PRIOH-1 Phase 3 (Part C, D, and E)

What is the Purpose of this Study?

Primary Objectives: - Part C: To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R mucocutaneous HSV infections for a treatment period of 28 days as a maximum in comparison to foscarnet given as intermittent iv (iv) infusions at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours for a minimum of one hour duration for a maximum treatment duration of 28 days - Part D: To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R and foscarnet-R/intolerant mucocutaneous HSV infections for a treatment period of 28 days as a maximum - Part E: To investigate the safety and tolerability of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-S mucocutaneous HSV infections for a treatment period of 28 days as a maximum Secondary Objectives: - To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R mucocutaneous HSV infections for a treatment period of 42 days as a maximum in comparison to foscarnet given as intermittent iv infusions at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours for a minimum of one hour duration for a maximum treatment duration of 42 days - To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R and foscarnet-R/intolerant mucocutaneous HSV infections for a treatment period of 42 days as a maximum - To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-S mucocutaneous HSV infections for a treatment period of 28 days as a maximum - To investigate the efficacy of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-S mucocutaneous HSV infections for a treatment period of 42 days as a maximum - To investigate the safety of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R mucocutaneous HSV infections for a treatment period of 28 days as a maximum in comparison to foscarnet given as intermittent iv infusions at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours for a minimum of one hour duration for a maximum treatment duration of 28 days - To investigate the safety of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R mucocutaneous HSV infections for a treatment period of 42 days as a maximum in comparison to foscarnet given as intermittent iv infusions at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours for a minimum of one hour duration for a maximum treatment duration of 42 days - To investigate the safety of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R and foscarnet-R/intolerant mucocutaneous HSV infections for a treatment period of 28 days as a maximum - To investigate the safety of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-R and foscarnet-R/intolerant mucocutaneous HSV infections for a treatment period of 42 days as a maximum - To investigate the safety of oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-S mucocutaneous HSV infections for a treatment period of 42 days as a maximum - To investigate the recurrence rate at 2 and 3 month following PoTV in all treatment groups in Part C, D and E - To investigate virology parameters such as viral shedding and resistance development to trial medication on treatment with oral pritelivir 100 mg once a day in immunocompromised subjects with ACV-S, ACV-R and foscarnet-R/intolerant mucocutaneous HSV infections for a treatment period of 42 days as a maximum

Eligibility

1. Immunocompromised men and women of any ethnic group aged ≥16 years.
In Canada, Germany, Belgium:

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.
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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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 infections in immunocompromised subjects

Study Details

Disease Type/Condition

Other

Principal Investigator

Zabner, Rachel

Age Group

Both

Phase

III

IRB Number

STUDY00001526

ClinicalTrials.gov ID

NCT03073967

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org