NCT03073967已完成3 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 140
- 主要终点
- Efficacy measured by cure rate
研究概览
简要总结
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 investigators choice, which can be either foscarnet 40 mg/kg every 8 hours or 60 mg/kg every 12 hours, or Cidofovir iv 5 mg/kg body weight given once weekly, or Cidofovir 1% or 3% topical applied 2 to 4 times daily, or Imiquimod 5% topical 3 times per week) (provided the drug is nationally approved).
详细描述
The trial comprises 5 Parts, Part A, B, C, D, E and F.
Part A and Part B (Phase 2) have been finalised.
- 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:
- present with foscarnet-resistance/intolerance, or
- 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).
Parts C, D, E and F (Phase 3).
- Part C is a randomized, open-label, multi-center, comparative design to assess the efficacy and safety of oral pritelivir in subjects with acyclovir resistent (ACV-R) mucocutaneous HSV episodes. Subjects with ACV-R mucocutaneous HSV infection will be randomized 1:1 to receive either oral pritelivir or Investigator's Choice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part C inclusion criteria
- •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.
- •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.
- •Lesions accessible for visual inspection to allow assessment of lesion healing including visualization by endoscopy.
- •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
- •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.
排除标准
- •Known resistance/intolerance to pritelivir or any of the excipients.
- •Previous treatment in PRIOH-
- •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.
- •Hemodialysis for any indication and ESRD (eGFR <15 mL/min; stage 5 CKD)
- •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 (complete) exclusion criteria
- •All exclusion criteria as for Part C, except criterion 12, which is replaced by:
- •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
- •Part D open for enrollment
研究组 & 干预措施
Part C, Pritelivir
Experimental
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
干预措施: Pritelivir (Drug)
Part D, Pritelivir
Experimental
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
干预措施: Pritelivir (Drug)
Part E, Pritelivir
Experimental
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
干预措施: Pritelivir (Drug)
Part F, Pritelivir
Experimental
Oral tablets, 100mg/day (400mg loading dose on day 1) for up to 28 days and potential prolongation for up to additional 14 days
干预措施: Pritelivir (Drug)
Part C,
Active Comparator
Investigator's Choice:
Foscarnet iv, 40 mg/kg tid or 60mg/kg bid or Cidofovir iv, 5 mg/kg body weight given once weekly or Cidofovir 1% or 3%, topically applied 2 to 4 times daily or Imiquimod 5%, topically applied 3 times per week, for up to 28 days and potential prolongation for up to additional 14 days.
干预措施: Investigator's choice (Drug)
结局指标
主要结局
Efficacy measured by cure rate
时间窗: 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.
次要结局
- Efficacy measured by cure rate(Up to a maximum of 42 days)
- Efficacy measured by time to lesion healing(Up to a maximum of 42 days)
- Efficacy measured by recurrence rate(At 3 months following post treatment visit, from randomization up to a maximum of 139 days)
- Efficacy measured by pain rate(Up to a maximum of 42 days)
- Efficacy measured by time to pain cessation at site of lesion(Up to a maximum of 42 days)
- Efficacy measured by average pain score(Up to a maximum of 42 days)
- Efficacy measured by clinical shedding rate(From date of randomization until the date of first documented healing, assessed up to a maximum of 42 days)
- Efficacy measured by time to cessation of shedding(Up to a maximum of 42 days)
- Efficacy measured by mean log number of HSV DNA copies(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Efficacy measured by resistance to trial medication(From date of randomization until the date of post treatment visit, assessed up to a maximum of 73 days)
- Safety measured by number of subjects developing chronic kidney disease(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing chronic kidney disease(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing acute Kidney Injury(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing renal impairment(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing electrolyte abnormality(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing seizures(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by percentage of subjects developing anemia(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by adverse events(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by haematology(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by lymphadenopathy(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by CRP (C reactive protein )(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by cutaneous adverse events(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by (a)PTT (partial thromboplastin time)(From date of randomization until the date of safety follow-up visit, assessed up to a maximum of 73 days)
- Safety measured by discontinuation rate(Up to a maximum of 42 days)
研究者
研究点 (140)
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