A randomized, open-label, multicenter, comparative study to assess the efficacy and safety of Pritelivir for the treatment of acyclovir-resistant mucocutaneous herpes simplex infections in immunocompromised patients (PRIOH-1)
Summary description of the study
Part C has a randomized, open-label, multicenter, comparative design to assess the efficacy and safety of oral Pritelivir in patients with episodes of acyclovir-resistant mucocutaneous HSV infection. Patients with acyclovir-resistant mucocutaneous HSV infection are randomized in a 1:1 ratio to receive treatment with oral Pritelivir or i.v. Foscarnet. The study aims to demonstrate the superiority of Pritelivir over Foscarnet in achieving clinical healing based on the number of patients whose lesions have healed within 28 days. Part D has an open-label, multicenter design (within the same study as Part C) to assess the efficacy and safety of Pritelivir in patients with episodes of acyclovir-resistant mucocutaneous HSV infection who also have the following characteristics: 1. Presence of resistance/intolerance to Foscarnet already at screening for study enrollment or 2. Development of resistance/intolerance to Foscarnet during treatment in Part C or treatment failure (discontinuation of Foscarnet after at least 7 days of treatment due to worsening of the lesion(s) and/or the occurrence of new lesions). Part E has an open-label, multicenter design (within the same study as Part C) to assess the efficacy and safety of Pritelivir in patients with episodes of acyclovir-sensitive mucocutaneous HSV infection. Part E will not be conducted in Germany. Part F has an open-label, multicenter design (within the same study as Part C) to assess the efficacy and safety of Pritelivir in patients with episodes of acyclovir-resistant mucocutaneous HSV infection who also have one of the following characteristics: (see protocol)
(BASEC)
Intervention under investigation
Parts C, D, E, and F The investigational product Pritelivir is administered orally in all parts (C, D, E, and F) in daily single doses of 100 mg (after a loading dose of 400 mg as the first dose) until all mucocutaneous HSV lesions are healed, or for a maximum of 28 days, whichever occurs first. Foscarnet is administered in Part C as intermittent infusions of at least 1 hour at a dose of 40 mg/kg every 8 hours or 60 mg/kg every 12 hours (dose adjustment in case of renal impairment) until all mucocutaneous lesions are healed, or for a maximum of 28 days, whichever occurs first. If the lesions are in the process of healing at the end of the 28-day treatment phase but are not yet fully healed, and the investigator believes that extending treatment will lead to complete healing, the investigational product may be continued for up to a maximum of 14 additional days. The patients in question will be considered treatment failures for the primary endpoint, but the efficacy outcome of these patients will be included in the secondary efficacy analysis. In Parts C, D, and F, the ACV-R and/or Foscarnet-R status is documented by genotyping. If the results of genotyping for ACV-R or Foscarnet-R are negative or inconclusive, phenotyping will be performed.
(BASEC)
Disease under investigation
Acyclovir-resistant mucocutaneous herpes simplex infections in immunocompromised patients (PRIOH-1)
(BASEC)
Immunocompromised men and women (due to conditions such as HIV infection, hematopoietic stem cell or solid organ transplantation, and chronic glucocorticoid use) of any ethnic origin aged > 16 years in Canada, Germany, Belgium: Immunocompromised men and women (due to conditions such as HIV infection, hematopoietic stem cell or solid organ transplantation, and chronic glucocorticoid use) of any ethnic origin aged > 18 years. 2. ACV-R mucocutaneous HSV infection based on clinical treatment failure requiring a switch to Foscarnet treatment, or a positive genotypic/phenotypic ACV resistance test for the current lesion. Clinical treatment failure is defined as no improvement after oral or i.v. dosing for at least 7 days at doses corresponding to or exceeding those approved by the national drug authority for oral high doses of Acyclovir (800 mg t.i.d. [three times daily]) or Valacyclovir (1 g t.i.d.). 3. Accessibility of the lesions for visual inspection to allow assessment of lesion healing, including visualization by endoscopy or pharyngoscopy. 4. Willingness to refrain from using lotions and/or creams in the area with HSV lesions. Moist/dry dressings or bandages with saline on the lesions are allowed. 5. Willingness to use highly effective contraceptive methods: Male study participants must be surgically sterilized (e.g., by vasectomy at least 26 weeks prior to treatment initiation) or must agree to use an appropriate form of contraception during sexual intercourse with fertile women (see definition below) to ensure that conception of a child during treatment and for at least 6 months after the last administration of the investigational product is avoided. Non-fertile female study participants must either be surgically sterilized (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks prior to treatment initiation) or postmenopausal (defined as spontaneous amenorrhea for at least 2 years, with a follicle-stimulating hormone [FSH] concentration in the postmenopausal range at treatment initiation). Fertile women must use an appropriate form of contraception (see definition below). An appropriate form of contraception is defined as a highly effective contraceptive method plus the use of a condom during participation in this study and for at least 6.5 months after the last administration of the investigational product. Highly effective contraceptive methods are: o Copper IUD o Levonorgestrel-releasing intrauterine system o Progesterone implant o Hormonal combination preparation (containing estrogen and progesterone) that inhibits ovulation: oral, intravaginal, transdermal o Hormonal contraceptive based on pure progesterone that inhibits ovulation: oral, injected, implanted. (see protocol) (BASEC)
Exclusion criteria
Exclusion criteria for Part C 1. Known resistance/intolerance to Pritelivir and/or i.v. Foscarnet or any of the excipients 2. Previous treatment in PRIOH-1 3. Need for Paclitaxel 4. Abnormalities in baseline safety laboratory values: 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 5. History or current evidence of gastrointestinal malabsorption that in the opinion of the investigator could affect the absorption of Pritelivir 6. Severe renal insufficiency (eGFR ≤ 29 ml/min/1.73 m2) 7. History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, metabolic, neurological, psychiatric, or other disease that in the opinion of the investigator could compromise patient safety or interfere with study conduct 8. Abnormalities in laboratory values for hematology or clinical chemistry or other laboratory values determined by the local or central laboratory at screening, deemed clinically relevant by the investigator, unless due to the underlying disease. 9. Patients unable to communicate meaningfully with the investigator and study center staff 10. Presence of any other disease/disorder that in the opinion of the investigator would compromise the successful completion of this clinical study 11. Presence of any other local disease, including bacterial superinfection, that in the opinion of the investigator would compromise the assessment of efficacy 12. Pregnant and/or breastfeeding women 13. Treatment with a drug in clinical trial that has not occurred more than 7 half-lives of the drug in question at the time of treatment initiation with the investigational product. Current participation in a clinical trial without receiving other investigational drugs (e.g., post-study follow-up phase, observational study) is allowed. Exclusion criteria for Part D All exclusion criteria for Part C, except exclusion criteria 1 and 13, which are replaced by the following criteria: 1. Known intolerance to Pritelivir or any of the excipients and 13. Treatment with a drug in clinical trial that has not occurred more than 7 half-lives of the drug in question at the time of treatment initiation with the investigational product, except for patients who switch from Part C to Part D after previous treatment with Foscarnet in this study. Current participation in a clinical trial without receiving other investigational drugs (e.g., post-study follow-up phase, observational study) is allowed. Exclusion criteria for Part E (Part E will not be conducted in Germany) All inclusion criteria that also apply to Part C, except for inclusion criterion 1, which is replaced by: 1. Known intolerance to Pritelivir or any of the other components and 14. Use of (Val)Acyclovir in the 3 days prior to the start of treatment with Pritelivir. Exclusion criteria for Part F All inclusion criteria that also apply to Part D, and additionally 14. Part D open for recruitment (BASEC)
Trial sites
Basel, Geneva, Zurich
(BASEC)
Sponsor
Sponsor: AiCuris Anti-infective Cures AG, Friedrich-Ebert-Str. 475, 42117 Wuppertal, Deutschland („AiCuris“) Sponsor's Representative in CH: Medpace Switzerland AG c/o BDO AG 4052 Basel Switzerland
(BASEC)
Contact
Contact Person Switzerland
Nicolas Johannes Müller
+4112553712
Nicolas.Mueller@clutterusz.chUniversitaetsspital Zuerich Klinik für Infektionskrankheiten und Spitalhygiene Rämistrasse 100 8091 Zürich
(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
04.02.2022
(BASEC)
ICTRP Trial ID
NCT03073967 (ICTRP)
Official title (approved by ethics committee)
A randomized, open-label, multi-center, comparative trial, to assess the efficacy and safety of pritelivir for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised subjects (PRIOH-1) (BASEC)
Academic title
A Randomized, Open Label, Multi-center, Comparative Trial, to Assess the Efficacy and Safety of Pritelivir for the Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (PRIOH-1) (ICTRP)
Public title
Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (ICTRP)
Disease under investigation
HSV Infection (ICTRP)
Intervention under investigation
Drug: PritelivirDrug: Investigator's choice (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Part C inclusion criteria
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 -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).
Part D and F inclusion criteria
All inclusion criteria as for 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.
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)
All inclusion criteria as for Part C, except for inclusion criterion 2, which is replaced
by:
2. Recurrent mucocutaneous HSV infection considered ACV-S.
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.
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.
Part D (complete) exclusion criteria
All exclusion criteria as for Part C, except criterion 12, which is replaced by:
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.
Part E exclusion criteria (Part E is not being conducted in Germany)
All exclusion criteria in Part E are identical to those in Part C with the addition of:
13. Having used acyclovir, valacyclovir, or famciclovir within 3 days prior to starting
pritelivir.
Part F exclusion criteria All exclusion criteria for Part D plus 13. Part D open for
enrollment (ICTRP)
not available
Primary and secondary end points
Efficacy measured by cure rate (ICTRP)
Efficacy measured by cure rate;Efficacy measured by time to lesion healing;Efficacy measured by recurrence rate;Efficacy measured by recurrence rate;Efficacy measured by pain rate;Efficacy measured by time to pain cessation at site of lesion;Efficacy measured by average pain score;Efficacy measured by clinical shedding rate;Efficacy measured by time to cessation of shedding;Efficacy measured by mean log number of HSV DNA copies;Efficacy measured by resistance to trial medication;Safety measured by number of subjects developing chronic kidney disease;Safety measured by percentage of subjects developing chronic kidney disease;Safety measured by percentage of subjects developing acute Kidney Injury;Safety measured by percentage of subjects developing renal impairment;Safety measured by percentage of subjects developing electrolyte abnormality;Safety measured by percentage of subjects developing seizures;Safety measured by percentage of subjects developing anemia;Safety measured by adverse events;Safety measured by haematology;Safety measured by lymphadenopathy;Safety measured by CRP (C reactive protein );Safety measured by cutaneous adverse events;Safety measured by (a)PTT (partial thromboplastin time);Safety measured by discontinuation rate (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
Medpace, Inc. (ICTRP)
Additional contacts
not available
Secondary trial IDs
AIC316-03-II-01 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03073967 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available