Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Mycophenolate Mofetil · 3 trials · 2 indications
The composite efficacy endpoint consisted of treated biopsy proven acute rejection (BPAR) episodes, graft loss, death or loss to follow-up. A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. For the individual components (including loss of follow-up)of the composite endpoint, patients are counted for the first event to occur.
Renal function was assessed by glomerular filtration rate (GFR) using the MDRD formula: GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R C is the serum concentration of creatinine \[mg/dL\] A is age \[years\] G = 0.742 when gender is female, otherwise G=1 R = 1.21 when race is black, otherwise R=1 Loss to follow up (in In Primary Core Outcome Measure) is composite efficacy failure and contains incidence of treated BPAR, graft loss, death or loss to follow-up
Composite efficacy failure was defined as Biopsy Proven Acute Rejection(BPAR) of International Society for Heart and Lung Transplantation(ISHLT) grade ≥3A, Acute Rejection associated with Hemodynamic Compromise, Graft loss/Retransplant, Death or Loss to follow-up. Identification of acute rejection was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤30% or 25% lower than Baseline or Fractional shortening ≤20% or 25% lower than Baseline and/or use of inotropic treatment.
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 |
|---|---|---|
| Everolimus + Reduced dose of cyclosporine | EXPERIMENTAL | An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8 ng/mL). Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. Everolimus was available after 24 months for compassionate use. |
| Mycophenolate mofetil (MMF) + Standard dose of cyclosporine | ACTIVE_COMPARATOR | Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. |
| everolimus 1.5 mg | EXPERIMENTAL | Within 72 hours after transplantation participants received 0.75 mg everolimus tablets twice a day 12 hours apart for a total 1.5 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months. The everolimus dose could be adjusted to maintain a target everolimus trough level of 3-8 ng/mL. |
| everolimus 3.0 mg | EXPERIMENTAL | Within 72 hours after transplantation participants received 1.5 mg everolimus tablets twice a day 12 hours apart for a total 3.0 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months. The everolimus dose could be adjusted to maintain a target everolimus trough level of 6-12 ng/mL. Randomization of new patients in this arm was prematurely stopped as of 27 March 2008 due to high mortality rate, as per Data Monitoring Committee. |
| mycophenolate mofetil | ACTIVE_COMPARATOR | Within 72 hours after transplantation participants received 3 tablets 500 mg mycophenolate mofetil twice a day 12 hours apart for a total daily dose of 3000 mg in combination with a standard cyclosporine dose and standard dose corticosteroids for 24 months. |
| 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 |
|---|---|---|
| Everolimus | DRUG | 0.75 mg twice daily, trough level adjusting between 3 and 8 ng/ml. |
| Mycophenolate mofetil (MMF) | DRUG | The initial dose of 2 gm/day Mycophenolate mofetil was started within 24-36 hours from reperfusion after transplantation. MMF was administered daily for 12 months in the core study and 12 months in the extension study. |
| Basiliximab | DRUG | Patients received first dose of basiliximab (20 mg) 2 hours prior to transplantation and 20 mg at Day 4 or according to local practice |
| Cyclosporine A | DRUG | The cyclosporine was initiated either pre-transplant or within 24 hours after transplantation following local regime. Standard dose of cyclosporine was administered with MMF. The Reduced dose of cyclosporine was administered with everolimus. |
| Corticosteroid | DRUG | Corticosteroid was administered according to local practice during the trial but at a dose not less than 5mg per day for 12 months of the study |
| mycophenolate mofetil | DRUG | Mycophenolate mofetil supplied as 500 mg tablets. |
| cyclosporine | DRUG | Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm. |
| corticosteroids | DRUG | Corticosteroids standard dose. |
| CFZ533 - Cohort 1/Cohort 2 | BIOLOGICAL | CFZ533 was administered either by intravenous infusion or subcutaneous injection |
| 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. |
Core Study Inclusion Criteria: * Male or female de novo renal transplant recipients between 18 and 65 years of age * Patients who are receiving a primary cadaveric donor or non-human leukocyte antigen (non-HLA) identical living donor kidney transplant * Patients who have given written informed cons...
Mycophenolate Mofetil is used in kidney transplantation to prevent graft rejection. It is being studied in Phase 3 clinical trials for kidney transplant recipients, where it is compared against other immunosuppressive regimens to evaluate its efficacy and safety in preventing organ rejection.
Mycophenolate Mofetil is developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. Novartis is conducting clinical trials to evaluate the drug's use in kidney transplantation and graft rejection prevention.
Mycophenolate Mofetil is in Phase 3 clinical development for kidney transplantation and graft rejection. It has completed multiple Phase 3 trials, including studies with over 700 participants, though it remains an investigational drug in this context and is not yet approved for these indications.
Mycophenolate Mofetil has been evaluated in completed Phase 3 trials including NCT00300274, which studied heart transplant recipients to prevent graft rejection with 721 participants, and NCT00658320, a renal transplant study in Japan with 122 participants. Another trial, NCT01025817, compared it to everolimus in kidney transplant recipients.
Mycophenolate Mofetil is the generic name for the drug originally marketed as CellCept by Roche. However, the data provided does not mention CellCept or any alternative brand names, so no equivalence can be confirmed from the available information.