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

NCT ID: NCT03073967

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-08

Study Completion Date

2025-11-11

Brief Summary

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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

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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.

Conditions

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HSV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Pritelivir

Intervention Type DRUG

100 mg oral tablets

Part C,

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.

Group Type ACTIVE_COMPARATOR

Investigator's choice

Intervention Type DRUG

Foscarnet iv, 40 mg/kg BW tid or 60mg/kg bid or Cidofovir iv, 5 mg/kg BW given once weekly or Cidofovir 1% or 3%, topically applied 2 to 4 times daily or Imiquimod 5%, Solution for iv infusion or topical application

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

Group Type EXPERIMENTAL

Pritelivir

Intervention Type DRUG

100 mg oral tablets

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

Group Type EXPERIMENTAL

Pritelivir

Intervention Type DRUG

100 mg oral tablets

Part F, 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

Group Type EXPERIMENTAL

Pritelivir

Intervention Type DRUG

100 mg oral tablets

Interventions

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Pritelivir

100 mg oral tablets

Intervention Type DRUG

Investigator's choice

Foscarnet iv, 40 mg/kg BW tid or 60mg/kg bid or Cidofovir iv, 5 mg/kg BW given once weekly or Cidofovir 1% or 3%, topically applied 2 to 4 times daily or Imiquimod 5%, Solution for iv infusion or topical application

Intervention Type DRUG

Other Intervention Names

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Foscarnet or Cidofovir or Imiquimod

Eligibility Criteria

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Inclusion Criteria

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

In Canada, Germany, Belgium:

Immunocompromised (due to conditions including but not limited to HIV infection, hematopoietic cell or solid organ transplantation, and chronic use of immunosuppressive treatment) men and women of any ethnic group aged \>18 years.
2. ACV-R mucocutaneous HSV infection based on clinical failure 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 at doses equivalent to or greater than the local agency approved high oral doses of acyclovir, valacyclovir or famciclovir.
3. Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy.
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).



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 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)


2\. Recurrent mucocutaneous HSV infection considered ACV-S.

Exclusion Criteria

1. Known resistance/intolerance to pritelivir or any of the excipients.
2. Previous treatment in PRIOH-1.
3. Baseline safety laboratory abnormalities.
4. History or current evidence of gastrointestinal malabsorption which, in the opinion of the Investigator, may affect the extent of absorption of pritelivir.
5. Hemodialysis for any indication and ESRD (eGFR \<15 mL/min; stage 5 CKD)
6. History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other relevant diseases.
7. Abnormalities in hematological, clinical chemical or any other laboratory variables.
8. Not able to communicate meaningfully with the Investigator and site staff.
9. Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial.
10. Any other important local condition.
11. Pregnant and/or breastfeeding women.
12. Having received an investigational drug in an investigational drug trial unter certain conditions.


13. Having received an investigational drug in an investigational trial 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.



13\. Having used acyclovir, valacyclovir, or famciclovir within 3 days prior to starting pritelivir.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medpace, Inc.

INDUSTRY

Sponsor Role collaborator

AiCuris Anti-infective Cures AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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General Hospital of Athens - Laiko

Athens, , Greece

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Metro Infectious Disease Consultants, LLC - Huntsville

Hunstville, Alabama, United States

Site Status

University of South Alabama

Mobile, Alabama, United States

Site Status

University Arizona - Department of Medicine Arizona Health Sciences Center

Tuscon, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California, Division of Infectious Diseases

Sacramento, California, United States

Site Status

Midland Florida Clinical Research Center, LLC

DeLand, Florida, United States

Site Status

Midway Immunology and Research Center (MIRC)

Ft. Pierce, Florida, United States

Site Status

University of Florida (UF) - Division of Infectious Disease

Gainesville, Florida, United States

Site Status

Links Clinical Trials

Miami, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, United States

Site Status

Metro Infectious Disease Consultants - Atlanta

Decatur, Georgia, United States

Site Status

Metro Infectious Disease Consultants, LLC

Burr Ridge, Illinois, United States

Site Status

Department of Medicine J. H. Stroger Hospital of Cook County

Chicago, Illinois, United States

Site Status

LSU Health Baton Rouge Pulmonary Clinic

Baton Rouge, Louisiana, United States

Site Status

Tulane University - School of Medicine

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Lee's Summit MO United States 64086

Lee's Summit, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Kings Country Hospital Center

Brooklyn, New York, United States

Site Status

David H. Koch Center at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke University Medical Center - Division of Infectious Diseases

Durham, North Carolina, United States

Site Status

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Hospital Rawson

Córdoba, , Argentina

Site Status

Sanatorio Mayo Privado S.A.

Córdoba, , Argentina

Site Status

Instituto FIDES

La Plata, , Argentina

Site Status

Melbourne Health - Royal Melbourne Hospital

Parkville, , Australia

Site Status

Westmead Hospital, Centre for Infectious Disease and Microbiology

Westmead, , Australia

Site Status

AZ Sint-Jan Brugge

Bruges, , Belgium

Site Status

Centre Hospitalier Universitaire Saint Pierre

Brussels, , Belgium

Site Status

AZ Delta

Roeselare, , Belgium

Site Status

Alberta Health Services Cross Cancer Institute at the University of Alberta

Edmonton, Alberta, Canada

Site Status

CHU Limoges - Centre national de reference des Herpes virus

Limoges, , France

Site Status

CHU de Nantes

Nantes, , France

Site Status

Hôpital Saint Louis - AP-HP

Paris, , France

Site Status

AP-HP Hopital Necker-Enfants Malades

Paris, , France

Site Status

AP-HP Hopital Bichat - Claude Bernard

Paris, , France

Site Status

LLC Diakor

Tbilisi, , Georgia

Site Status

Multiprofile Clinic Consilium Medulla LTD

Tbilisi, , Georgia

Site Status

Universitätsklinikum Köln

Cologne, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status

Regional University General Hospital of Heraklion

Heraklion, , Greece

Site Status

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

Grande Ospedale Metropolitano "Bianchi Melacrino Morelli"

Calabria, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Unidad de Investigacion CIMA SC

Chihuahua City, , Mexico

Site Status

Centro de Investigacion Clinica GRAMEL S.C.

Distrito Federal, , Mexico

Site Status

Instituto de Investigaciones Aplicadas a la Neurociencia A.C

Durango, , Mexico

Site Status

Centro de Investigacion Farmaceutica Especializado de Occidente S.C.

Guadalajara, , Mexico

Site Status

Arke SMO S.A. de C.V.

Veracruz, , Mexico

Site Status

Universitaetsspital Basel

Basel, , Switzerland

Site Status

Hopitaux universitaires de Geneve

Geneva, , Switzerland

Site Status

Universitaetsspital Zuerich

Zurich, , Switzerland

Site Status

ARENSIA Exploratory Medicine LLC

Kyiv, , Ukraine

Site Status

Nhs Lothian

Edinburgh, , United Kingdom

Site Status

Research Department of Haematology, UCL Cancer Institute

London, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Canada France Georgia Germany Greece Israel Italy Mexico Switzerland Ukraine United Kingdom

Other Identifiers

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AIC316-03-II-01

Identifier Type: -

Identifier Source: org_study_id

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