2023-506216-40-00招募中3 期
LUCY-1 - Letermovir/valganciclovir combination versus valganciclovir monotherapy for treatment of cytomegalovirus (CMV) infections in kidney transplant recipients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Virological response to treatment on Week-3, defined as a ≥ 2 log10 decrease of CMV DNAemia in whole blood from baseline, or an undetectable CMV DNAemia (< 200 IU/mL) in whole blood
研究概览
简要总结
To demonstrate that, compared to valganciclovir monotherapy, a letermovir + valganciclovir combination administered to kidney transplant recipients with CMV infection increases the proportion of patients reaching a virological response on Week-3 (defined as a ≥ 2 log10 decrease of CMV DNAemia from baseline or an undetectable CMV DNAemia (< 200 IU/mL) on Week 3).
研究设计
- 分配方式
- Randomized
- 主要目的
- Lucy-1
- 盲法
- Double (Subject, Investigator)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Informed consent and signed
- •Weight ≥ 30 kg
- •Kidney transplant recipient
- •Have a documented CMV infection or disease, with a screening value of CMV DNA ≥ 3000 IU/mL in whole blood or plasma in 2 consecutive assessments separated by ≥ 1 day, as determined by local laboratory quantitative polymerase chain reaction (qPCR). Both samples should be taken within 14 days prior to randomization with the second sample obtained within 5 days prior to randomization.
- •Eligible for treatment with oral valganciclovir, per investigator's judgment
- •For patients of childbearing age (following menarche): negative bHCG and effective method of contraception (sexual abstinence, hormonal contraception containing ethinylestradiol and levonorgestrel, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) until 30 days after the end of relevant systemic exposure (week 13). For male an effective method of contraception (sexual abstinence, condom) until 90 days after the end of relevant systemic exposure (week 13).
- •Have life expectancy of ≥ 8 weeks
- •French speaking
- •Affiliated to social security regime or an equivalent system
排除标准
- •Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to antiviral treatment, to the best knowledge of the investigator.
- •Have a CMV infection that is known to be genotypically resistant to valganciclovir and/or letermovir on documented evidence.
- •Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir or maribavir) for the current CMV infection for longer than 72 hours. However, patients experiencing CMV infection while receiving ganciclovir or valganciclovir prophylaxis (i.e. at prophylactic dosages) or letermovir prophylaxis can be included.
- •Have an eGFR < 15 mL/min/1.73m² (using the CKD-EPI Creatinine Equation (2009)).
- •Have serum aspartate aminotransferase (AST) ≥ 5 times higher than the upper limit of normal (ULN), or serum alanine aminotransferase (ALT) ≥ 5 times the ULN, or total bilirubin ≥ 3 times the ULN (except for documented Gilbert’s syndrome). Note: Subjects with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT ≥ 5 times ULN
- •Have a severe chronic liver disease (Child-Pugh Class C)
- •Have a known human immunodeficiency virus (HIV) infection with plasma HIV RNA ≥ 50 copies/mL within the 3 months before inclusion.
- •Require mechanical ventilation or vasopressors for hemodynamic support.
- •Be pregnant or breastfeeding.
- •Have an absolute neutrophil count less than 500 cells/µl, or platelet count less than 25,000/µl, or haemoglobin less than 8 g/dl
- •Have received anti-CMV vaccine at any time.
- •Be receiving leflunomide or artesunate when study treatment is initiated.
- •Be receiving strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat or St. John’s wort (Hypericum perforatum) when study treatment is initiated.
- •Be receiving efavirenz, etravirine, nevirapine, lopinavir, pimozine, ergot alkaloids, dabigatran, atorvastatine, (at a daily dose > 20mg, and/or if co-administered with cyclosporin A), pravastatin (if co-administered with cyclosporin A), simvastatine, rosuvastatine, pitavastatine or imipenem-cilastatine when study treatment is initiated.
- •Have known hereditary intolerance to galactose, with lactose Lapp deficiency, glucose or galactose malabsorption syndrome.
- •Have known hypersensitivity to letermovir or to an excipient for a study treatment.
- •Have any clinically significant medical or surgical condition that in the investigator’s opinion could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the subject.
- •Participation to another clinical trial on medicinal products for human use
结局指标
主要结局
Virological response to treatment on Week-3, defined as a ≥ 2 log10 decrease of CMV DNAemia in whole blood from baseline, or an undetectable CMV DNAemia (< 200 IU/mL) in whole blood
Virological response to treatment on Week-3, defined as a ≥ 2 log10 decrease of CMV DNAemia in whole blood from baseline, or an undetectable CMV DNAemia (< 200 IU/mL) in whole blood
次要结局
- Eradication of CMV DNAemia (< 200 IU/ml) before Week-12, detected in whole blood by quantitative CMV PCR every week until interruption of antiviral treatment, or at the latest until Week-12
- Number of days between baseline and first measure of CMV DNAemia < 200 IU/mL in whole blood.
- Absence of CMV-related symptoms at baseline and each visit.
- Clinical side effects, neutrophil, platelet, hemoglobin, creatinine, liver enzymes, bilirubin, urea tested every week until interruption of antiviral treatment (or at the latest until Week-12)
- Tablet count at each visit
- Sequencing of whole UL97, UL54, UL56, UL89 and UL51 genes in blood samples at baseline
- Sequencing of UL97, UL54, UL56, UL89 and UL51 genes at Week-3 or Week-12 (in patients achieving criteria defining “treatment failure”), and at any visit in patients presented with rebound of CMV DNAemia.
- Measurement of ganciclovir (in both groups) and letermovir (in the bitherapy arm) trough plasma concentration (Cmin) at Week-1, Cmin and Cmax at Week-2
- Measurement of the CMV specific T-cell immunity (by ELISpot-CMV) at baseline, Week-3, Week-6, Week-9 and Week-12.
研究者
Pierre FRANGE (Coordinating investigator)
Scientific
Assistance Publique Hopitaux De Paris
研究点 (6)
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