any of the excipients and 14. Having used (val)acyclovir within 3 days prior to starting pritelivir.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03073967


Locations
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United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Grace Funke       grace.funke@cshs.org   
United States, Connecticut
Yale University School of Medicine - Infectious Diseases Recruiting
New Haven, Connecticut, United States, 06510
Contact: Rodolfo N. Molina, M.D.    203-785-7031    Rodolfo.molina@yale.edu   
United States, Florida
Midland Florida Clinical Research Center, LLC Recruiting
DeLand, Florida, United States, 32720
Contact: Jack Dienes    386-279-6181    jackdienes.mfcrc@gmail.com   
Midway Immunology and Research Center (MIRC) Recruiting
Fort Pierce, Florida, United States, 34982
Contact: Carly Sharp    772-595-9830    info@midwayresearch.com   
United States, Georgia
Emory Hospital Midtown Infectious Disease Clinic Recruiting
Atlanta, Georgia, United States, 30308
Contact: Joan Lopez    404-686-5198    jllopez@emory.edu   
United States, Illinois
Department of Medicine J. H. Stroger Hospital of Cook County Recruiting
Chicago, Illinois, United States, 60612
Contact: Mieoak Bahk    312-572-4543    mbahk@cookcountyhhs.org   
United States, Louisiana
LSU Health Baton Rouge Pulmonary Clinic Recruiting
Baton Rouge, Louisiana, United States, 70809
Contact: Jennifer Daigle    225-757-4150    jdai11@lsuhsc.edu   
United States, Maryland
John Hopkins University School of Medicine Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Study Coordinator    410-614-6702      
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Nicolas Issa    617-525-8418    NISSA@BWH.HARVARD.EDU   
United States, Michigan
Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Ines Hamilton    313-966-7284    ines.hamilton@med.wayne.edu   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Wendy Liang    412-648-6536    liangw3@upmc.edu   
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030-4009
Contact       gbaraujo@mdanderson.org   
United States, Washington
Fred Hutchinson Cancer Research Center Not yet recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
AiCuris Anti-infective Cures GmbH
Medpace, Inc.
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Responsible Party: AiCuris Anti-infective Cures GmbH
ClinicalTrials.gov Identifier: NCT03073967    
Other Study ID Numbers: AIC316-03-II-01
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Herpes Simplex
Disease Attributes
Pathologic Processes
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Foscarnet
Pritelivir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action