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

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 or positive genotypic/phenotypic resistance testing for current lesion.
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.