Letermovir for CMV in Transplant Recipients

Overseen By Sandesh Parajuli, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Wisconsin, Madison

Must not be taking: CMV vaccine

Disqualifiers: Ganciclovir-resistant CMV, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 12 weeks

90 Participants Needed

Trial Summary

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 CMV in transplant recipients?

Letermovir has been shown to be effective in preventing CMV infection in patients who have received a hematopoietic stem cell transplant. It has also been used successfully in some cases to treat CMV infections that are resistant to other drugs, like ganciclovir, in transplant recipients. ^{1 2 3 4 5}

Is Letermovir safe for use in humans?

Letermovir is generally considered safe for use in humans, with fewer side effects compared to other anti-CMV drugs, especially in patients who have undergone stem cell transplants. ^{1 2 6 7 8}

How is the drug Letermovir unique for treating CMV in transplant recipients?

Letermovir is unique because it is specifically designed to inhibit the CMV DNA terminase complex, making it effective against CMV strains resistant to other treatments like ganciclovir. It is also known for having fewer side effects compared to other CMV drugs, and it can be administered both orally and intravenously. ^{1 2 3 4 6}

What is the purpose of this trial?

This study is designed to assess how effective letermovir is in preventing recurrence of cytomegalovirus (CMV) infection in adult kidney or kidney/pancreas transplant recipients who are UW Health patients. Participants will be in the study for about 6 months.

Research Team

Margaret Jorgenson, PharmD, BCTXP

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adult kidney or kidney/pancreas transplant recipients at UW Health who are at risk of cytomegalovirus (CMV) infection. The study lasts about 6 months, and participants must meet specific health criteria to join.

Inclusion Criteria

I am at high risk for CMV infection after my transplant.

Patient must demonstrate proven or presumptive lack of cell-mediated immunity (CMI), either by CMI testing or risk factor screening

Patient must be able to provide informed consent to participate

Exclusion Criteria

Patient is currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent

Patient is unable or unwilling, in the opinion of the Investigator, to comply with the protocol

I have a CMV infection that did not respond to ganciclovir treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are converted from ganciclovir derivatives to letermovir for secondary prophylaxis of CMV infection

12 weeks

Weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 90 days

Monthly visits

Treatment Details

Interventions

• Letermovir

Trial Overview The effectiveness of Letermovir (Prevymis) in preventing the recurrence of CMV infections post-transplant is being tested. Participants will receive this medication over a period to assess its protective benefits.

Participant Groups

Group I: Letermovir for CMV in Transplant Patients Experimental Treatment 1 Intervention

Enrolled participants will be converted from treatment with ganciclovir derivatives to letermovir

Letermovir is already approved in United States, European Union for the following indications:

Approved in United States as Prevymis for:

• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])
• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])

Approved in European Union as Prevymis for:

• Prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT)
• Prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-])

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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 (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]

In an observational study of 48 transplant recipients treated with Letermovir (LET) for cytomegalovirus (CMV) infection, patients with a viral load below 1000 IU/ml at the start of treatment showed promising virologic outcomes, with only 2 experiencing a significant increase in viral load by week 12.

For patients who started LET with a viral load above 1000 IU/ml, 60% achieved a lower viral load by the end of therapy, indicating that LET may still be beneficial even in cases of higher initial viral loads, although further research is needed to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir treatment of cytomegalovirus infection or disease in solid organ and hematopoietic cell transplant recipients. Linder, KA., Kovacs, C., Mullane, KM., et al.[2021]

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]

In a study of 6 transplant patients treated with letermovir for refractory CMV infection, 3 asymptomatic patients showed a significant decrease in viral load to below 200 IU/mL, indicating potential efficacy of the drug.

No treatment-related adverse effects were reported, suggesting that letermovir may be a safe option for treating CMV infections, although its effectiveness appears to vary and may be enhanced when used alongside other antiviral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir as Salvage Therapy for Cytomegalovirus Infection in Transplant Recipients. Phoompoung, P., Ferreira, VH., Tikkanen, J., et al.[2023]

Letermovir, a new anti-CMV drug with fewer side effects, was successfully used off-label to treat a heart transplant recipient with ganciclovir-resistant CMV colitis, highlighting its potential as an alternative treatment.

The case suggests that monitoring CMV-pp65 antigenemia levels could be a useful additional marker for assessing the efficacy of letermovir treatment, alongside traditional CMV-DNA PCR levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia. Yanase, T., Hatano, M., Bujo, C., et al.[2023]

In a study of 48 CMV-seropositive allogeneic stem cell transplant recipients, letermovir prophylaxis significantly reduced the incidence of CMV reactivation to 33.3% compared to 76.2% in the control group, highlighting its efficacy in preventing this serious complication.

Patients receiving letermovir also showed improved overall survival at 180 days (92.6% vs. 80.9% in the control group), suggesting that prolonged use of letermovir may provide additional survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letermovir Prophylaxis for CMV Reactivation in Allogeneic Stem Cell Recipients: A Retrospective Single Center Analysis. Koch, K., Osswald, L., Miller, I., et al.[2022]

In a 6-year post-marketing surveillance study involving 461 Japanese patients who received allogenic hematopoietic stem-cell transplantation, letermovir was found to be safe, with 13.9% experiencing adverse drug reactions, primarily renal impairment and nausea.

The effectiveness of letermovir for CMV prophylaxis was confirmed, with CMV antigen positivity rates of 21.2% at Week 14 and 37.5% at Week 24 after transplantation, indicating its role in reducing CMV infection risk in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Letermovir in Allogenic Hematopoietic Stem Cell Transplantation Recipients: Interim Report of Post-marketing Surveillance in Japan. Hiraishi, I., Ueno, R., Watanabe, A., et al.[2022]

References

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

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

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

Letermovir: First Global Approval. [2019]

3. Denmark pubmed.ncbi.nlm.nih.gov

Letermovir treatment of cytomegalovirus infection or disease in solid organ and hematopoietic cell transplant recipients. [2021]

4. 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]

5. United States pubmed.ncbi.nlm.nih.gov

Letermovir as Salvage Therapy for Cytomegalovirus Infection in Transplant Recipients. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Letermovir Prophylaxis for CMV Reactivation in Allogeneic Stem Cell Recipients: A Retrospective Single Center Analysis. [2022]

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

Safety and Effectiveness of Letermovir in Allogenic Hematopoietic Stem Cell Transplantation Recipients: Interim Report of Post-marketing Surveillance in Japan. [2022]