Clinical trial NCT06798909: Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients
Official title: Kidney Transplant Preemptive Therapy or Prophylaxis (KPoP) for CMV Prevention in D+R- Recipients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Cytomegalovirus (CMV)
Kidney Transplant; Complications
Kidney Diseases
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2025-01-29
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

1. Subject or legally authorized representative has provided written informed consent.
2. Age ≥ 18 years of age at the time of informed consent.
3. Negative for antibody to CMV as assessed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory between 28 days prior to transplant and 7 days post-transplant, but prior to enrollment, and no history of positive CMV serology Immunoglobulin G (IgG) antibody
4. Received a first kidney transplant from a CMV seropositive donor in the past 7 days prior to enrollment
5. Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (standard of care (SOC) results within 7 days prior to transplant may be used), and must also agree to use a medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence from the time of enrollment through 1 month after discontinuation of either PET or AP.

   NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy).
6. If male, and not surgically sterile, must agree to practice barrier method of contraception or abstinence from the time of enrollment through 1 month after discontinuation of either PET or AP.

Exclusion Criteria:

1. In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
2. Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
3. Allergy to valganciclovir/ganciclovir or Letermovir
4. Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
5. Currently enrolled in another interventional study that, in the investigator's opinion, could affect evaluation of the safety and/or efficacy outcomes
6. Most recent platelet count post-transplant \<25,000/uL
7. Most recent ANC performed post-transplant \<1000/uL
8. Multi-organ transplant or have undergone prior organ transplant
9. Baseline immunodeficiency prior to transplant:

   1. Known or suspected human immunodeficiency virus (HIV) infection
   2. Congenital or acquired immunodeficiency
10. Unacceptable immunosuppression

    1. Receipt of desensitization therapy prior to kidney transplant, or
    2. Receipt of a blood type A, B, or O-incompatible kidney transplant, or
    3. Receipt or planned receipt of any of the following: belatacept, alemtuzumab, or rituximab

Primary outcomes:
measure: Incidence of endpoint committee (EC)-confirmed CMV disease (either syndrome or end-organ) by 1-year post-transplant.
timeFrame: Within 1-year post-transplant
Secondary outcomes:
measure: Non-inferiority of PET (within a 10% margin) vs AP for EC-confirmed CMV disease by 1-year post-transplant, contingent on failure to meet the primary superiority endpoint.
timeFrame: by 1-year post-transplant
measure: Proportion of participants with investigator-determined CMV disease
timeFrame: by 1-year post transplant
measure: Time in days to biopsy-proven acute rejection (BIPAR)
timeFrame: From date of randomization until the date of BIPAR from any cause, assessed up to 5.5 years
measure: Time in days to graft loss
timeFrame: From date of randomization until the date of graft loss from any cause, assessed up to 5.5 years
measure: Time in days to death
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5.5 years
measure: Mean estimated glomerular filtration rate (eGFR) in mL/min/1.73m2 at 1, 2, 3, and 4-years post-transplant
timeFrame: 1, 2, 3, and 4-years post-transplant
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco School of Medicine
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Livingston
country: United States
facility: Robert Wood Johnson Health Network Barnabas Health
state: New Jersey
city: Richmond
country: United States
facility: Medical College of Virginia Commonwealth
state: Virginia
Study officials:
affiliation: University of California, San Francisco
name: Abhijit P. Limaye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Limaye AP, Budde K, Humar A, Vincenti F, Kuypers DRJ, Carroll RP, Stauffer N, Murata Y, Strizki JM, Teal VL, Gilbert CL, Haber BA. Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial. JAMA. 2023 Jul 3;330(1):33-42. doi: 10.1001/jama.2023.9106.
citation: Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.