ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Adults (PRIOH-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03073967
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : February 5, 2019
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 mucocutaneous HSV infection, treated with pritelivir 100 mg qd (following a loading dose of 400 mg as first dose to rapidly reach steady-state plasma concentration) or foscarnet 40 mg/kg iv tid/60mg/kg iv bid.

Condition or disease Intervention/treatment Phase
HSV Infection Drug: Pritelivir Drug: Foscarnet Phase 2

Detailed Description:

The Trial comprises 2 Parts, Part A and Part B.

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).

Pritelivir trial medication, in both Part A and Part B, will be given orally as single daily doses of 100 mg (following a loading dose of 400 mg as first dose) until 7 days after the mucocutaneous HSV lesions are healed or up to a maximum of 28 days, whichever is earlier.

Foscarnet, in Part A, 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 7 days after the mucocutaneous HSV lesions are healed or up to a maximum of 28 days, whichever is earlier.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 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 Adults (PRIOH-1)
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Herpes Simplex

Arm Intervention/treatment
Experimental: Part A, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) over 4 weeks
Drug: Pritelivir
100 mg tablets

Active Comparator: Part A, Foscarnet
iv solution, 40 mg/kg tid or 60mg/kg bid.
Drug: Foscarnet
Solution for iv infusion

Experimental: Part B, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) over 4 weeks
Drug: Pritelivir
100 mg tablets




Primary Outcome Measures :
  1. Efficacy measured by time to lesion healing [ Time Frame: Up to a maximum of 28 days ]
    Complete epithelization of the mucocutaneous HSV lesion(s) assessed by lesion photography and no appearance of new lesions


Secondary Outcome Measures :
  1. Efficacy measured by time to lesion healing [ Time Frame: up to the last visit ]
    Time to lesion healing defined as complete epithelization of the mucocutaneous HSV lesion(s) up to the last visit, as assessed by lesion photography and no appearance of new lesions.

  2. Efficacy measured by average pain score [ Time Frame: Over 28 days ]
    Using a single-dimensional scale assessing pain intensity (NUMERIC RATING SCALE (NRS), 11 intensities: no pain to worst pain imaginable) through daily subject self-reporting

  3. Efficacy measured by pain rate [ Time Frame: Up to a maximum of 28 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

  4. Efficacy measured by time to pain cessation at site of lesion [ Time Frame: Up to a maximum of 28 days ]
    Starting at first dose of trial medication until pain is no longer reported by the subject (date and time)

  5. Efficacy measured by clinical shedding rate [ Time Frame: Until healing or up to a maximum of 28 days, whichever occurs first ]
    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)

  6. Efficacy measured by time to cessation of shedding [ Time Frame: Up to a maximum of 28 days ]
    Number of days until swabs taken are negative

  7. Efficacy measured by mean log number of HSV DNA copies [ Time Frame: 28 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).

  8. Efficacy measured by cure rate [ Time Frame: 28 days ]
    Number of subjects cured (lesion healed) at Day28 relative to the total number of subjects treated with pritelivir or foscarnet

  9. Efficacy measured by therapeutic failure rate [ Time Frame: 28 days ]
    Number of subjects with therapeutic failure under pritelivir or foscarnet treatment relative to the total number of subjects treated with pritelivir or foscarnet, respectively. Therapeutic failure is defined as: a) discontinuation and or replacement of trial medication due to failure of lesion healing and/or appearance of new lesion(s) post-healing within 28 days from the start of treatment or b) discontinuation of trial medication due to adverse event or intolerance to Trial medication before lesion healing or c) no lesion healing at 28 days from the start of treatment

  10. Efficacy measured by resistance to trial medication [ Time Frame: 28 days ]
    Genotypic and phenotypic resistance testing if lesion has not healed by Day 28, an additional swab will be taken.

  11. Efficacy measured by time to next recurrence [ Time Frame: Within 28 days after stop of trial medication ]
    In subjects with healed lesion(s).

  12. Safety measured by number of subjects developing acute Kidney Injury [ Time Frame: 28 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)


  13. Safety measured by number of subjects developing electrolyte abnormality [ Time Frame: 28 days ]
    All abnormal values

  14. Safety measured by number of subjects developing seizures [ Time Frame: 28 days ]
    All seizures

  15. Safety measured by number of subjects developing anemia [ Time Frame: 28 days ]
    Haemoglobin measurement

  16. Safety measured by adverse events [ Time Frame: 28 days ]
    Nature, frequency, duration, severity of and discontinuation due to adverse Events (AEs), seriousness, causality and outcome

  17. Safety measured by haematology [ Time Frame: 28 days ]
    Changes in all hematologic parameters

  18. Safety measured by lymphadenopathy [ Time Frame: 28 days ]
    Physical examination

  19. Safety measured by CRP (C reactive protein ) [ Time Frame: 28 days ]
    Increase

  20. Safety measured by cutaneous adverse events [ Time Frame: 28 days ]
    Physical examination

  21. Safety measured by (a)PTT (partial thromboplastin time) [ Time Frame: 28 days ]
    Increase

  22. Safety measured by discontinuation rate [ Time Frame: 28 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.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Part A, Inclusion Criteria:

  1. 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.
  2. Acyclovir resistant mucocutaneous HSV infection based on clinical failure (no improvement after at least 5 days with FDA approved high doses with acyclovir, valacyclovir or famciclovir) requiring switch to foscarnet treatment.
  3. Lesion accessible for size measurement and photography.
  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. Willing to use non-hormonal birth control: Male subjects who are surgically sterile (eg, after vasectomy) or who must agree to use an adequate method of contraception during participation in the trial and for at least 1 complete month after the final dose of trial medication. Female subjects who are surgically sterile (eg, 2-sided tubal ligation, resection or ovariectomy, hysterectomy) or post-menopausal (defined as at least 50 years of age and who have a history of no menses for at least 24 months) or female subjects of childbearing potential with no male partner, or use an adequate method of contraception during participation in the trial and for at least 1 complete month after the final dose of trial medication. An adequate method of contraception is defined as one of the following acceptable birth control methods:

    • the use of the copper-releasing intrauterine device (to have been in place for at least 2 months prior to screening)
    • the use of one of the following: diaphragm, Lea's shield, FemCap, sponge, and
    • monogamous relationship with vasectomized partner
    • the use of a male condom during each act of sexual intercourse.
  6. Subject must be willing and able (in the opinion of the investigator) to understand the informed consent form
  7. Negative serum β -HCG (beta human chorionic gonadotropin) test for female of child bearing potential at screening and a negative urine pregnancy test at Day 1.
  8. Subject must give written informed consent.

Part B, Inclusion criteria

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

2. ACV-resistant and foscarnet-resistant/intolerant mucocutaneous HSV infection based on clinical failure (no improvement after at least 5 days of foscarnet therapy or intolerance to foscarnet requiring cessation of foscarnet treatment) or result from genotypic/phenotypic testing.

Manifestations of foscarnet intolerance may include, renal function impairment, seizures, genital irritation and/or ulcerations, extremity paraesthesia, nausea, granulocytopenia, anemia, leukopenia, thrombopenia, hypokalemia, hypocalcemia, hypomagnesemia, diabetes insipidus, injection site reactions, psychotic disorders, including but not limited to anxiety and aggression.

Subjects entering Part B after cessation of foscarnet treatment in Part A will require a washout period of at least 3 days prior to starting pritelivir.

Part A, Exclusion criteria:

  1. Known intolerance to pritelivir and/or foscarnet or any of the excipients.
  2. Need to use drugs that have a narrow therapeutic index and are substrates for CYP2B6, CYP2C8, CYP2C9, CYP2C19, OATP1B1, OATP1B3, and OCT1 (organic cation transporter 1), ie warfarin, digoxin, phenytoin, paclitaxel, S-mephenytoin
  3. Baseline safety laboratory abnormalities: ANC (absolute neutrophil Count) < 1000 cells/mm3, platelet count < 25,000 cells/mm3, hemoglobin < 8.0 g/dL, AST (aspartate transaminase) or ALT (alanine transaminase) > 5 x ULN (upper Limit of normal), bilirubin > 2.5 x ULN
  4. History or current evidence of gastrointestinal malabsorption which, in the opinion of the investigator, may affect the extent of absorption of pritelivir.
  5. Severe renal insufficiency (GFR ≤ 29).
  6. History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other diseases, which, in the opinion of the investigator, may affect the subject's safety or interfere with the trial.
  7. Abnormalities in hematological, clinical chemical or any other laboratory variables at Screening measured by the central or local laboratory regarded as clinically relevant by the investigator unless they are due to underlying disease or condition.
  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 local condition including bacterial superinfection which in the opinion of the investigator would interfere with the efficacy evaluation.
  11. Pregnant and/or breastfeeding women.
  12. Having received an investigational drug in an investigational drug trial within the last 30 days before randomization for this clinical trial. Participation in a clinical trial without receiving other investigational drugs (e.g. follow-up phase of a trial, observational study) is permitted.

Part B, Exclusion criteria:

All exclusion criteria as for Part A, except for inclusion criteria 1 and 12 which are replaced by:

1. Known intolerance to pritelivir or any of the excipients and 12. Having received an investigational drug in an investigational drug trial within the last 30 days before Day 1 for this clinical trial (except for subjects entering Part B who have previously received foscarnet treatment in Part A of this trial). Participation in a clinical trial without receiving other investigational drugs (e.g. follow-up phase of a trial, observational study) is permitted.


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


Contacts
Contact: Medpace +1 513 579 9911 ext 24111 l.marsh@medpace.com

Locations
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, District of Columbia
Geogetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Maximiliano Menna    202-444-0371    mpm229@georgetown.edu   
United States, Florida
Midway Immunology and Research Center (MIRC) Recruiting
Fort Pierce, Florida, United States, 34982
Contact: Carly Sharp    772-595-9830    info@midwayresearch.com   
Comprehensive Care Center dba Community AIDs Network Recruiting
Sarasota, Florida, United States, 34237
Contact: Angela Ristuccia    941-366-0134 ext 11122    aristuccia@cancommunityhealth.org   
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
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Meredith Marshall    312-926-1076    meredith.marshall@northwestern.edu   
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   
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Cheryl Noss    773-702 ext 0727    cnussbalczo@medicine.bsd.uchicago.edu   
United States, Indiana
Indiana University (IU) Infectious Diseases Research Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Paula Johnson    317-274-8473    johnpaul@iu.edu   
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 Recruiting
Baltimore, Maryland, United States, 21287
Contact: Oyinkan Kusemiju    410-614-0648    Okusemi1@jhmi.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital 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
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Katelyn Clark    313-916-2613    kclark7@hfhs.org   
United States, New York
SUNY Downstate Medical Center Recruiting
Brooklyn, New York, United States, 11203
Contact: Michael Augenbraun    718-270-1432    Michael.Augenbraun@downstate.edu   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4009
Contact       CR_Study_Registration@mdanderson.org   
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
AiCuris Anti-infective Cures GmbH
Medpace, Inc.

Responsible Party: AiCuris Anti-infective Cures GmbH
ClinicalTrials.gov Identifier: NCT03073967     History of Changes
Other Study ID Numbers: AIC316-03-II-01
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Herpes Simplex
Infection
Communicable Diseases
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Acyclovir
Foscarnet
Phosphonoacetic Acid
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents