Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CFZ533- Cohort 1 · 1 trial · 1 indication
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.
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.
| Arm | Type | Description |
|---|---|---|
| Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids | EXPERIMENTAL | Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit. |
| Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids | EXPERIMENTAL | Eligible patients were randomized to CFZ533 300 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 300 mg sc (1 injection of 2 mL CFZ533 at 150 mg/mL, and 1 injection of 2 mL of the generic placebo) sc, Q2W, up to a planned Month 59.5 visit. |
| Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids | ACTIVE_COMPARATOR | Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids. |
| Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids | EXPERIMENTAL | Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 were administered sc at 450 mg (1 injection of 2 mL \& 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit. |
| Arm 2/Cohort 2: TAC + MMF ± Corticosteroids | ACTIVE_COMPARATOR | Patients received TAC-based regimen throughout the study. |
| Name | Type | Description |
|---|---|---|
| CFZ533 - Cohort 1/Cohort 2 | BIOLOGICAL | CFZ533 was administered either by intravenous infusion or subcutaneous injection |
| Mycophenolate Mofetil (MMF) | DRUG | Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously. |
| Corticosteroids (CS) | DRUG | Taken either orally or intravenously. |
| Tacrolimus | DRUG | Standard of care immunosuppressive regimen |
| Induction therapy: basiliximab | DRUG | Lyophilized solution taken intravenously |
| Induction therapy: rabbit anti-thymocyte globulin (rATG) | DRUG | Lyophilized vial taken intravenously. |
| Maintenance population: EC-MPS | DRUG | Tablet that is taken orally |
| Maintenance population: MMF | DRUG | Tablet that is taken orally |
| Placebo 1 mL | DRUG | Solution taken subcutaneously and was used for blinding of the CFZ533 doses. |
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 kid...