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

Study Overview
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Brief Summary
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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
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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)

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

Conditions
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Cytomegalovirus Disease

Intervention / Treatment
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* Drug: NPC-21 Low dose
* Drug: NPC-21 High dose
* Drug: NPC-21 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Patients must be willing and able to give written informed consent for participation in the study. Patients must be eligible to undergo kidney transplantation from a living or deceased donor, as per institutional standards. Patients must agree with contraception by using appropriate contraceptive measures. Exclusion Criteria: Patients who have received a previous solid organ transplantation or hematopoietic stem cell transplantation. Patients who receive a multi-organ transplant. Patients who have CMV disease or CMV viremia at Screening. Patients who have a positive donor-specific antibody within 90 days prior to Randomization confirmed via medical records. Patients whose body weight is more than 120 kg at Screening. 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). 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). Patients with a history of a serious drug allergy to proteins, immunoglobulins, transfusions, or vaccines or any excipient of the NPC-21 formulation. Patients with severe hepatic insufficiency at Screening (eg, Child-Pugh Class C). Patients with active and untreated hepatitis B virus or hepatitis C virus, as documented as part of the pre-transplant screening. Patients with known human immunodeficiency virus infection, based on medical records serology. Patients with any uncontrolled infection at Randomization or a history of serious and uncontrolled infection within 6 months prior to Randomization. Patients who are pregnant or lactating. 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. 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. Patients who have previously participated in this study or any other study involving NPC-21. Patients who have previously participated or are currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent. 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. Patients who are unable or unwilling, in the opinion of the Investigator, to comply with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPC-21 Low dose<br>NPC-21 (Low dose) will be administered | Drug: NPC-21 Low dose<br>* NPC-21 will be administered via an approximately 60-minute intravenous infusion<br>|
| Experimental: NPC-21 High dose<br>NPC-21 (High dose) will be administered | Drug: NPC-21 High dose<br>* NPC-21 will be administered via an approximately 60-minute intravenous infusion<br>|
| Placebo Comparator: NPC-21 Placebo<br>Placebo (normal saline) will be administered | Drug: NPC-21 Placebo<br>* Placebo will be administered via an approximately 60-minute intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CMV disease or CMV viremia | Percentage of patients with adjudicated CMV disease or CMV viremia through 16 weeks post-transplant | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CMV disease or CMV viremia | Percentage of patients with adjudicated CMV disease or CMV viremia. | 28 weeks | 
| Incidence of CMV disease | Percentage of patients with adjudicated CMV disease | 28 weeks | 
| Incidence of CMV viremia | Percentage of patients with adjudicated CMV viremia. | 28 weeks | 
| Time to detectable CMV disease or CMV viremia |  | 28 weeks | 
| Time to detectable CMV disease |  | 28 weeks | 
| Time to detectable CMV viremia |  | 28 weeks | 
| Amount of CMV DNA |  | 28 weeks | 
| Incidence and duration of anti-CMV therapy during the Rescue Phase |  | 28 weeks | 
| Changes in EQ-5D-5L score from Baseline |  | 28 weeks |