Valganciclovir for Cytomegalovirus Infection

(KPoP Trial)

Recruiting at 4 trial locations

Overseen By Megan Gish

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, San Francisco

Must not be taking: Immunoglobulins, Belatacept, Alemtuzumab, Rituximab

Disqualifiers: Breastfeeding, Allergy to drugs, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 200 days

360 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking immunoglobulin or CMV-specific immunoglobulin, you must not have received it within the last 3 months to participate.

Is valganciclovir safe for humans?

Valganciclovir is generally considered safe, but it can cause side effects like neutropenia (a low level of white blood cells) and may affect kidney function with long-term use. ^{1 2 3 4 5}

How does the drug valganciclovir differ from other treatments for cytomegalovirus infection?

Valganciclovir is unique because it can be taken orally, allowing for outpatient treatment, which is more convenient and cost-effective compared to the standard intravenous ganciclovir. It is a prodrug of ganciclovir, meaning it converts into the active drug in the body, and has high bioavailability, making it effective for treating cytomegalovirus infections in transplant patients. ^{1 3 6 7 8}

What is the purpose of this trial?

This is a prospective, randomized multicenter trial of preemptive therapy (PET) vs. antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in adult D+R- kidney transplant recipients (KTR). Patients meeting study eligibility criteria and who have provided informed consent will be randomized (1:1) within 7 days of transplant to receive, in an open label design, either AP with valganciclovir 900 mg orally once daily or letermovir 480 mg orally once daily \[both dose adjusted per Food and Drug Administration (FDA) label\] for 200 days post-transplant), or PET (central lab weekly plasma polymerase chain reaction (PCR) monitoring for CMV deoxyribonucleic acidemia (DNAemia)) for 100 days post-transplant, with oral valganciclovir 900mg orally twice daily (or renally dosed per FDA label) at onset of CMV DNAemia at any level and continued until plasma CMV DNAemia is negative or below the level of quantitation in two consecutive weekly plasma samples. Study participants will be followed for pre-specified outcomes (clinical, laboratory, immunologic, safety) until withdrawal, death, or study closure, up to a maximum of 5.5 years post-transplant. Approximately 360 participants (180 participants in each group) will be randomized into the study. Estimated Time to Complete Enrollment: 4 years

Research Team

Abhijit P. Limaye, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adult kidney transplant recipients who have received an organ from a donor with CMV but do not themselves have CMV. Participants must consent and be able to start the treatment within 7 days of their transplant.

Inclusion Criteria

I received a kidney transplant from a CMV positive donor within the last week.

Subject or legally authorized representative has provided written informed consent

I have never tested positive for CMV and recent tests confirm this.

Exclusion Criteria

Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant

In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)

I have had an organ transplant or multiple organ transplants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive either antiviral prophylaxis with valganciclovir or preemptive therapy with valganciclovir based on CMV DNAemia monitoring

200 days

Follow-up

Participants are monitored for pre-specified outcomes including clinical, laboratory, immunologic, and safety until study closure

up to 5.5 years

Treatment Details

Interventions

• Valganciclovir

Trial Overview The study compares two methods to prevent CMV disease: one group receives antiviral prophylaxis with valganciclovir or letermovir daily for 200 days, while the other gets preemptive therapy, taking valganciclovir only if CMV DNA appears in blood tests for up to 100 days post-transplant.

Participant Groups

Group I: Pre-emptive Therapy Experimental Treatment 1 Intervention

900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.

Group II: Prophylaxis Active Control 1 Intervention

900 mg of Valganciclovir given orally once daily to subjects for 200 days post transplantation. All dosages adjusted for renal dysfunction.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

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 67 solid organ transplant recipients undergoing CMV preemptive therapy, severe neutropenia occurred in 21.8% of patients, but it did not increase the risk of infections, suggesting that neutropenia may not have significant clinical consequences in this context.

Liver transplant recipients were found to be 6.7 times more likely to experience neutropenia compared to kidney transplant recipients, indicating that certain patient groups may require closer monitoring during antiviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. Martín-Gandul, C., Pérez-Romero, P., González-Roncero, FM., et al.[2018]

In a study of 19 patients who underwent allogeneic hematopoietic stem cell transplantation, valganciclovir demonstrated a high efficacy rate of 94.7% in treating cytomegalovirus (CMV) viremia, with many patients showing negative CMV-DNA results within 7 to 14 days of treatment.

The treatment was found to be safe, as no severe adverse effects were reported and there were no occurrences of CMV-related disease, making valganciclovir a promising option for managing CMV viremia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Valganciclovir for treatment of cytomegalovirus viremia in patients following allogeneic hematopoietic stem cell transplantation]. Wang, Y., Huang, XJ., Xu, LP., et al.[2018]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Clinical impact of neutropenia related with the preemptive therapy of CMV infection in solid organ transplant recipients. [2018]

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

High efficacy and low toxicity of short-course oral valganciclovir as pre-emptive therapy for hematopoietic stem cell transplant cytomegalovirus infection. [2019]

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

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Valganciclovir for treatment of cytomegalovirus viremia in patients following allogeneic hematopoietic stem cell transplantation]. [2018]

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

A prospective assessment of valganciclovir for the treatment of cytomegalovirus infection and disease in transplant recipients. [2018]

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

Efficacy of valganciclovir in the treatment of cytomegalovirus disease in kidney and pancreas transplant recipients. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients. [2019]