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

Trial Summary

What is the purpose of this trial?

This is a research study to test the tolerability and clinical effectiveness of the study drug, Letermovir (LET), when used as secondary prophylaxis following treatment of Cytomegalovirus (CMV) infection and disease in a solid organ transplant recipient. This study is an open label trial in which Letermovir will be prescribed to prevent the recurrence of CMV infection and disease in a solid organ transplant recipient following treatment of CMV infection or disease.

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 data supports the effectiveness of the drug Letermovir for solid organ transplant infection?

Letermovir has been shown to be effective in preventing and treating cytomegalovirus (CMV) infections in patients who have undergone various types of transplants, including heart and small bowel transplants, especially when other treatments were not effective due to resistance or side effects. ^{1 2 3 4 5}

How is the drug letermovir different from other treatments for solid organ transplant infections?

Letermovir is unique because it is a novel antiviral drug that targets the cytomegalovirus (CMV) DNA terminase complex, unlike traditional treatments that inhibit CMV DNA polymerase. It is particularly useful for patients with ganciclovir-resistant CMV infections and is well-tolerated, offering an alternative when other drugs cause severe side effects or resistance. ^{2 3 4 5 6}

Research Team

Jennifer Chow, M.D.

Principal Investigator

Tufts Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 (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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of the anti-human cytomegalovirus drug letermovir in subjects with hepatic impairment. [2021]

2. United States 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Letermovir: First Global Approval. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Letermovir use to treat complex cytomegalovirus reactivations in two heart transplant recipients. [2022]

5. United States 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. [2021]

6. Denmark pubmed.ncbi.nlm.nih.gov

Letermovir treatment for CMV infection in kidney and pancreas transplantation: A valuable option for complicated cases. [2022]