Informations générales (source: ClinicalTrials.gov)

NCT06334497 En recrutement IDF
Letermovir/Valganciclovir Combination Versus Valganciclovir Monotherapy for Treatment of Cytomegalovirus (CMV) Infections in Kidney Transplant Recipients
Interventional
  • Maladies transmissibles
  • Infections à cytomégalovirus
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
août 2024
novembre 2027
02 décembre 2025
The purpose of this study is to evaluate the efficacy and the tolerance of letermovir as part of dual antiviral therapy (in association with valganciclovir) in renal transplant recipients with CMV DNAemia, requiring valganciclovir treatment per investigator's judgment.
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Critères

Tous


1. Age ≥ 18 years

2. Weight ≥ 30 kg

3. Kidney transplant recipient

4. Have a documented CMV infection or disease, with (i) 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 OR (ii) a screening
value of CMV DNA ≥ 30000 IU/mL in whole blood or plasma, as determined by local
laboratory quantitative polymerase chain reaction (qPCR), in 1 sample obtained
within 5 days prior to randomization

5. Eligible for treatment with oral valganciclovir, per investigator's judgment

6. 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).

7. Have life expectancy of ≥ 8 weeks

8. French speaking

9. Affiliated to social security regime or an equivalent system

10. Informed consent and signed

Exclusion Criteria:


1. 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.

2. Have a CMV infection that is known to be genotypically resistant to valganciclovir
and/or letermovir on documented evidence.

3. 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.

4. Have an eGFR < 30 mL/min/1.73m² (using the CKD-EPI Creatinine Equation (2009)).

5. 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

6. Have a severe chronic liver disease (Child-Pugh Class C)

7. Have a known human immunodeficiency virus (HIV) infection with plasma HIV RNA ≥ 50
copies/mL within the 3 months before inclusion.

8. Require mechanical ventilation or vasopressors for hemodynamic support.

9. Be pregnant or breastfeeding.

10. Have received anti-CMV vaccine at any time.

11. Be receiving leflunomide or artesunate when study treatment is initiated.

12. 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.

13. Be receiving efavirenz, etravirine, nevirapine, lopinavir, pimozine, ergot
alkaloids, dabigatran, atorvastatine, simvastatine, rosuvastatine, pitavastatine or
imipenem-cilastatine when study treatment is initiated.

14. Have known hereditary intolerance to galactose, with lactose Lapp deficiency,
glucose or galactose malabsorption syndrome.

15. Have known hypersensitivity to letermovir or to an excipient for a study treatment.

16. 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.

17. Participation to another clinical trial on medicinal products for human use

18. 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