Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (PRIOH-1)
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| ClinicalTrials.gov Identifier: NCT03073967 |
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Recruitment Status :
Recruiting
First Posted : March 8, 2017
Last Update Posted : June 1, 2023
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Sponsor:
AiCuris Anti-infective Cures AG
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
AiCuris Anti-infective Cures AG
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Brief Summary:
Randomized, open-label, multi-center, comparative trial to assess the efficacy and safety in immunocompromised subjects with acyclovir resistant or acyclovir susceptible mucocutaneous HSV infection, treated with pritelivir 100 mg once daily (following a loading dose of 400 mg as first dose to rapidly reach steady-state plasma concentration) or foscarnet 40 mg/kg every 8 hours or 60 mg/kg every 12 hours.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HSV Infection | Drug: Pritelivir Drug: Foscarnet | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 153 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 (Herpes Simplex Virus) Infections in Immunocompromised Subjects (PRIOH-1) |
| Actual Study Start Date : | May 8, 2017 |
| Estimated Primary Completion Date : | June 2024 |
| Estimated Study Completion Date : | October 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Herpes Simplex
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part C, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
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Drug: Pritelivir
100 mg tablets |
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Active Comparator: Part C, Foscarnet
iv solution, 40 mg/kg tid or 60mg/kg bid for up to 28 days and potential prolongation for up to additional 14 days.
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Drug: Foscarnet
Solution for iv infusion |
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Experimental: Part D, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
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Drug: Pritelivir
100 mg tablets |
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Experimental: Part E, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
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Drug: Pritelivir
100 mg tablets |
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Experimental: Part F, Pritelivir
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
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Drug: Pritelivir
100 mg tablets |
Primary Outcome Measures :
- Efficacy measured by cure rate [ Time Frame: Up to a maximum of 28 days ]Number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 28 days relative to the total number of subjects treated with trial medication in the respective treatment group.
Secondary Outcome Measures :
- Efficacy measured by cure rate [ Time Frame: Up to a maximum of 42 days ]Number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 42 days relative to the total number of subjects treated with trial medication in the respective treatment group.
- Efficacy measured by time to lesion healing [ Time Frame: Up to a maximum of 42 days ]Time to lesion healing, defined as complete epithelization of the mucocutaneous HSV lesion(s) within the treatment period and no appearance of new lesions, as assessed by the Investigator.
- Efficacy measured by recurrence rate [ Time Frame: At 2 months following post treatment visit, from randomization up to a maximum of 108 days ]Recurrence rate at 2 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment.
- Efficacy measured by recurrence rate [ Time Frame: At 3 months following post treatment visit, from randomization up to a maximum of 139 days ]Recurrence rate at 3 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment.
- Efficacy measured by pain rate [ Time Frame: Up to a maximum of 42 days ]Number of days with pain at lesion site relative to the total number of days with analyzable pain data through daily subject self-reporting
- Efficacy measured by time to pain cessation at site of lesion [ Time Frame: Up to a maximum of 42 days ]Starting at first dose of trial medication until pain is no longer reported by the subject (date and time)
- Efficacy measured by average pain score [ Time Frame: Up to a maximum of 42 days ]Using a single-dimensional scale assessing pain intensity through daily subject self-reporting
- Efficacy measured by clinical shedding rate [ Time Frame: From date of randomization until the date of first documented healing, assessed up to a maximum of 42 days ]Number of HSV positive swabs per subject relative to the total number of swabs collected per subject from lesion swabs taken from HSV lesion(s)
- Efficacy measured by time to cessation of shedding [ Time Frame: Up to a maximum of 42 days ]Number of days until swabs taken are negative
- Efficacy measured by mean log number of HSV DNA copies [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Mean log number of HSV DNA copies on HSV DNA positive swabs from lesion(s) as detected by quantitative real-time PCR (polymerase chain reaction).
- Efficacy measured by resistance to trial medication [ Time Frame: From date of randomization until the date of post treatment visit, assessed up to a maximum of 73 days ]Resistance to trial medication for lesions not healed within the treatment period or newly appeared lesions under treatment before or at the PoTV.
- Safety measured by number of subjects developing chronic kidney disease [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Chronic kidney disease
- Safety measured by percentage of subjects developing chronic kidney disease [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Chronic kidney disease
- Safety measured by number of subjects developing acute Kidney Injury [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Acute Kidney Injury (AKI) stage >1 of KDIGO (Kidney Disease: Improving Global Outcome) criteria (increase in serum creatinine by 2.0 to 2.9 times compared to baseline or urine output <0.5 mL/kg/h for >12 hours)
- Safety measured by number of subjects developing renal impairment [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Renal impairment
- Safety measured by percentage of subjects developing renal impairment [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Renal impairment
- Safety measured by number of subjects developing electrolyte abnormality [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]All abnormal values
- Safety measured by number of subjects developing seizures [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]All seizures
- Safety measured by number of subjects developing anemia [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Haemoglobin measurement
- Safety measured by adverse events [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of Adverse Events
- Safety measured by haematology [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of abnormal hematologic laboratory test results
- Safety measured by lymphadenopathy [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of lymphadenopathy measured by physical examination
- Safety measured by CRP (C reactive protein ) [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of CRP increase
- Safety measured by cutaneous adverse events [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of cutaneous adverse events by physical examination
- Safety measured by (a)PTT (partial thromboplastin time) [ Time Frame: From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days ]Incidence of (a)PTT increase
- Safety measured by discontinuation rate [ Time Frame: Up to a maximum of 42 days ]Number of subjects discontinuing pritelivir or foscarnet due to AE(s) or intolerance relative to the total number of subjects treated with pritelivir or foscarnet, respectively
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Part C inclusion criteria
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Immunocompromised men and women of any ethnic group aged ≥16 years.
In Canada, Germany, Belgium:
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.
- ACV-R mucocutaneous HSV infection based on clinical failure, requiring switch to foscarnet treatment 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 withat doses equivalent to or greater than the local agency approved high oral doses withof acyclovir, (800 mg TID) or valacyclovir or famciclovir.(1 g TID).
- Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy or pharyngoscopy.
- 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.
- Willingness to use highly effective birth control.
- 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.
- 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.
- 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
- Known resistance/intolerance to pritelivir and/or foscarnet or any of the excipients.
- Previous treatment in PRIOH-1.
- Need to use paclitaxel.
- Baseline safety laboratory abnormalities.
- History or current evidence of gastrointestinal malabsorption which, in the opinion of the Investigator, may affect the extent of absorption of pritelivir.
- Severe renal insufficiency (eGFR ≤29 mL/min/1.73 m2).
- History or current evidence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other relevant diseases.
- Abnormalities in hematological, clinical chemical or any other laboratory variables.
- Not able to communicate meaningfully with the Investigator and site staff.
- Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial.
- Any other important local condition.
- Pregnant and/or breastfeeding women.
- Having received an investigational drug in an investigational drug trial unter certain conditions.
Part D exclusion criteria
All exclusion criteria as for Part C, except for exclusion criterion 1, which is replaced by: 1. Known intolerance to pritelivir or any of the excipients and except criterion 13, which is replaced by: 13. Having received an investigational drug in an investigational drug 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 as for Part C, except for exclusion criteria 1, which is replaced by
1. known intolerance to pritelivir or any of the excipients and addition of 14. Having used (val)acyclovir within 3 days prior to starting pritelivir.
Part F exclusion criteria All exclusion criteria for Part D plus 14. Part D open for enrollment
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03073967
Locations
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Sponsors and Collaborators
AiCuris Anti-infective Cures AG
Medpace, Inc.
| Responsible Party: | AiCuris Anti-infective Cures AG |
| ClinicalTrials.gov Identifier: | NCT03073967 |
| Other Study ID Numbers: |
AIC316-03-II-01 |
| First Posted: | March 8, 2017 Key Record Dates |
| Last Update Posted: | June 1, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Pritelivir Infections Communicable Diseases Herpes Simplex Disease Attributes Pathologic Processes Herpesviridae Infections DNA Virus Infections Virus Diseases Skin Diseases, Viral |
Skin Diseases, Infectious Skin Diseases Foscarnet Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |