Kidney Transplantation
Conditions
Brief summary
This study will compare the incidence of acute clinical or subclinical rejection between immunosuppression with CellCept at a starting dose of 3mg po daily with therapeutic drug monitoring and standard immunosuppression with CellCept and a fixed dose of 2g po daily, in kidney transplant recipients receiving induction by anti-IRL2, cyclosporine therapy, and early discontinuation of steroids. Patients will be randomized to one of the two treatment arms. The anticipated time on study treatment is 52 weeks.
Interventions
DRUGmycophenolate mofetil
3 g p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing to Week 52, adapted to MPA by AUC on Weeks 2, 6, 12, 26, and 52 to obtain AUC0-12 of 50 milligrams (mg) multiplied by (\*) height (h)/ liter(L).
DRUGanti-IL-2R
Induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion.
DRUGmethylprednisolone
500 mg intravenous (i.v.) was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 to Day 7.
DRUGcyclosporine
100-1500 nanograms (ng) per milliliter (mL) from Day 0 to Week 4, 800-1200 ng/mL from Week 4 to Week 12 and 500-800 ng/mL from Week 12 to Week 52
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, aged 18-75 years of age; * in receipt of first donor kidney; * eligible to receive immunosuppressive treatment comprising IRL2, CellCept, cyclosporine and steroids; * eligible to receive oral treatment from the first day post-transplantation.
Exclusion criteria
* patients receiving a second or subsequent kidney transplant, or multi-organ transplant; * history of malignancy in the last 5 years (except successfully treated squamous cell or basal cell cancer and cervical cancer in situ); * patients with active hepatitis B and/or hepatitis C, or HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12 | Week 12 | BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10 percent (%) compared to baseline (BL) values and BPAR of Grade greater than or equal to (≥) 1 according to Banff 1997 classification at Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the Cockcroft-Gault equation. |
| Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the MDRD simplified equation. For males, the MDRD simplified equation was defined as MDRD (mL/min/1.73 square meters \[m\^2\]) =186 multiplied by (\*) serum creatinine in mg/L raised to the power of (\^) -1.154 \* age \^ -0.203. For females, the MDRD simplified equation was defined as MDRD (mL/min/1.73 m\^2) = males formula \* 0.742. |
| Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event | Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Time to Occurrence of First BPAR Between Day 0 and Week 52 | Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Percentage of Participants With at Least One BPAR at Week 12 and Week 52 | Weeks 12 and 52 | BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52. |
| Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 | Weeks 12 and 52 | Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Graft Loss - Percentage of Participants With an Event | Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | Graft loss was defined as physical loss (nephrectomy), functional loss \[necessitating maintenance dialysis for greater than (\>)8 weeks\], retransplant or death. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Time to Graft Loss | Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | The median time, in days, from randomization to graft loss event. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Participant Survival | Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 | Participants survival was defined as the percentage of participants living with or without a functioning graft between Weeks 0 and 52. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
| Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 | Weeks 12 and 52 | Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mycophenolate Mofetil, Adapted Dose Participants received MMF, 3 g, tablets or capsules, PO, q12h adapted to MPA by AUC on Day -1 or Day 0 through Week 52. Participants also received cyclosporine adapted to a C2 level = 1000 to 1500 ng/mL from Day 0 to Week 4, C2 = 800 to 1200 ng/mL from Weeks 4 to 12, and C2 = 500 to 800 ng/mL from Weeks 12 to 52. Participants also received methylprednisolone 500 mg, IV, on Day -1 or Day 0, and 0.5 mg/kg, PO, daily (maximum daily dose of 60 mg) from Days 1 through 7 (with steroid withdrawal on Day 7). Participants also received anti-IL-2R, per the investigator's discretion. | 126 |
| Mycophenolate Mofetil, Fixed Dose Participants received MMF 2 g, tablets or capsules, PO, q12h on Day -1 or Day 0 through Week 52. Participants also received cyclosporine adapted to C2 = 1000 to 1500 ng/mL from Day 0 to Week 4, C2 = 800 to 1200 ng/mL from Weeks 4 to 12, and C2 = 500 to 800 ng/mL from Weeks 12 to 52 and methylprednisolone 500 mg, IV, on Day -1 or Day 0, and 0.5 mg/kg, PO, daily (maximum daily dose of 60 mg) from Days 1 through 7 (with steroid withdrawal on Day 7). Participants also received anti-IL-2R, per the investigator's discretion. | 121 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 2 |
| Overall Study | Graft loss | 7 | 6 |
| Overall Study | No transplant | 1 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil, Adapted Dose | Mycophenolate Mofetil, Fixed Dose | Total |
|---|---|---|---|
| Age, Continuous | 48.4 years STANDARD_DEVIATION 13.2 | 48.5 years STANDARD_DEVIATION 13 | 48.5 years STANDARD_DEVIATION 13.1 |
| Sex: Female, Male Female | 40 Participants | 43 Participants | 83 Participants |
| Sex: Female, Male Male | 86 Participants | 78 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 120 / 127 | 115 / 125 |
| serious Total, serious adverse events | 106 / 127 | 94 / 125 |
Outcome results
Primary
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10 percent (%) compared to baseline (BL) values and BPAR of Grade greater than or equal to (≥) 1 according to Banff 1997 classification at Week 12.
Time frame: Week 12
Population: ITT population; only participants with available protocol biopsy at Week 12 and/or a BPAR before Week 12 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12 | 24.2 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12 | 19.8 percentage of participants |
p-value: 0.479Chi-squared
Secondary
Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min])
The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the Cockcroft-Gault equation.
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 2 (n=120,114) | 46.68 mL/min | Standard Deviation 21.05 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 4 (n=119,113) | 51.03 mL/min | Standard Deviation 19.17 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 6 (n=119,113) | 53.66 mL/min | Standard Deviation 20.94 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 12 (n=117,112) | 56.55 mL/min | Standard Deviation 19.4 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 16 (n=116,112) | 56.55 mL/min | Standard Deviation 20.14 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 26 (n=115,112) | 60.21 mL/min | Standard Deviation 21.35 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 40 (n=114,108) | 59.17 mL/min | Standard Deviation 19.86 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 52 (n=115,110) | 58.29 mL/min | Standard Deviation 20.42 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 52 (n=115,110) | 56.45 mL/min | Standard Deviation 22.02 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 2 (n=120,114) | 45.26 mL/min | Standard Deviation 18.93 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 16 (n=116,112) | 53.49 mL/min | Standard Deviation 19.72 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 4 (n=119,113) | 46.73 mL/min | Standard Deviation 18.11 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 40 (n=114,108) | 56.81 mL/min | Standard Deviation 21.81 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 6 (n=119,113) | 49.77 mL/min | Standard Deviation 19.05 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 26 (n=115,112) | 55.18 mL/min | Standard Deviation 20.52 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min]) | Week 12 (n=117,112) | 53.01 mL/min | Standard Deviation 20.14 |
p-value: 0.2172ANOVA
Secondary
Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation
The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the MDRD simplified equation. For males, the MDRD simplified equation was defined as MDRD (mL/min/1.73 square meters \[m\^2\]) =186 multiplied by (\*) serum creatinine in mg/L raised to the power of (\^) -1.154 \* age \^ -0.203. For females, the MDRD simplified equation was defined as MDRD (mL/min/1.73 m\^2) = males formula \* 0.742.
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 2 (n=120,114) | 40.61 mL/min/1.73 m^2 | Standard Deviation 19 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 4 (n=119,113) | 45.02 mL/min/1.73 m^2 | Standard Deviation 16.58 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 6 (n=119,113) | 48.12 mL/min/1.73 m^2 | Standard Deviation 19.32 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 12 (n=117,112) | 50.93 mL/min/1.73 m^2 | Standard Deviation 16.27 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 16 (n=116,112) | 50.93 mL/min/1.73 m^2 | Standard Deviation 17.05 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 26 (n=115,112) | 54.22 mL/min/1.73 m^2 | Standard Deviation 16.76 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 40 (n=114,108) | 52.23 mL/min/1.73 m^2 | Standard Deviation 15.94 |
| Mycophenolate Mofetil, Adapted Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 52 (n=115,110) | 50.82 mL/min/1.73 m^2 | Standard Deviation 16.33 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 52 (n=115,110) | 48.88 mL/min/1.73 m^2 | Standard Deviation 18.24 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 2 (n=120,114) | 39.60 mL/min/1.73 m^2 | Standard Deviation 18.74 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 16 (n=116,112) | 48.52 mL/min/1.73 m^2 | Standard Deviation 17.42 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 4 (n=119,113) | 41.31 mL/min/1.73 m^2 | Standard Deviation 16.7 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 40 (n=114,108) | 50.01 mL/min/1.73 m^2 | Standard Deviation 18.69 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 6 (n=119,113) | 44.69 mL/min/1.73 m^2 | Standard Deviation 16.69 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 26 (n=115,112) | 49.46 mL/min/1.73 m^2 | Standard Deviation 18.64 |
| Mycophenolate Mofetil, Fixed Dose | Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation | Week 12 (n=117,112) | 47.68 mL/min/1.73 m^2 | Standard Deviation 16.24 |
p-value: 0.477ANOVA
Secondary
Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52
Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Weeks 12 and 52
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 | Week 12 | 7.9 percentage of participants |
| Mycophenolate Mofetil, Adapted Dose | Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 | Week 52 | 6.4 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 | Week 12 | 12.4 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 | Week 52 | 5.0 percentage of participants |
Comparison: Week 12p-value: 0.245Fisher Exact
Comparison: Week 52p-value: 0.637Fisher Exact
Secondary
Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52
Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Weeks 12 and 52
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 | Week 12 | 20.6 percentage of participants |
| Mycophenolate Mofetil, Adapted Dose | Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 | Week 52 | 32.5 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 | Week 12 | 17.4 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 | Week 52 | 34.7 percentage of participants |
p-value: 0.512Fisher Exact
p-value: 0.718Fisher Exact
Secondary
Graft Loss - Percentage of Participants With an Event
Graft loss was defined as physical loss (nephrectomy), functional loss \[necessitating maintenance dialysis for greater than (\>)8 weeks\], retransplant or death. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Graft Loss - Percentage of Participants With an Event | 5.6 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Graft Loss - Percentage of Participants With an Event | 5.0 percentage of participants |
Secondary
Participant Survival
Participants survival was defined as the percentage of participants living with or without a functioning graft between Weeks 0 and 52. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Participant Survival | 98.4 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Participant Survival | 98.3 percentage of participants |
Secondary
Percentage of Participants With at Least One BPAR at Week 12 and Week 52
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Weeks 12 and 52
Population: ITT population; only participants with at least one assessed biopsy were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Percentage of Participants With at Least One BPAR at Week 12 and Week 52 | Week 12 | 14.1 percentage of participants |
| Mycophenolate Mofetil, Adapted Dose | Percentage of Participants With at Least One BPAR at Week 12 and Week 52 | Week 52 | 9.1 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Percentage of Participants With at Least One BPAR at Week 12 and Week 52 | Week 12 | 10.0 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Percentage of Participants With at Least One BPAR at Week 12 and Week 52 | Week 52 | 10.0 percentage of participants |
Comparison: Week 12p-value: 0.418Fisher Exact
Comparison: Week 52p-value: 0.841Fisher Exact
Secondary
Serum Creatinine Values [Micromoles Per Liter (µmol/L)]
The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52.
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population; number (n) = number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 2 (n=120,114) | 202.41 µmol/L | Standard Deviation 144.8 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 16 (n=116,112) | 145.48 µmol/L | Standard Deviation 83 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 6 (n=119,113) | 155.74 µmol/L | Standard Deviation 84.01 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 4 (n=119,113) | 168.92 µmol/L | Standard Deviation 95.66 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 40 (n=114,108) | 136.24 µmol/L | Standard Deviation 45.84 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 12 (n=117,112) | 140.80 µmol/L | Standard Deviation 53.18 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 52 (n=115,110) | 148.62 µmol/L | Standard Deviation 124.3 |
| Mycophenolate Mofetil, Adapted Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 26 (n=115,112) | 131.73 µmol/L | Standard Deviation 42.2 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 52 (n=115,110) | 144.72 µmol/L | Standard Deviation 47.37 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 2 (n=120,114) | 201.31 µmol/L | Standard Deviation 130.79 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 4 (n=119,113) | 174.86 µmol/L | Standard Deviation 77.67 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 6 (n=119,113) | 158.96 µmol/L | Standard Deviation 59.36 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 12 (n=117,112) | 147.70 µmol/L | Standard Deviation 50.38 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 16 (n=116,112) | 148.48 µmol/L | Standard Deviation 71.83 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 26 (n=115,112) | 143.73 µmol/L | Standard Deviation 46.87 |
| Mycophenolate Mofetil, Fixed Dose | Serum Creatinine Values [Micromoles Per Liter (µmol/L)] | Week 40 (n=114,108) | 141.89 µmol/L | Standard Deviation 47.19 |
p-value: 0.6736ANOVA
Secondary
Time to Graft Loss
The median time, in days, from randomization to graft loss event. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Time to Graft Loss | NA days |
| Mycophenolate Mofetil, Fixed Dose | Time to Graft Loss | NA days |
p-value: 0.86Log Rank
Secondary
Time to Occurrence of First BPAR Between Day 0 and Week 52
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Time to Occurrence of First BPAR Between Day 0 and Week 52 | NA days |
| Mycophenolate Mofetil, Fixed Dose | Time to Occurrence of First BPAR Between Day 0 and Week 52 | NA days |
p-value: 0.0764Log Rank
Secondary
Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event | 24.6 percentage of participants |
| Mycophenolate Mofetil, Fixed Dose | Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event | 14.9 percentage of participants |