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

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.

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.