Clinical trial NCT04225923: A Study for Kidney Transplant Recipients at High-Risk of Cytomegalovirus Infection
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of NPC-21 for Kidney Transplant Recipients at High-Risk of Cytomegalovirus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus Disease
Lead sponsor: Nobelpharma
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective is to assess the efficacy and safety of NPC-21 when administered prophylactically to cytomegalovirus (CMV) seronegative patients receiving a first kidney transplant from a CMV seropositive donor.

Detailed description: This is a Phase 2, randomized, double-blind, placebo-controlled study of NPC-21 for kidney transplant recipients at high risk of CMV infection in the United States and Japan. Approximately 108 eligible patients will be randomized prior to first study drug administration to receive low-dose NPC 21, high-dose NPC-21, or placebo. Randomization will be stratified by region (United States or Japan)

Eligibility criteria: Inclusion Criteria:

1. Male or female patients 18 to 75 years of age in the United States or 20 to 75 years of age in Japan at the time of obtaining informed consent.
2. Patients must be CMV seronegative pre-transplant and scheduled to receive or have received (within 7 days prior to first study drug administration) a first kidney transplant from a CMV seropositive donor.
3. Patients must be willing and able to give written informed consent for participation in the study.
4. Patients must be eligible to undergo kidney transplantation from a living or deceased donor, as per institutional standards.
5. Patients must agree with contraception by using appropriate contraceptive measures.

Exclusion Criteria:

1. Patients who have received a previous solid organ transplantation or hematopoietic stem cell transplantation.
2. Patients who receive a multi-organ transplant.
3. Patients who have CMV disease or CMV viremia at Screening.
4. Patients who have a positive donor-specific antibody within 90 days prior to Randomization confirmed via medical records.
5. Patients whose body weight is more than 120 kg at Screening.
6. Patients who have received the following anti-CMV therapy within 7 days prior to Randomization and/or plan to receive the following anti-CMV therapy during the study:

   ・ Anti-CMV agents (eg, foscarnet, ganciclovir, valganciclovir, letermovir, high dose acyclovir, high dose valacyclovir, high dose famciclovir, or cidofovir).

   Note: The use of anti-CMV agents per local standard of care during the Rescue Phase of the study is permitted.

   Note: The use of anti-herpes simplex virus and anti-varicella zoster virus prophylaxis for at-risk patients is recommended (as long as the doses are below the one specified above).
7. Patients who have received the following therapy within 28 days prior to Randomization and/or plan to receive the following anti-CMV therapy during the study:

   * CMV hyperimmune globulin (eg, CytoGam).
   * Intravenous immunoglobulin.
   * Plasmapheresis (receipt prior to first study drug administration is acceptable).
8. Patients with a history of a serious drug allergy to proteins, immunoglobulins, transfusions, or vaccines or any excipient of the NPC-21 formulation.
9. Patients with severe hepatic insufficiency at Screening (eg, Child-Pugh Class C).
10. Patients with active and untreated hepatitis B virus or hepatitis C virus, as documented as part of the pre-transplant screening.
11. Patients with known human immunodeficiency virus infection, based on medical records serology.
12. Patients with any uncontrolled infection at Randomization or a history of serious and uncontrolled infection within 6 months prior to Randomization.
13. Patients who are pregnant or lactating.
14. Patients with a history of malignancy within 5 years prior to Randomization other than curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma.
15. Patients with a history of alcohol or drug abuse or dependence within 1 year prior to Randomization that, in the opinion of the Investigator, would preclude study participation.
16. Patients who have previously participated in this study or any other study involving NPC-21.
17. Patients who have previously participated or are currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent.
18. Patients who have participated in another interventional clinical study and received another investigational product (ie, not approved by the Food and Drug Administration in the United States or the Ministry of Health, Labour and Welfare in Japan) within 90 days before Randomization.
19. Patients who are unable or unwilling, in the opinion of the Investigator, to comply with the protocol.

Primary outcomes:
measure: Incidence of CMV Disease or CMV Viremia
timeFrame: 16 weeks
Secondary outcomes:
measure: Incidence of CMV Disease or CMV Viremia
timeFrame: 28 weeks
measure: Incidence of CMV Disease
timeFrame: 28 weeks
measure: Incidence of CMV Viremia
timeFrame: 28 weeks
measure: Time to Detectable CMV Disease or CMV Viremia
timeFrame: 28 weeks
measure: Time to Detectable CMV Disease
timeFrame: 28 weeks
measure: Time to Detectable CMV Viremia
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: Renal Disease Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Nagakute
country: Japan
facility: Research site_204
state: Aichi
city: Nagoya
country: Japan
facility: Research site_201
state: Aichi
city: Toyoake
country: Japan
facility: Research site_202
state: Aichi
city: Kobe
country: Japan
facility: Research site_206
state: Hyogo
city: Nishinomiya
country: Japan
facility: Research site_205
state: Hyogo
city: Kawasaki-shi
country: Japan
facility: Research site_217
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Research site_212
state: Kumamoto
city: Tomigusuku-shi
country: Japan
facility: Research site_215
state: Okinawa
city: Osaka-shi
country: Japan
facility: Research site_211
state: Osaka
city: Osaka-shi
country: Japan
facility: Research site_214
state: Osaka
city: Osaka-shi
country: Japan
facility: Research site_216
state: Osaka
city: Suita
country: Japan
facility: Research site_208
state: Osaka
city: Shimotsuke
country: Japan
facility: Research site_203
state: Tochigi
city: Hachioji-shi
country: Japan
facility: Research site_213
state: Tokyo
Study officials:
References:
citation: Ichimaru N, Natori Y, Alloway RR, Wojciechowski D, Castillo Almeida NE, Futamura K, Watanabe T, Nakagawa K, Egawa H; LionHeart21 Study Group. Phase 2, Randomized, Double-blind, Placebo-controlled Study of Fiztasovimab (NPC-21) for Kidney Transplant Recipients at High Risk of Cytomegalovirus Infection (LionHeart21). Transplantation. 2025 Jun 1;109(6):985-993. doi: 10.1097/TP.0000000000005260. Epub 2025 May 18.