Trial Outcomes & Findings for OPERA Study: A Study of Two Dosing Regimens of CellCept (Mycophenolate Mofetil) in Kidney Transplant Patients. (NCT NCT02005562)

NCT ID: NCT02005562

Last Updated: 2015-11-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

Week 12

Results posted on

2015-11-11

Participant Flow

Participant milestones

Participant milestones
Measure	Mycophenolate Mofetil, Adapted Dose Participants received mycophenolate mofetil (MMF), 3 grams (g), tablets or capsules, orally (PO), every 12 hours (q12h) adapted to mycophenolic acid (MPA) by area under the curve (AUC) on Day -1 or Day 0 through Week 52. Participants also received cyclosporine adapted to a 2 hour postdose (C2) level equal to (=) 1000 to 1500 nanograms per milliliter (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 milligrams (mg), intravenously (IV), on Day -1 or Day 0, and 0.5 mg per kilogram (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-interleukin (IL)-2R, per the investigator's discretion.	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.
Overall Study STARTED	127	125
Overall Study Transplanted	126	121
Overall Study COMPLETED	115	110
Overall Study NOT COMPLETED	12	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Mycophenolate Mofetil, Adapted Dose Participants received mycophenolate mofetil (MMF), 3 grams (g), tablets or capsules, orally (PO), every 12 hours (q12h) adapted to mycophenolic acid (MPA) by area under the curve (AUC) on Day -1 or Day 0 through Week 52. Participants also received cyclosporine adapted to a 2 hour postdose (C2) level equal to (=) 1000 to 1500 nanograms per milliliter (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 milligrams (mg), intravenously (IV), on Day -1 or Day 0, and 0.5 mg per kilogram (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-interleukin (IL)-2R, per the investigator's discretion.	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.
Overall Study Death	2	2
Overall Study Graft loss	7	6
Overall Study Withdrawal by Subject	2	2
Overall Study No transplant	1	4
Overall Study Physician Decision	0	1

Baseline Characteristics

OPERA Study: A Study of Two Dosing Regimens of CellCept (Mycophenolate Mofetil) in Kidney Transplant Patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.	Total n=247 Participants Total of all reporting groups
Age, Continuous	48.4 years STANDARD_DEVIATION 13.2 • n=5 Participants	48.5 years STANDARD_DEVIATION 13.0 • n=7 Participants	48.5 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	43 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	78 Participants n=7 Participants	164 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=91 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=86 Participants 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.
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	19.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=120 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=114 Participants 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.
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 2 (n=120,114)	202.41 µmol/L Standard Deviation 144.80	201.31 µmol/L Standard Deviation 130.79
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 4 (n=119,113)	168.92 µmol/L Standard Deviation 95.66	174.86 µmol/L Standard Deviation 77.67
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 6 (n=119,113)	155.74 µmol/L Standard Deviation 84.01	158.96 µmol/L Standard Deviation 59.36
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 12 (n=117,112)	140.80 µmol/L Standard Deviation 53.18	147.70 µmol/L Standard Deviation 50.38
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 16 (n=116,112)	145.48 µmol/L Standard Deviation 83.00	148.48 µmol/L Standard Deviation 71.83
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 26 (n=115,112)	131.73 µmol/L Standard Deviation 42.20	143.73 µmol/L Standard Deviation 46.87
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 40 (n=114,108)	136.24 µmol/L Standard Deviation 45.84	141.89 µmol/L Standard Deviation 47.19
Serum Creatinine Values [Micromoles Per Liter (µmol/L)] Week 52 (n=115,110)	148.62 µmol/L Standard Deviation 124.30	144.72 µmol/L Standard Deviation 47.37

SECONDARY outcome

Timeframe: 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.

The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the Cockcroft-Gault equation.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=120 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=114 Participants 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.
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	45.26 mL/min Standard Deviation 18.93
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	46.73 mL/min Standard Deviation 18.11
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	49.77 mL/min Standard Deviation 19.05
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 19.40	53.01 mL/min Standard Deviation 20.14
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	53.49 mL/min Standard Deviation 19.72
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	55.18 mL/min Standard Deviation 20.52
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	56.81 mL/min Standard Deviation 21.81
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	56.45 mL/min Standard Deviation 22.02

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=120 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=114 Participants 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.
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	44.69 mL/min/1.73 m^2 Standard Deviation 16.69
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 19.00	39.60 mL/min/1.73 m^2 Standard Deviation 18.74
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	41.31 mL/min/1.73 m^2 Standard Deviation 16.70
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	47.68 mL/min/1.73 m^2 Standard Deviation 16.24
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	48.52 mL/min/1.73 m^2 Standard Deviation 17.42
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	49.46 mL/min/1.73 m^2 Standard Deviation 18.64
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	50.01 mL/min/1.73 m^2 Standard Deviation 18.69
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	48.88 mL/min/1.73 m^2 Standard Deviation 18.24

SECONDARY outcome

Timeframe: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event	24.6 percentage of participants	14.9 percentage of participants

SECONDARY outcome

Timeframe: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52

Population: ITT population

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Time to Occurrence of First BPAR Between Day 0 and Week 52	NA days Median time to occurrence of first BPAR was not reached as follow-up time was too short to observe enough events for complete data estimation.	NA days Median time to occurrence of first BPAR was not reached as follow-up time was too short to observe enough events for complete data estimation.

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: ITT population; only participants with at least one assessed biopsy were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=88 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=80 Participants 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.
Percentage of Participants With at Least One BPAR at Week 12 and Week 52 Week 12	14.1 percentage of participants	10.0 percentage of participants
Percentage of Participants With at Least One BPAR at Week 12 and Week 52 Week 52	9.1 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: ITT population

Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 Week 12	7.9 percentage of participants	12.4 percentage of participants
Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 Week 52	6.4 percentage of participants	5.0 percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: ITT population

Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
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	17.4 percentage of participants
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	34.7 percentage of participants

SECONDARY outcome

Timeframe: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Graft Loss - Percentage of Participants With an Event	5.6 percentage of participants	5.0 percentage of participants

SECONDARY outcome

Timeframe: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Time to Graft Loss	NA days Full Range NA Median time to graft loss was not reached as follow-up time was too short to observe enough events for complete data estimation.	NA days Full Range NA Median time to graft loss was not reached as follow-up time was too short to observe enough events for complete data estimation.

SECONDARY outcome

Timeframe: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	Mycophenolate Mofetil, Adapted Dose n=126 Participants 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.	Mycophenolate Mofetil, Fixed Dose n=121 Participants 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.
Participant Survival	98.4 percentage of participants	98.3 percentage of participants

Adverse Events

Mycophenolate Mofetil, Adapted Dose

Serious events: 106 serious events

Other events: 120 other events

Deaths: 0 deaths

Mycophenolate Mofetil, Fixed Dose

Serious events: 94 serious events

Other events: 115 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Mycophenolate Mofetil, Adapted Dose n=127 participants at risk 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.	Mycophenolate Mofetil, Fixed Dose n=125 participants at risk 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.
Blood and lymphatic system disorders Anaemia	55.9% 71/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	49.6% 62/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Blood and lymphatic system disorders Leukopenia	33.1% 42/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	18.4% 23/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Gastrointestinal disorders Diarrheoa	14.2% 18/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	4.8% 6/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
General disorders Oedema peripheral	21.3% 27/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	21.6% 27/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Infections and infestations Cytomegalovirus infection	11.8% 15/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	11.2% 14/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Infections and infestations Urinary tract infection	22.0% 28/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	24.8% 31/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Injury, poisoning and procedural complications Graft dysfunction	17.3% 22/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	8.0% 10/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Investigations Blood creatinine increased	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	9.6% 12/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Renal and urinary disorders Kidney transplant rejection	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	3.2% 4/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Renal and urinary disorders Dysuria	4.7% 6/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	5.6% 7/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Vascular disorders Hypertension	14.2% 18/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	17.6% 22/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Blood and lymphatic system disorders Iron deficiency anaemia	3.1% 4/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	5.6% 7/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Blood and lymphatic system disorders Neutropenia	7.9% 10/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	9.6% 12/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Gastrointestinal disorders Abdominal pain upper	6.3% 8/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	4.0% 5/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Gastrointestinal disorders Gastrointestinal disorder	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	0.00% 0/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Gastrointestinal disorders Gingival hypertrophy	7.9% 10/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	4.8% 6/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
General disorders Pyrexia	6.3% 8/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	5.6% 7/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Renal and urinary disorders Proteinuria	7.1% 9/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	6.4% 8/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Infections and infestations Bronchitis	3.1% 4/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	5.6% 7/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Infections and infestations Herpes simplex	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	1.6% 2/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Metabolism and nutrition disorders Dyslipidaemia	10.2% 13/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	13.6% 17/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Metabolism and nutrition disorders Diabetes mellitus	12.6% 16/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	9.6% 12/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Metabolism and nutrition disorders Hyperkalaemia	3.9% 5/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	7.2% 9/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Metabolism and nutrition disorders Overweight	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	4.0% 5/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Metabolism and nutrition disorders Underweight	5.5% 7/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	2.4% 3/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.
Respiratory, thoracic and mediastinal disorders Cough	2.4% 3/127 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.	5.6% 7/125 • All adverse events (AEs) were recorded from randomization (Day 0) through the end of study (Week 52). Safety population: all randomized participants administered at least 1 study treatment dose.