A clinical trial to assess the efficacy and safety of pritelivir for the treatment of Herpes Simplex Virus infections on the skin and mucous membranes which is resistant to acyclovir in subjects with weakened immune system.
- Conditions
- Acyclovir-resistant mucocutaneous HSV infections in immunocompromised subjectsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-004940-27-DE
- Lead Sponsor
- AiCuris Anti-infective Cures AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 153
Part C inclusion criteria
1. 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 doses of acyclovir, valacyclovir or Famciclovir.
3. Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy.
4. Willing to use highly effective birth control:
Male subjects must be surgically sterile (eg, vasectomy at least for the 26 weeks before starting treatment) or must agree to use an adequate method of contraception during sexual intercourse with women of childbearing potential to make sure the fathering of a child will be ruled out during treatment and for at least 6 months after the final dose of trial medication. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before starting treatment) or postmenopausal (defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at start of treatment). Female subjects of childbearing potential must use an adequate method of contraception.
An adequate method of contraception is defined as a highly effective method of contraception plus use of a condom during participation in this trial and for at least 6,5 months after the final dose of trial medication. A highly effective method of contraception is defined as:
o copper intrauterine device,
o the levonorgestrel-releasing intrauterine system,
o the progestogen implant,
o combined (estrogen and progestogen containing) hormonal contraception (oral,
intravaginal, transdermal) associated with inhibition of ovulation,
o progestogen-only hormonal contraception (oral, injectable, implantable) associated
with inhibition of ovulation.
5. Subject, and/or their legally authorized representative (proxy consent is not permitted in Germany) must be willing and able (in the opinion of the Investigator) to understand the Informed Consent Form.
6. Negative serum ß-HCG (beta-human chorionic gonadotropin) test for women of childbearing potential at Screening and a negative urine pregnancy test at Day 1.
7. Subject must give 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).
Part D (complete) and F:
Inclusion criteria in Part D are identical to those in Part C, except for inclusion criterion 2 which is replaced by:
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. Clinical failure of ACV treatment 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 doses of acyclovir, valacyclovir, or famciclovir.
Part C exclusion criteria
1. Known resistance/intolerance to pritelivir or any of the excipients.
2. Previous treatment in PRIOH-1
3. Baseline safety laboratory abnormalities:
o ANC <1000 cells/mm3
o platelet count <25,000 cells/mm3
o hemoglobin <8.0 g/dL
o AST or ALT >5 x ULN
o 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. 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 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 7 half-lives after the last administration of this drug before initiating trial medication. Current participation in a clinical trial without receiving other investigational drugs (eg, follow-up phase of a trial, observational study) is permitted. Other investigational drugs are also not permitted during participation in this trial.
Part D (complete)
All exclusion criteria as for Part C, except for exclusion 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 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.
Part F
All exclusion criteria for Part D plus
13. Part D open for enrollment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method