Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients

NCT06798909 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: STUDY000206951R01AI184205-01
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 5

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

Conditions

Cytomegalovirus (CMV); Kidney Transplant; Complications; Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Incidence of endpoint committee (EC)-confirmed CMV disease (either syndrome or end-organ) by 1-year post-transplant.

  Within 1-year post-transplant

Secondary Outcomes (6)

• 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.

  by 1-year post-transplant

• Proportion of participants with investigator-determined CMV disease

  by 1-year post transplant

• Time in days to biopsy-proven acute rejection (BIPAR)

  From date of randomization until the date of BIPAR from any cause, assessed up to 5.5 years

• Time in days to graft loss

  From date of randomization until the date of graft loss from any cause, assessed up to 5.5 years

• Time in days to death

  From date of randomization until the date of death from any cause, assessed up to 5.5 years

Study Arms (2)

Pre-emptive Therapy

EXPERIMENTAL

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.

Drug: Valganciclovir (Pre-emptive CMV Therapy)

Prophylaxis

ACTIVE COMPARATOR

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

Drug: Valganciclovir CMV Prophylaxis

Interventions

Valganciclovir CMV Prophylaxis DRUG

Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 200 days post transplantation as prophylaxis.

Prophylaxis

Valganciclovir (Pre-emptive CMV Therapy) DRUG

Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.

Pre-emptive Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject or legally authorized representative has provided written informed consent.
• Age ≥ 18 years of age at the time of informed consent.
• Negative for IgG antibody to CMV as assessed in a CLIA-certified laboratory between 28 days prior to transplant and up to 7 days post-transplant but prior to randomization.
• Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 7 days prior to enrollment
• Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (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 until discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.
• 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).
• If male, must agree to practice a barrier method of contraception or abstinence from the time of enrollment through 3 months after discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.

You may not qualify if:

• In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
• Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
• Allergy to valganciclovir/ganciclovir or Letermovir
• Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
• Currently enrolled or anticipated enrollment in another interventional study that, in the opinion of scientific leadership team, could affect evaluation of the primary safety and/or efficacy outcomes.
• Most recent platelet count post-transplant \<25,000/uL
• Most recent ANC performed post-transplant \<1000/uL
• Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days
• Prior or planned receipt of a hematopoietic cell transplant
• Baseline immunodeficiency prior to transplant, including but not limited to:
• Known or suspected HIV infection
• Congenital or acquired immunodeficiency
• Unacceptable immunosuppression
• Receipt of desensitization therapy prior to kidney transplant, or
• Receipt of an ABO-incompatible kidney transplant except A2 to blood type B

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (5)

University of California, San Francisco School of Medicine

San Francisco, California, 94117, United States

RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

RECRUITING

Robert Wood Johnson Health Network Barnabas Health

Livingston, New Jersey, 07039, United States

RECRUITING

Medical College of Virginia Commonwealth

Richmond, Virginia, 23219, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 37279999 BACKGROUND

• 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.

  PMID: 29596116 BACKGROUND

MeSH Terms

Conditions

Kidney Diseases

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Abhijit P. Limaye, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Gish

CONTACT

415-476-1985; megan.gish@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 29, 2025
• Study Start: July 22, 2025
• Primary Completion (Estimated): November 30, 2030
• Study Completion (Estimated): May 31, 2031
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)