Letermovir for Cytomegalovirus

(CLEAR-CMV Trial)

Overseen By Atul Humar, MD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University Health Network, Toronto

Must be taking: Antivirals

Must not be taking: Cyclosporin, Pimozide, Ergot alkaloids

Disqualifiers: Renal failure, Severe hepatic impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called letermovir to determine its effectiveness in clearing cytomegalovirus (CMV) infection in lung transplant recipients. Researchers aim to find out if adding letermovir to the usual antiviral treatment is more effective than using a placebo. Individuals who have had a lung transplant and have an active CMV infection may qualify for this study. Participants will receive either letermovir with their standard antiviral treatment or a placebo with their standard treatment for three weeks. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how letermovir can benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications like cyclosporin, pimozide, or ergot alkaloids because they can interact with the trial drug, letermovir. If you're on these medications, discuss with your doctor before joining the trial.

What is the safety track record for letermovir?

Research has shown that letermovir is safe and effective for both children and adults. Studies have demonstrated its efficacy in preventing cytomegalovirus (CMV) infections with minimal side effects. For instance, a study with children found letermovir both effective and safe for CMV prevention. Another study examining its use in real-life situations confirmed its safety for teenagers. This evidence indicates that letermovir has a strong safety record across different age groups.

Overall, patients have tolerated letermovir well, with only a few minor side effects reported. This makes it a promising option for preventing CMV infections. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for cytomegalovirus (CMV) involve standard antiviral drugs like ganciclovir or valganciclovir. Letermovir is unique because it specifically targets the CMV terminase complex, a different mechanism from the typical DNA polymerase inhibition seen with other antivirals. This distinction means it can be used alongside standard treatments without overlapping side effects. Researchers are excited about letermovir because it offers a promising option for patients who may not tolerate conventional therapies well, potentially reducing the risk of resistance and improving overall outcomes.

What evidence suggests that letermovir might be an effective treatment for CMV?

Research has shown that letermovir can reduce problems caused by cytomegalovirus (CMV) infections, especially in transplant recipients. Studies have found it to be safe and effective, significantly lowering the risk of CMV infections. Specifically, letermovir has prevented CMV disease in heart transplant patients. In this trial, participants will receive either the standard of care (SOC) antiviral therapy with letermovir or SOC antiviral therapy with a placebo. Early use of letermovir can also strengthen the immune system's T-cell response, aiding in infection defense. These findings suggest that letermovir can effectively treat CMV in lung transplant patients. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for lung transplant recipients who are currently experiencing active Cytomegalovirus (CMV) infection. Participants should meet specific health criteria and not be taking certain medications that could interfere with the study.

Inclusion Criteria

I have received a lung transplant.

I have a CMV infection with a viral load over 1000 IU/mL and am starting standard antiviral treatment.

Exclusion Criteria

My liver is severely damaged.

Participating in another interventional clinical trial

I am receiving or will receive CMV immunoglobulin or IVIG in the first three weeks of treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SOC antiviral therapy in combination with letermovir or placebo for three weeks

3 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and viral clearance after treatment

6 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Letermovir

Trial Overview The CLEAR-CMV trial is testing if adding Letermovir to standard antiviral treatments like Valganciclovir or Ganciclovir helps clear CMV faster by week 3 compared to just the standard treatment plus a placebo.

How Is the Trial Designed?

Group I: SOC antiviral plus letermovir active drug Experimental Treatment 2 Interventions

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.

Group II: SOC antiviral plus placebo Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879759/

Real-World Outcomes Associated With Letermovir Use for ... Letermovir for CMV PP was effective in reducing the risk of CMV-related complications overall and mortality beyond day 200 among adult allo-HCT recipients.

2. nature.com nature.com/articles/s41598-025-27490-z

Early CMV DNAemia during letermovir prophylaxis predicts ... In conclusion, early abortive CMV DNAemia during letermovir prophylaxis appears to induces rapid and durable T-cell immunity. Immune monitoring ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916425002842

Efficacy of Letermovir for Cytomegalovirus Prophylaxis in ... Cytomegalovirus (CMV) prophylaxis post–heart transplantation with letermovir appears to be effective in preventing CMV disease. •. Most patients ...

4. frontiersin.org frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1558637/full

Real-world efficacy and safety of letermovir versus ... In this single-center real-world study, letermovir exhibited a favourable efficacy and safety profile for CMV prophylaxis in adolescent patients undergoing ...

5. journalofinfection.com journalofinfection.com/article/S0163-4453(24)00154-3/fulltext

Real-world experience with letermovir for cytomegalovirus ... The incidence of CMV infections was significantly reduced by letermovir. •. Almost half of CMV infections occurred after letermovir ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40529478

Efficacy and Safety of Letermovir for Cytomegalovirus ... Conclusion: Letermovir is both effective and safe for CMV prophylaxis in pediatric patients following HCT, especially in patients with more risk ...

7. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(23)00344-7/abstract

Efficacy and safety of extended duration letermovir ... We aimed to evaluate the efficacy and safety of extending the duration of letermovir prophylaxis for clinically significant cytomegalovirus infection from 100 ...

8. journals.asm.org journals.asm.org/doi/10.1128/aac.00420-25

Cytomegalovirus prophylaxis with letermovir in pediatric (birth ... At exposures achieved, letermovir was efficacious and safe in preventing clinically significant CMV infection in pediatric allogeneic HCT ...