CMV Immunity Monitoring for Lung Transplant Complications

Overseen By Tyler Lewis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Valganciclovir

Disqualifiers: Pregnancy, Breastfeeding, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 12 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety and feasibility of using a laboratory test to guide duration of antiviral prophylaxis with valganciclovir (medication used to prevent viral infections) after lung transplant. The laboratory test, inSIGHT™ CMV T Cell Immunity Panel, measures patients' immune response to a common viral infection known as cytomegalovirus (CMV). The goal of this study will be to safely decrease how long patients need to take valganciclovir based on the results of the CMV T Cell Immunity Panel.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It focuses on monitoring and adjusting the duration of valganciclovir (a medication to prevent viral infections) after a lung transplant.

What data supports the effectiveness of the drug valganciclovir for preventing CMV complications in lung transplant patients?

Research shows that valganciclovir is effective in preventing CMV infections in lung transplant patients, with significantly lower CMV disease rates compared to those who received acyclovir. Additionally, it does not impair the development of CMV-specific immunity, which is important for long-term health. ^{1 2 3 4 5}

Is valganciclovir safe for humans?

Valganciclovir is generally considered safe for humans, but it can cause some side effects like neutropenia (a low level of white blood cells) and hematological toxicity (blood-related side effects). It is used to prevent cytomegalovirus (CMV) infections in transplant patients and has a similar safety profile to oral ganciclovir, though with a slightly higher risk of neutropenia. ^{2 6 7 8 9}

How does the drug valganciclovir differ from other treatments for CMV in lung transplant patients?

Valganciclovir is unique because it can be used as a long-term prophylactic (preventive) treatment without impairing the development of CMV-specific immunity in lung transplant patients, unlike some other antiviral treatments that might delay immune response development. ^{3 4 8 10 11}

Research Team

Luis Angel, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals who have had a lung transplant at NYU Langone Health, possess immunity to CMV (R+), and can consent to participate. It's not open to those who received anti-thymocyte globulin, underwent perioperative desensitization, or are pregnant/breastfeeding.

Inclusion Criteria

I had a lung or multi-organ transplant at NYU Langone Health.

Able and willing to provide informed consent

Pre-existing serological immunity to CMV (R+)

Exclusion Criteria

I have undergone treatment to reduce my body's reaction to surgery.

I am receiving anti-thymocyte globulin for immune suppression.

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive antiviral prophylaxis with valganciclovir, guided by the inSIGHT™ CMV T Cell Immunity Panel

Up to 12 months

CMV-TCIP measured every 3 months post-transplant

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of CMV and other infections

Up to 12 months

Treatment Details

Interventions

• Cytomegalovirus T Cell Immunity Panel (CMV-TCIP)
• Donor-Derived Cell-Free DNA (dd-cfDNA) Assay
• Valganciclovir

Trial Overview The study tests if monitoring the immune response to cytomegalovirus (CMV) using the inSIGHT™ CMV T Cell Immunity Panel can guide how long patients take valganciclovir after a lung transplant, potentially reducing treatment duration.

Participant Groups

Group I: Lung Transplant Recipients Experimental Treatment 3 Interventions

Lung transplant recipients with pre-transplant serological immunity to CMV. CMV-TCIP will be measured every 3 months post-transplant with antiviral prophylaxis discontinued when threshold is exceeded.

Valganciclovir is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Valcyte for:

• Cytomegalovirus (CMV) retinitis
• Prevention of CMV disease in organ transplant recipients

Approved in United States as Valcyte for:

• Cytomegalovirus (CMV) retinitis
• Prevention of CMV disease in organ transplant recipients

Approved in Canada as Valcyte for:

• Cytomegalovirus (CMV) retinitis
• Prevention of CMV disease in organ transplant recipients

Approved in Japan as Valcyte for:

• Cytomegalovirus (CMV) retinitis
• Prevention of CMV disease in organ transplant recipients

Approved in Switzerland as Valcyte for:

• Cytomegalovirus (CMV) retinitis
• Prevention of CMV disease in organ transplant recipients

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Viracor Eurofins

Collaborator

Trials

1

Recruited

50+

Findings from Research

A 30-year-old lung transplant patient with recurrent CMV retinitis was successfully treated with valganciclovir as maintenance therapy after initial treatment with intravenous ganciclovir.

After 6 months of valganciclovir treatment, the patient showed no active CMV retinitis and maintained excellent vision (20/20) in both eyes, suggesting that valganciclovir is an effective option for preventing CMV retinitis recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valgancyclovir as maintenance therapy for cytomegalovirus retinitis in a lung transplant patient--a case report. Wang, TJ., Lin, CP., Yang, CM., et al.[2018]

In a study of 90 lung transplant recipients, valganciclovir was found to be significantly more effective than acyclovir in preventing cytomegalovirus (CMV) disease, with only 2.2% of patients developing CMV disease compared to 20% in the acyclovir group.

Prophylaxis with valganciclovir for at least 180 days resulted in a higher rate of freedom from CMV infection and disease (90% to 95%) compared to shorter durations, indicating that longer treatment is crucial for effective prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. Zamora, MR., Nicolls, MR., Hodges, TN., et al.[2023]

In a study involving 19 lung transplant patients, pre-emptive treatment with oral valganciclovir effectively reduced cytomegalovirus (CMV) levels, with all patients achieving undetectable viral loads after an average of 22 days of treatment.

The treatment was generally safe, with mild to moderate leucopenia occurring in 36.8% of patients, but no serious drug-related complications were reported, highlighting the need for regular blood monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation. Aigner, C., Jaksch, P., Winkler, G., et al.[2018]

A pilot study found that lung transplant recipients on valganciclovir prophylaxis for a median of 6 months still developed detectable CMV-specific immunity, indicating that the antiviral treatment does not hinder the immune response to CMV.

The study showed that the CMV-specific T cell responses in patients on valganciclovir were comparable to those in seropositive recipients not on antiviral medications, suggesting that long-term prophylaxis may be safe regarding immune development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis. Snyder, LD., Medinas, R., Chan, C., et al.[2023]

In a pilot study involving 37 patients undergoing allogeneic hematopoietic stem cell transplant, valganciclovir (VGV) demonstrated similar efficacy to ganciclovir (GCV) for clearing cytomegalovirus (CMV) viremia, with clearance rates of 89.5% for VGV and 83% for GCV within 28 days.

Both treatments had comparable toxicity profiles, and importantly, no patients developed CMV disease during the trial, indicating that VGV is a safe and effective alternative to GCV for pre-emptive therapy in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04-0274) and review of the literature. Chawla, JS., Ghobadi, A., Mosley, J., et al.[2018]

In a study of 13 adult patients who experienced relapses of cytomegalovirus (CMV) infection after initial treatment, only one patient developed drug-resistant strains after receiving intravenous ganciclovir, indicating a low rate of drug resistance (3.8% overall).

No drug resistance was found in patients treated with valganciclovir, confirming its safety and efficacy as a pre-emptive therapy for CMV in hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus. Allice, T., Busca, A., Locatelli, F., et al.[2018]

In a study of 24 lung transplant patients, higher trough concentrations of ganciclovir were linked to an increased risk of severe leukopenia (grade 3 or higher), with a critical cutoff identified at 872.0 ng/mL.

Factors such as reduced creatinine clearance and lung re-transplantation significantly influenced the pharmacokinetics of ganciclovir, indicating that these patients may require closer monitoring to prevent hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trough ganciclovir concentration as predictor of leukopenia in lung transplant recipients receiving valganciclovir prophylaxis. Katada, Y., Nakagawa, S., Nagao, M., et al.[2023]

Valganciclovir prophylaxis in lung transplant recipients resulted in a lower incidence of CMV disease (7.9%) compared to oral ganciclovir (16.1%), indicating it may be more effective for preventing CMV-related complications.

While valganciclovir was associated with a higher incidence of leukopenia and treatment withdrawal due to adverse effects, it is still considered safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients. Monforte, V., Lopez, C., Santos, F., et al.[2023]

In a study of 364 high-risk solid organ transplant recipients, once-daily oral valganciclovir was found to be as effective as oral ganciclovir taken three times a day in preventing cytomegalovirus (CMV) disease, with similar overall safety profiles.

Valganciclovir resulted in significantly lower rates of CMV viremia during prophylaxis and delayed the onset of CMV disease compared to ganciclovir, although it was associated with a higher incidence of neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Paya, C., Humar, A., Dominguez, E., et al.[2023]

In a study of 128 lung transplant recipients, indefinite prophylaxis with valganciclovir resulted in a low incidence of cytomegalovirus (CMV) disease (4.7%) and a low rate of drug resistance (2.3%).

Discontinuation of valganciclovir prophylaxis was associated with a significantly higher incidence of laboratory-detected CMV infection (40.7% vs. 12.7%), indicating the importance of continued prophylaxis to prevent infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis. Wiita, AP., Roubinian, N., Khan, Y., et al.[2022]

In a study of 32 lung transplant recipients, two CMV immunity assays (QuantiFERON-CMV and T-Track-CMV) were found to predict the risk of CMV replication in the blood, with negative results indicating a higher likelihood of viremia.

While the assays showed some concordance in predicting blood CMV replication, they were not effective in predicting CMV replication in the lung allograft, suggesting that circulating CMV-specific T-cell immunity does not correlate with control of infection in the transplanted lung.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus Immunity Assays Predict Viremia but not Replication Within the Lung Allograft. Li, J., Gardiner, BJ., Stankovic, S., et al.[2023]

References

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

Valgancyclovir as maintenance therapy for cytomegalovirus retinitis in a lung transplant patient--a case report. [2018]

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

Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation. [2023]

3. Austria pubmed.ncbi.nlm.nih.gov

Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation. [2018]

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

Polyfunctional cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis. [2023]

5. Denmark pubmed.ncbi.nlm.nih.gov

Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04-0274) and review of the literature. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus. [2018]

7. Denmark pubmed.ncbi.nlm.nih.gov

Trough ganciclovir concentration as predictor of leukopenia in lung transplant recipients receiving valganciclovir prophylaxis. [2023]

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

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients. [2023]

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

Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. [2023]

10. Denmark pubmed.ncbi.nlm.nih.gov

Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis. [2022]

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

Cytomegalovirus Immunity Assays Predict Viremia but not Replication Within the Lung Allograft. [2023]