Cytomegalovirus Disease
Conditions
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)
Interventions
DRUGNPC-21 Low dose
NPC-21 will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12
DRUGNPC-21 High dose
NPC-21 will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12
DRUGNPC-21 Placebo
Placebo will be administered via an approximately 60-minute intravenous infusion on Day 1 and at Week 4, 8, 12
Sponsors
Nobelpharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CMV Disease or CMV Viremia | 16 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CMV Disease | 28 weeks | The proportion of patients with CMV disease |
| Incidence of CMV Viremia | 28 weeks | The proportion of patients with CMV viremia. |
| Incidence of CMV Disease or CMV Viremia | 28 weeks | 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. |
| Time to Detectable CMV Disease | 28 weeks | The count and proportion of patients experiencing event and censored will be summarized by treatment group. |
| Time to Detectable CMV Viremia | 28 weeks | The count and proportion of patients experiencing event and censored will be summarized by treatment group. |
| Time to Detectable CMV Disease or CMV Viremia | 28 weeks | The count and proportion of patients experiencing event and censored will be summarized by treatment group. |
Countries
Japan, United States
Participant flow
Recruitment details
From June 2020 to August 2022, adult CMV seronegative patients who received a first kidney transplant from CMV seropositive donors were enrolled in the study at 31 sites in the United States and Japan.
Participants by arm
| Arm | Count |
|---|---|
| NPC-21 Low Dose NPC-21 (6mg/kg) will be administered
NPC-21 Low dose: NPC-21 will be administered via an approximately 60-minute intravenous infusion | 38 |
| NPC-21 High Dose NPC-21 (12mg/kg) will be administered
NPC-21 High dose: NPC-21 will be administered via an approximately 60-minute intravenous infusion | 11 |
| NPC-21 Placebo Placebo (normal saline) will be administered
NPC-21 Placebo: Placebo will be administered via an approximately 60-minute intravenous infusion | 38 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | A subject completed the study but was reported incorrectly in the report form | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | NPC-21 Low Dose | NPC-21 High Dose | NPC-21 Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 9 Participants | 31 Participants | 74 Participants |
| Age, Continuous | 50.4 years STANDARD_DEVIATION 12.45 | 50.5 years STANDARD_DEVIATION 15.65 | 51.7 years STANDARD_DEVIATION 14.04 | 51.0 years STANDARD_DEVIATION 13.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 3 Participants | 11 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 1 Participants | 10 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 6 Participants | 17 Participants | 42 Participants |
| Region of Enrollment Japan | 10 participants | 3 participants | 10 participants | 23 participants |
| Region of Enrollment United States | 28 participants | 8 participants | 28 participants | 64 participants |
| Sex: Female, Male Female | 15 Participants | 4 Participants | 15 Participants | 34 Participants |
| Sex: Female, Male Male | 23 Participants | 7 Participants | 23 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 11 | 0 / 38 |
| other Total, other adverse events | 33 / 38 | 9 / 11 | 34 / 38 |
| serious Total, serious adverse events | 17 / 38 | 3 / 11 | 25 / 38 |
Outcome results
Primary
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.
Time frame: 16 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NPC-21 Low Dose | Incidence of CMV Disease or CMV Viremia | 29 Participants |
| NPC-21 High Dose | Incidence of CMV Disease or CMV Viremia | 9 Participants |
| NPC-21 Placebo | Incidence of CMV Disease or CMV Viremia | 26 Participants |
Secondary
Incidence of CMV Disease
The proportion of patients with CMV disease
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NPC-21 Low Dose | Incidence of CMV Disease | 2 Participants |
| NPC-21 High Dose | Incidence of CMV Disease | 0 Participants |
| NPC-21 Placebo | Incidence of CMV Disease | 5 Participants |
Secondary
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.
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NPC-21 Low Dose | Incidence of CMV Disease or CMV Viremia | 29 Participants |
| NPC-21 High Dose | Incidence of CMV Disease or CMV Viremia | 9 Participants |
| NPC-21 Placebo | Incidence of CMV Disease or CMV Viremia | 26 Participants |
Secondary
Incidence of CMV Viremia
The proportion of patients with CMV viremia.
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NPC-21 Low Dose | Incidence of CMV Viremia | 22 Participants |
| NPC-21 High Dose | Incidence of CMV Viremia | 8 Participants |
| NPC-21 Placebo | Incidence of CMV Viremia | 17 Participants |
Secondary
Time to Detectable CMV Disease
The count and proportion of patients experiencing event and censored will be summarized by treatment group.
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NPC-21 Low Dose | Time to Detectable CMV Disease | NA weeks |
| NPC-21 High Dose | Time to Detectable CMV Disease | NA weeks |
| NPC-21 Placebo | Time to Detectable CMV Disease | NA weeks |
Secondary
Time to Detectable CMV Disease or CMV Viremia
The count and proportion of patients experiencing event and censored will be summarized by treatment group.
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NPC-21 Low Dose | Time to Detectable CMV Disease or CMV Viremia | 6.1 weeks |
| NPC-21 High Dose | Time to Detectable CMV Disease or CMV Viremia | 6.3 weeks |
| NPC-21 Placebo | Time to Detectable CMV Disease or CMV Viremia | 6.3 weeks |
Secondary
Time to Detectable CMV Viremia
The count and proportion of patients experiencing event and censored will be summarized by treatment group.
Time frame: 28 weeks
Population: All patients who received a kidney transplant from a living or deceased donor and received at least 1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NPC-21 Low Dose | Time to Detectable CMV Viremia | 6.1 weeks |
| NPC-21 High Dose | Time to Detectable CMV Viremia | 6.3 weeks |
| NPC-21 Placebo | Time to Detectable CMV Viremia | NA weeks |