Kidney Transplantation
Conditions
Keywords
Kidney Transplant Rejection, Renal transplantation, CFZ533, CNI-free immunosuppression, transplant rejection, allograft rejection
Brief summary
This study was to compare CFZ533 to tacrolimus (TAC) in prevention of organ rejection in kidney transplant.
Detailed description
The purpose of this study was to investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of three CFZ533 dose regimens in kidney transplant recipients. Study CCFZ533A2201 was a randomized, planned 60-month (5 year) study comprising of 12-months treatment for the primary analysis plus an additional 48-month treatment period. The study had 2 different cohorts: adult de novo kidney transplant recipients and maintenance kidney transplant population (6-24 months post-transplant). The study was terminated after the interim analysis.
Interventions
BIOLOGICALCFZ533 - Cohort 1/Cohort 2
CFZ533 was administered either by intravenous infusion or subcutaneous injection
DRUGMycophenolate Mofetil (MMF)
Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.
Taken either orally or intravenously.
DRUGTacrolimus
Standard of care immunosuppressive regimen
DRUGInduction therapy: basiliximab
Lyophilized solution taken intravenously
DRUGInduction therapy: rabbit anti-thymocyte globulin (rATG)
Lyophilized vial taken intravenously.
DRUGMaintenance population: EC-MPS
Tablet that is taken orally
DRUGMaintenance population: MMF
Tablet that is taken orally
DRUGPlacebo 1 mL
Solution taken subcutaneously and was used for blinding of the CFZ533 doses.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria for both cohorts * Written informed consent obtained before any assessment. * Male or female patient ≥ 18 years old. * Up to date vaccination as per local immunization schedules. Key inclusion criteria specific to Cohort 1: * Recipients of a primary kidney transplant from a brain-dead donor, living unrelated or non-human leukocyte antigen (HLA) identical living related donors. * Recipients of a kidney with a cold ischemia time \< 24 hours. Key inclusion criteria specific to Cohort 2: * Recipients of a primary graft received 6 to 24 months prior enrollment, on a regimen containing TAC+MMF/ Enteric-coated mycophenolate sodium (EC-MPS)±corticosteroids (CS). * Patients with an actual eGFR according to Modification of Diet in Renal Disease (MDRD-4) ≥ 45 mL/min/1.73m2.
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1) | 12 Months | The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss. |
| Percentage of Participants With Composite Efficacy Failure Event (BPAR, Graft Loss or Death) Over 12 Months Post-conversion (Cohort 2) | 12 Months | The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation | 12 months | In the de novo population (Cohort 1), the mean eGFR at Month 12 post-transplantation was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula. |
| Cohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion | 12 months | In the maintenance population (Cohort 2), a baseline kidney function and the mean change from baseline at Month 12 post-conversion of eGFR was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula. |
| Free CFZ533 Plasma Concentrations Over Time (Cohort 1) | Day 1-Pre-Dose to Month 30-Pre-Dose | Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period. |
| Free CFZ533 Plasma Concentrations Over Time (Cohort 2) | Day 1-Pre-Dose to Month 30-Pre-Dose | Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period. |
| Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 1) | 24 Months | The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays. |
| Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 2) | 24 Months | The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Latvia, Netherlands, Norway, South Korea, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Recruitment details
Patients were enrolled at 74 sites. 403 patients were randomized.
Pre-assignment details
This study comprised of a screening period
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized >= 60 6years | 99 Participants |
| Age, Customized < 60 years | 304 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants |
| Race/Ethnicity, Customized Asian: Indian | 2 Participants |
| Race/Ethnicity, Customized Asian: Japanese | 12 Participants |
| Race/Ethnicity, Customized Asian: Korean | 4 Participants |
| Race/Ethnicity, Customized Asian: Other | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 14 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized Other - Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 84 Participants |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 291 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 403 | 2 / 108 | 5 / 108 | 2 / 108 | 0 / 109 | 1 / 109 | 0 / 109 | 1 / 73 | 0 / 73 | 0 / 73 | 0 / 70 | 1 / 70 | 0 / 70 | 1 / 42 | 1 / 42 | 0 / 42 |
| other Total, other adverse events | 0 / 0 | 105 / 108 | 20 / 108 | 0 / 0 | 102 / 109 | 19 / 109 | 0 / 0 | 67 / 73 | 4 / 73 | 0 / 0 | 54 / 70 | 4 / 70 | 0 / 0 | 26 / 42 | 0 / 42 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 71 / 108 | 18 / 108 | 0 / 0 | 76 / 109 | 19 / 109 | 0 / 0 | 39 / 73 | 3 / 73 | 0 / 0 | 25 / 70 | 4 / 70 | 0 / 0 | 11 / 42 | 1 / 42 | 0 / 0 |
Outcome results
None listed