Letermovir for Solid Organ Transplant Infection

Overseen By Whitney K Perry, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Tufts Medical Center

Disqualifiers: Renal insufficiency, Hepatic insufficiency, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Letermovir, a medication designed to prevent Cytomegalovirus (CMV) from recurring in individuals who have undergone a solid organ transplant, such as a heart, kidney, or liver. Researchers aim to evaluate Letermovir's effectiveness and tolerability when used after treating a CMV infection. Suitable candidates have recently received treatment for CMV disease following a transplant and require additional medication to prevent recurrence. As a Phase 4 trial, Letermovir has already received FDA approval and demonstrated effectiveness, and this research seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for Letermovir?

Research has shown that Letermovir is generally safe and well-tolerated for preventing Cytomegalovirus (CMV) in organ transplant recipients. In several studies, most patients continued using Letermovir without major issues. Specifically, one study found that 92.3% of patients completed their Letermovir treatment after a heart transplant without significant problems.

Letermovir is also approved for preventing CMV in other types of transplants, such as bone marrow transplants, and tends to be less toxic than other treatments. This approval reflects its good safety record. In real-world use, Letermovir has proven effective and safe, particularly for high-risk kidney transplant patients.

Overall, the evidence suggests that Letermovir is a safe option for preventing CMV in organ transplant recipients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Letermovir is unique because it offers a new approach to preventing infections in solid organ transplant patients by specifically targeting the cytomegalovirus (CMV). Unlike standard antiviral treatments, which can have significant side effects and are often used reactively once an infection has occurred, Letermovir is designed to be used prophylactically, meaning it helps to prevent infections before they start. Researchers are excited about Letermovir because it has a different mechanism of action, inhibiting the CMV terminase complex, which could reduce the risk of CMV reactivation without the toxicity associated with other antiviral drugs. This potential for fewer side effects and a preventive strategy makes Letermovir a promising option for improving the quality of life and outcomes for transplant recipients.

What is the effectiveness track record for Letermovir in preventing CMV infection recurrence in solid organ transplant recipients?

Research has shown that Letermovir helps prevent Cytomegalovirus (CMV) infections in organ transplant recipients. One study found that Letermovir reduced CMV infections in these patients. In kidney transplant patients, Letermovir performed as well as other treatments, such as valganciclovir, in preventing CMV disease. Another study found that 92.3% of heart transplant patients completed their Letermovir treatment without issues, demonstrating its safety and effectiveness. Overall, Letermovir has consistently delivered good results in managing CMV risk for organ transplant recipients. Participants in this trial will receive Letermovir in a single-arm study to further evaluate its effectiveness and safety. ^{1 2 5 6 7}

Who Is on the Research Team?

Jennifer Chow, M.D.

Principal Investigator

Tufts Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a solid organ transplant (heart, kidney, or liver) and are recovering from treated CMV disease. They should need secondary prophylaxis against CMV and be able to follow up for 6 months. Excluded are those with very low kidney function, severe liver issues, recent malignancies other than certain skin cancers, pregnant or breastfeeding individuals, drug abusers within the last 6 months, or participants in conflicting trials.

Inclusion Criteria

Patient able to participate with follow-up for 6 months

Not enrolled in competing clinical trials

I am an adult organ transplant recipient needing further treatment for CMV.

Exclusion Criteria

My liver is not working well (severe issues).

I am on dialysis.

Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Secondary Prophylaxis

Participants receive Letermovir 480 mg orally once a day for 60 days to prevent recurrence of CMV infection and disease

8 weeks

2 visits (in-person) for T cell assays

Follow-up

Participants are monitored for safety and effectiveness after discontinuation of secondary prophylaxis

4 months

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• Letermovir

Trial Overview The study tests Letermovir as a preventive treatment to stop Cytomegalovirus (CMV) from coming back in patients who have received an organ transplant and already been treated for CMV infection. It's an open-label trial where everyone knows they're getting Letermovir.

How Is the Trial Designed?

Group I: single arm Experimental Treatment 1 Intervention

This is an open label single arm study

Who Is Running the Clinical Trial?

Tufts Medical Center

Lead Sponsor

Trials

264

Recruited

264,000+

Published Research Related to This Trial

Letermovir, an anti-CMV drug, was successfully used to treat ganciclovir-resistant CMV colitis in a heart transplant recipient, demonstrating its potential as a curative option.

In a second case, while letermovir was used as pre-emptive therapy for CMV reactivation, it did not prevent CMV esophagitis, indicating that while effective for secondary prophylaxis, it may not always prevent all forms of CMV-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir use to treat complex cytomegalovirus reactivations in two heart transplant recipients. Boignard, A., Augier, C., Kheng, M., et al.[2022]

In a Phase 1 trial involving 33 female subjects, letermovir showed increased exposure in individuals with hepatic impairment, with a 1.37-fold increase in moderate impairment and a 2.34-fold increase in severe impairment compared to healthy controls.

Despite the increased exposure, letermovir (60 mg for moderate and 30 mg for severe impairment) was generally well-tolerated, indicating its potential safety for use in patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of the anti-human cytomegalovirus drug letermovir in subjects with hepatic impairment. Kropeit, D., McCormick, D., Erb-Zohar, K., et al.[2021]

Letermovir (Prevymis™) is an effective prophylactic treatment for preventing cytomegalovirus (CMV) infection and disease in adult patients who are CMV-seropositive and have received an allogeneic hematopoietic stem cell transplant, with approvals in Canada and the USA.

The drug works by inhibiting the CMV DNA terminase complex and has received positive regulatory feedback in Europe, indicating its potential for broader international use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir: First Global Approval. Kim, ES.[2019]

Letermovir was effective in achieving viral clearance in four transplant patients with refractory or ganciclovir-resistant CMV infection, demonstrating its potential as a valuable treatment option in this challenging context.

The treatment was well tolerated, with resolution of leukopenia, although adjustments to immunosuppressive therapy were necessary, highlighting the need for careful management to prevent acute rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir treatment for CMV infection in kidney and pancreas transplantation: A valuable option for complicated cases. Ortiz, F., Lempinen, M., Aaltonen, S., et al.[2022]

Letermovir, a novel antiviral agent, was successfully used to treat CMV disease in a small bowel transplant patient who had ganciclovir resistance and severe intolerance to foscarnet, marking its first reported use in this context.

This case highlights the potential of letermovir as an alternative treatment option for CMV in solid organ transplant patients, especially when traditional therapies are ineffective or poorly tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Successful Use of Twice-Daily Letermovir in the Treatment of Resistant Cytomegalovirus in a Small Bowel Transplant Recipient. Joharji, H., Alaidaros, F., Koujan, H., et al.[2022]

Letermovir, an antiviral agent typically used for preventing CMV infection in stem cell transplant recipients, was successfully used off-label to treat a patient with resistant CMV disease after renal transplant.

This case report is significant as it demonstrates the effectiveness of combining letermovir with hyperimmune CMV immunoglobulin for treating high viral load CMV infections, providing a potential alternative when standard treatments are inadequate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Viremia in a Renal Transplant Recipient With Letermovir and Adjunct Hyperimmune Cytomegalovirus Immunoglobulin: A Case Report. Pearston, AP., Ingemi, AI., Ripley, K., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41137659/

Letermovir Conversion for Cytomegalovirus Prophylaxis in ... LTV was effective and well-tolerated for primary CMV prophylaxis in an extra-renal transplant population and may be a safe alternative in patients ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33469975/

Letermovir prophylaxis in solid organ transplant-Assessing ... The primary outcome was the rate of CMV breakthrough infections while on prophylaxis. Secondary outcomes included rate of leukopenia, doses of immunosuppression ...

3. merck.com merck.com/news/mercks-prevymis-demonstrates-efficacy-in-phase-3-study-for-prevention-of-cytomegalovirus-disease-in-adults-after-kidney-transplantation/

Merck's PREVYMIS™ Demonstrates Efficacy in Phase 3 ... At 52 weeks following kidney transplant, trial results met the primary endpoint demonstrating that PREVYMIS was effective and non-inferior to valganciclovir ...

4. merckconnect.com merckconnect.com/prevymis/kidney-transplant-endpoint-results/

Study results in adult kidney transplant patients Review the primary and exploratory endpoint results from a clinical trial studying the efficacy of PREVYMIS® (letermovir) in adult kidney transplant recipients.

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

Efficacy of Letermovir for Cytomegalovirus Prophylaxis in ... Most patients, 92.3%, were able to complete letermovir therapy for CMV prophylaxis post–heart transplantation. ABSTRACT. Background.

6. academic.oup.com academic.oup.com/ofid/article/doi/10.1093/ofid/ofae631.2512/7987773

P-2361. Real-World Experience of Letermovir for CMV ... In 2023, letermovir was approved for CMV prophylaxis in high-risk kidney transplant recipients. The aim of this study was to describe our real- ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2805945

Letermovir vs Valganciclovir for Prophylaxis of ... This randomized clinical trial compares the efficacy and safety of letermovir vs valganciclovir prophylaxis for cytomegalovirus (CMV) ...