Combination Letermovir and Standard of Care Antiviral for Enhanced Antiviral Response in Cytomegalovirus Infection in Lung Transplant Recipients

NCT07235683 | Recruiting Phase 4

• 1 other identifier: 25-5760
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the CLEAR-CMV trial is to evaluate the efficacy of letermovir therapy plus standard of care (SOC) antiviral compared to SOC plus placebo in achieving clearance of CMV viremia by week 3 in lung transplant recipients with active CMV infection.

Conditions

Lung Transplant Recipient; CMV

Keywords

CMV Disease; Lung Transplant

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving clearance of CMV viremia by week 3, as measured by quantitative PCR.

  Viral clearance is described by a plasma CMV viral load \< 200 IU/mL, the UHN clinically used threshold

  From time of enrollment until 3 weeks after enrolment

Secondary Outcomes (8)

• Proportion of patients achieving an undetectable viral load

  At week 3 and by month 6 after enrolment

• Proportion of patients achieving CMV viral load <137 IU/mL (lower limit of quantification of the assay)

  At week 3 from enrolment and at 6 months

• Time to clearance of CMV viremia

  From enrolment until clearance of CMV viremia, up to 6 months after enrolment

• Time to resolution of symptoms if present

  From enrolment until clearance of symptoms, up to 6 months after enrolment

• Development of antiviral resistance

  From enrolment until up to 6 months after enrolment

Study Arms (2)

SOC antiviral plus placebo

PLACEBO COMPARATOR

Patients will receive the standard of care (SOC) antiviral therapy along with a placebo drug. The placebo drug will be administered for three weeks, while the SOC antiviral duration and dosage will be at the discretion of the treating physician.

Drug: Placebo; Drug: Valganciclovir/Ganciclovir

SOC antiviral plus letermovir active drug

EXPERIMENTAL

Patients will receive the standard of care (SOC) antiviral therapy in combination with letermovir. The letermovir active drug will be administered for three weeks, while the SOC antiviral treatment duration and dosage will be at the discretion of the treating physician.

Drug: Letermovir; Drug: Valganciclovir/Ganciclovir

Interventions

Letermovir DRUG

Letermovir (480mg) will be given orally as a loading dose every 12 hours for the first 24 hours, then one tablet per day for a total treatment duration of 21 days. Letermovir treatment will be started within 72 hours of starting SOC antiviral treatment as per the decision of the treating physician.

SOC antiviral plus letermovir active drug

Placebo DRUG

Placebo will be dosed the same as letermovir: one tablet every 12 hours for the first 24 hours, then one tablet per day for total treatment duration of 21 days.

SOC antiviral plus placebo

Valganciclovir/Ganciclovir DRUG

Ganciclovir or its oral prodrug, valganciclovir will be administered as the standard of care antiviral therapy. Its duration will be at the discretion of the treatment physician but is typically given until clearance of viremia. The clinical definition of viral clearance is one negative viral load or two viral loads one week apart that are \<200 IU/mL

SOC antiviral plus letermovir active drug; SOC antiviral plus placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient of a lung transplant.
• Has confirmed CMV viremia with a viral load ≥ 1000 IU/mL and will receive or has just started SOC antiviral treatment in the past 72h as per the decision of the treating physician.

You may not qualify if:

• Renal failure with Creatinine clearance \<15 mL/min or requiring dialysis
• Severe hepatic impairment (Child-Pugh Class C)
• Participating in another interventional clinical trial
• Combined transplant (e.g heart-lung, lung-liver)
• Known allergy or contraindication to any of the antiviral medications
• Known antiviral resistance.
• Patient receiving cyclosporin, pimozide or ergot alkaloids (due to significant drug interaction with letermovir).
• Patient receiving or expected to receive CMV immunoglobulin or IVIG during the initial three week treatment phase

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Interventions

letermovir; Valganciclovir; Ganciclovir

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Atul Humar, MD, FRCPC

CONTACT

416-340-4241; atul.humar@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 19, 2025
• Study Start: December 24, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

CA (1)