A Study for Kidney Transplant Recipients at High-Risk of Cytomegalovirus Infection

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of NPC-21 for Kidney Transplant Recipients at High-Risk of Cytomegalovirus Infection

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Disease
• Intervention / Treatment: Drug: NPC-21 Low dose; Drug: NPC-21 High dose; Drug: NPC-21 Placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagakute, Aichi, Japan
      • Research site_204
    • Nagoya, Aichi, Japan
      • Research site_201
    • Toyoake, Aichi, Japan
      • Research site_202
  • Hyogo
    • Kobe, Hyogo, Japan
      • Research site_206
    • Nishinomiya, Hyogo, Japan
      • Research site_205
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan
      • Research site_217
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan
      • Research site_212
  • Okinawa
    • Tomigusuku-shi, Okinawa, Japan
      • Research site_215
  • Osaka
    • Osaka-shi, Osaka, Japan
      • Research site_211
    • Osaka-shi, Osaka, Japan
      • Research site_214
    • Osaka-shi, Osaka, Japan
      • Research site_216
    • Suita, Osaka, Japan
      • Research site_208
  • Tochigi
    • Shimotsuke, Tochigi, Japan
      • Research site_203
  • Tokyo
    • Hachioji-shi, Tokyo, Japan
      • Research site_213
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Scottsdale
  • California
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48084
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati College of Medicine
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Dallas, Texas, United States, 75235
      • Renal Disease Research Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: NPC-21 Placebo; Placebo (normal saline) will be administered	Drug: NPC-21 Placebo; Placebo will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12
Experimental: NPC-21 Low dose; NPC-21 (6mg/kg) will be administered	Drug: NPC-21 Low dose; NPC-21 will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12
Experimental: NPC-21 High dose; NPC-21 (12mg/kg) will be administered	Drug: NPC-21 High dose; NPC-21 will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CMV Disease or CMV Viremia	The proportion of patients with CMV disease (CMV syndrome or tissue-invasive CMV disease) or CMV viremia (defined as the detection of 250 IU/mL in plasma measured by PCR analysis in central laboratory or meets the local criteria for CMV viremia measured by PCR analysis or antigenemia testing) per total patients through 16 weeks from first study drug administration. The non-responders include all patients who develop CMV disease or CMV viremia and patients who discontinue from the study in the absence of CMV disease or CMV viremia.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CMV Disease or CMV Viremia	The proportion of patients with CMV disease or CMV viremia. The non-responders include all patients who develop CMV disease or CMV viremia and patients who discontinue from the study in the absence of CMV disease or CMV viremia.	28 weeks
Incidence of CMV Disease	The proportion of patients with CMV disease	28 weeks
Incidence of CMV Viremia	The proportion of patients with CMV viremia.	28 weeks
Time to Detectable CMV Disease or CMV Viremia	The count and proportion of patients experiencing event and censored will be summarized by treatment group.	28 weeks
Time to Detectable CMV Disease	The count and proportion of patients experiencing event and censored will be summarized by treatment group.	28 weeks
Time to Detectable CMV Viremia	The count and proportion of patients experiencing event and censored will be summarized by treatment group.	28 weeks

Collaborators and Investigators

• Sponsor: Nobelpharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): June 17, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: NPC-21-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No