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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different strategies to prevent cytomegalovirus (CMV) disease in individuals who have recently received a kidney transplant from a CMV-positive donor. Participants will either take a preventive daily medication (valganciclovir, an antiviral drug) or undergo weekly monitoring for CMV, receiving treatment if the virus appears. The study seeks individuals who have had their first kidney transplant within the past week, have no history of CMV, and received the kidney from a CMV-positive donor. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that valganciclovir is generally safe for transplant patients, though some safety concerns exist. It has proven effective in preventing CMV infections in organ transplant recipients. However, some side effects have been reported, including low white blood cell counts, which can increase infection risk, and other blood-related issues like neutropenia and thrombocytopenia.

Valganciclovir has also treated CMV infections in individuals with weakened immune systems, such as those with AIDS, providing context for its safety. While effective, monitoring for side effects during treatment is important. Prospective trial participants should discuss these potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Valganciclovir for cytomegalovirus (CMV) infection because it offers a targeted approach to managing the virus in transplant patients. Unlike standard antiviral treatments like ganciclovir or foscarnet, Valganciclovir allows for both prophylactic and pre-emptive therapy methods. The prophylaxis arm uses a once-daily oral dose, which simplifies the regimen for patients, while the pre-emptive therapy arm tailors the dosing to the presence of CMV, potentially reducing the risk of unnecessary medication exposure. Additionally, all dosages are adjusted for renal function, making it safer for individuals with compromised kidney function. This versatility and patient-friendly administration are key reasons for the excitement surrounding Valganciclovir.

What evidence suggests that this trial's treatments could be effective for preventing cytomegalovirus disease in kidney transplant recipients?

Studies have shown that valganciclovir effectively prevents cytomegalovirus (CMV) disease in kidney transplant patients. In this trial, participants in the prophylaxis arm will receive valganciclovir as a preventive treatment, significantly lowering the chance of developing CMV disease if taken for 200 days. Alternatively, participants in the pre-emptive therapy arm will begin valganciclovir treatment only after virus detection, which also effectively reduces CMV disease. Some research suggests that pre-emptive therapy might lower the risk of CMV disease over a year compared to preventive treatment. Overall, both methods show promise in managing CMV in at-risk patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Abhijit P. Limaye, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29166336/

Long-term Results After 7 Years of a Randomized Clinical ... The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2764457

Effect of Preemptive Therapy vs Antiviral Prophylaxis on ... The use of preemptive therapy, compared with antiviral prophylaxis, reduced the 12-month incidence of CMV disease.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522196930

The Efficacy and Safety of 200 Days Valganciclovir ... This study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and ...

4. journals.lww.com journals.lww.com/transplantjournal/fulltext/2018/05000/valganciclovir_prophylaxis_versus_preemptive.37.aspx

Valganciclovir Prophylaxis Versus Preemptive Therapy in... The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome in cytomegalovirus (CMV)- ...

5. academic.oup.com academic.oup.com/cid/article/78/3/562/7456345

Treatment for First Cytomegalovirus Infection Post ... Pre-emptive treatment for CMV following HCT is generally effective in preventing CMV tissue-invasive disease (ie, end-organ disease) but is associated with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8501296/

Safety of Valganciclovir 450 mg 3 Times Weekly for ... Valganciclovir 450 mg 3 times weekly was found to have similar rates of leukopenia, neutropenia, thrombocytopenia, and CMV infection in comparison to ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/valganciclovir-oral-route/description/drg-20066642

Valganciclovir (oral route) - Side effects & dosage Valganciclovir is used to treat symptoms of cytomegalovirus (CMV) retinitis, an infection in the eyes of people with acquired immunodeficiency syndrome (AIDS).

8. amjtransplant.org amjtransplant.org/article/S1600-6135(22)19693-0/fulltext

The Efficacy and Safety of 200 Days Valganciclovir ... Six‐month prophylaxis is cost effective in transplant patients at high risk for cytomegalovirus infection.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522074846

Efficacy and Safety of Valganciclovir vs. Oral Ganciclovir for ... Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.

10. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0005512

Valganciclovir for Cytomegalovirus Prevention in Solid Organ ... Valganciclovir shows no superior efficacy and significantly higher risk of absolute neutropenia, CMV late-onset disease, and CMV tissue-invasive disease.