Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication CELLCEPT [mycophenolate mofetil (MMF)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1) ], heart [see Clinical Studies (14.2) ] or liver transplants [see Clinical Studies (14.3) ] , in combination with other immunosuppressants.
Also known as mycophenolate mofetil, Mycophenolate mofetil (MMF), Mycophenoate Mofetil, MMF, Ro 70-0003, Prograf, Neoral
CellCept · 18 trials · 18 indications
Cmax was expressed in milligrams per liter (mg/L).
Cmax was expressed in mg/L.
Cmax was expressed in mg/L.
Cmax was expressed in mg/L.
Cmax was expressed in micrograms per liter (mcg/L).
Cmax was expressed in mcg/L.
Cmax was expressed in mcg/L.
Cmax was expressed in mcg/L.
Dose-normalized Cmax was determined (in 1 per liter \[1/L\]) by dividing the Cmax by the actual dose taken.
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Dose-normalized Cmax was determined (in 1/L) by dividing the Cmax by the actual dose taken.
Cmin was expressed in mg/L.
Cmin was expressed in mg/L.
Cmin was expressed in mg/L.
Cmin was expressed in mg/L.
Cmin was expressed in mcg/L.
Cmin was expressed in mcg/L.
Cmin was expressed in mcg/L.
Cmin was expressed in mcg/L.
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in liters per hour (L/hour).
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
CL is a quantitative measure of the rate at which a drug substance is removed from the body and expressed in L/hour.
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours time milligrams per liter (hours\*\[mg/L\]).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours times micrograms per liter (hours\*\[mcg/L\]).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours and expressed in hours\*(mcg/L).
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
AUC0-12 is a measure of the serum concentration of the drug from time 0 to 12 hours. Dose-normalized AUC0-12 was determined (in hours/L) by dividing the AUC0-12 by the actual dose taken.
MPA Free fraction (in percent \[%\]) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
MPA Free fraction (in %) was calculated by dividing free MPA AUC0-12 by total MPA AUC0-12 times 100%.
Percentage of participants with BPAR of greater than or equal to (≥) International Society of Heart and Lung Transplant (ISHLT) Grade III. The ISHLT graded symptoms on a scale of Grade 0 through VI. Grade 0 equals (=) no rejection. Grade IA = regional (perivascular or interstitial) infiltration and no necrosis, and grade IB = dissemination but little infiltration and no necrosis. Grade II = 1 focus of invasive infiltration with or without (+/-) associated cardiomyocyte necrosis. Grade IIIA = 2 or more foci of invasive infiltration +/- associated cardiomyocyte necrosis, and grade IIIB = diffuse inflammatory pathological changes associated with cardiomyocyte necrosis. Grade IV = diffuse, infiltrative multi-foci +/- edema; +/- hemorrhage; and +/-vasculitis.
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.
Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to \<3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria \<3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.
Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.
The proportion of subjects achieving responder status (defined as no new persistent lesions and prednisone dose of not more than 10 mg/day from Week 48 until study termination at Week 52) in the two active treatment groups combined (2 g/day and 3 g/day mycophenolate mofetil) compared with the placebo group
the percentage of subjects achieving at least partial remission of LN (PRR) as per the adapted ACR/EULAR Criteria at Week 26
Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio \< 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN range of central laboratory values.
The primary outcome is the course over time from baseline to 24 months for the FVC %-predicted. The FVC %-predicted represents the adjusted volume of air (adjusted as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity) that can be forcibly exhaled from the lungs after taking the deepest breath possible. The FVC %-predicted is reduced in patients with interstitial lung disease and is used as a measure of lung involvement and disease severity.
International Working Group (IWG) criteria for hematological improvement was defined as having hemoglobin (Hgb) \<11 g/dL (pretreatment) and an increase in Hgb ≥1.5 g/dL after ≥8 weeks of treatment.
Diagnosis of acute rejection was suspected in any participant with an increase in serum creatinine greater than or equal to (≥) 25 percent (%). All suspected acute rejections were confirmed by biopsy. The start date of acute rejection was identified as the date of biopsy.
The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.
BPAR was defined according to 1997 Banff Criteria as a biopsy Banff grade of IA, IB, IIA, IIB, or III. Grade IA was defined as significant interstitial infiltration with greater than (\>)25% of parenchyma affected, and foci of moderate tubulitis with \>4 mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IB was defined as significant interstitial infiltration with \>25% parenchyma affected, and foci of severe tubulitis with \>10% mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IIA was defined as mild to moderate intimal arteritis. Grade IIB was defined as severe intimal arteritis comprising \>25% of the luminal area. Grade III was defined as transmural arteritis and/or arterial fibrinoid changes and necrosis of medial smooth muscle cells.
| Arm | Type | Description |
|---|---|---|
| Mycophenolate Mofetil (MMF) | ACTIVE_COMPARATOR | Participants will receive MMF orally twice daily (every 12 hours, Q12H) from Day 1 to Week 52. Participants will also receive rituximab matching placebo by intravenous (IV) infusion on Days 1 and 15 with repeat administration on Days 168 and 182 provided specific safety criteria have been met. |
| Rituximab (RTX) | EXPERIMENTAL | Participants will receive rituximab by IV infusion on Days 1 and 15 with repeat administration on Days 168 and 182 provided specific safety criteria have been met. Participants will also receive MMF matching placebo orally twice daily Q12H from Day 1 to Week 52. |
| Mycophenolate Mofetil; Cystic Fibrosis | EXPERIMENTAL | Participants with cystic fibrosis will receive mycophenolate mofetil 1.5 g, orally (PO), BID from Days 2 through 30 post-transplantation, and 1 g, PO, BID from Days 31 through 90 post-transplantation. |
| Mycophenolate Mofetil; Other | EXPERIMENTAL | Participants with COPD, emphysema, idiopathic pulmonary fibrosis, or A1AD will receive mycophenolate mofetil 1.5 g, PO, BID, from Days 2 through 30 post-transplantation, and 1 g, PO, BID from Days 31 through 90 post-transplantation. |
| MMF, CsA, Corticosteroids | EXPERIMENTAL | Participants received mycophenolate mofetil (MMF) 1.0 grams (g), orally (PO), twice daily (BID) from within 24 hours of transplantation through Week 24. Participants also received an initial loading dose of cyclosporine A (CsA) 4 to 6 milligrams per kilogram (mg/kg) within 48 hours of transplantation, adjusted thereafter to a blood trough concentration of 150 to 300 nanograms per milliliter (ng/mL) through Week 24. Participants also received corticosteroids as per the practice of each participating center. |
| Mycophenolate Mofetil, Adapted Dose | EXPERIMENTAL | Participants received 3 grams (g) mycophenolate mofetil (MMF) tablets per os (p.o.) in divided doses (every 12 hours \[q12h\]) adapted to mycophenolic acid (MPA) by area under the curve (AUC) beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by interleukin-2R (IL-2R) was administered at Day 0 per standard of care at the site at the investigator's discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 nanograms (ng) per (/) milliliter (mL) from Day 0 to (-) Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg intravenously (i.v.) was administered before or after the transplantation, and 0.5 milligrams (mg) per kilogram (kg) p.o. daily from Day 1 - Day 7. |
| Mycophenolate Mofetil, Fixed Dose | ACTIVE_COMPARATOR | Participants received 2 g MMF tablets p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 ng/mL from Day 0 - Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg i.v. was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 - Day 7. |
| Induction Phase: Mycophenolate mofetil | EXPERIMENTAL | Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase. |
| Induction Phase: Cyclophosphamide | ACTIVE_COMPARATOR | Participants received monthly infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase. |
| Maintenance Phase: Mycophenolate mofetil | EXPERIMENTAL | Participants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase. |
| Maintenance Phase: Azathioprine | ACTIVE_COMPARATOR | Participants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase. |
| 1 | EXPERIMENTAL | - |
| Mycophenolate Mofetil + Cyclosporine | ACTIVE_COMPARATOR | Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. |
| Mycophenolate Mofetil + Sirolimus | EXPERIMENTAL | Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. |
| 2 | PLACEBO_COMPARATOR | - |
| Mycophenolate Mofetil (MMF) 2 g/Day | EXPERIMENTAL | Mycophenolate mofetil 500 mg tablets; 4 tablets twice daily for 52 weeks |
| Mycophenolate Mofetil (MMF) 3 g/Day | EXPERIMENTAL | Mycophenolate mofetil 500 mg tablets; 6 tablets twice daily for 52 weeks |
| Placebo | PLACEBO_COMPARATOR | - |
| 3 | EXPERIMENTAL | - |
| MMFBSA | ACTIVE_COMPARATOR | MMF dosed as per body-surface area |
| MMFPK | EXPERIMENTAL | MMF dosed as per pharmacokinetically-guided precision-dosing |
| Obinutuzumab | EXPERIMENTAL | Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12. |
| Mycophenolate Arm | EXPERIMENTAL | Participants will receive oral mycophenolate mofetil for 2 years. |
| Cyclophosphamide Arm | EXPERIMENTAL | Participants will receive oral cyclophosphamide for 1 year, followed by placebo for 1 year. |
| Mycophenolate Mofetil + Prednisone + Erythropoietin Beta | EXPERIMENTAL | Mycophenolate mofetil (MMF) 1 gm twice daily orally and prednisone 10 mg/day orally until the end of the study. Recombinant human erythropoietin beta 30,000 IU/week, subcutaneously for 6 weeks was added in case of no significant response at Week 12. |
| Mycophenolate Mofetil Monotherapy | EXPERIMENTAL | Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice. |
| Name | Type | Description |
|---|---|---|
| Mycophenolate Mofetil Placebo | DRUG | MMF matching placebo will be administered orally Q12H. |
| Mycophenolate Mofetil | DRUG | MMF will be administered at a starting dose of 500 milligrams (mg) Q12H and the dose will be titrated to achieve a goal of 1 gram (gm) Q12H. |
| Rituximab | DRUG | Rituximab will be administered at a dose of 1000 mg via IV infusion. |
| Rituximab Placebo | DRUG | Rituximab matching placebo will be administered via IV infusion. |
| mycophenolate mofetil (MMF) | DRUG | 1.0 g PO BID |
| cyclosporine A (CsA) | DRUG | Initial loading dose of 4 to 6 mg/kg within 48 hours of transplantation, adjusted thereafter to a blood trough concentration of 150 to 300 ng/mL |
| corticosteroids | DRUG | As per the practice of each participating center |
| anti-IL-2R | DRUG | Induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion. |
| methylprednisolone | DRUG | 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. |
| cyclosporine | DRUG | 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 |
| Cyclophosphamide | DRUG | Intravenous cyclophosphamide (IVC) was administered every four weeks (monthly) to a total of six infusions. Dosing was started at 0.75 g/m\^2 of body surface area for the first month, with subsequent doses at 0.5-1.0 g/m\^2. The target dose was 1.0 g/m\^2, but doses were titrated by 0.25 g/m\^2 increments to maintain nadir leukocyte count between 2500-4000/mm\^3. |
| Azathioprine | DRUG | 2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals. |
| Placebo to Azathioprine | DRUG | Placebo capsules matching Azathioprine taken orally once a day. |
| Placebo to Mycophenolate mofetil | DRUG | Placebo tablets matching Mycophenolate mofetil taken orally twice daily. |
| Corticosteroid | DRUG | Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day. |
| Daclizumab | DRUG | Daclizumab 2 milligram (mg) per kilogram (kg) will be administered as intravenous infusion over 15 minute on Day 0 (during the 24 hours preceding renal transplantation) and at a dose of 1 mg/kg on Day14. |
| Mycophenoate Mofetil | DRUG | Mycophenoate mofetil 1 gram (g) (2\*500mg tablets or 4\*250mg capsules) will be given twice daily (daily dose of 2 g) orally for 12 months. |
| Prednisolone | DRUG | Prednisolone 250 mg intravenously on Day 0, followed by 0.5 mg/kg orally daily (maximum 40 mg daily) from Day 1 to Day 7, then 0.25 mg/kg orally daily (maximum 20 mg daily), then dose will be stepwise reduced by 2.5 mg per week to reach to a dose level of 10 mg daily and continued up to 6 months and finally drug will be discontinued after 8 months. |
| Sirolimus | DRUG | Sirolimus tablets will be given orally from week 12 to week 52, starting with loading dose of 10 mg daily for 2 days followed by 6 mg daily to adapt to trough concentrations of 8-15 ng/mL from week 12 to week 39, and 5-10 ng/mL from week 39 to week 52. |
| mycophenolate mofetil (CellCept) | DRUG | 1g bid for 36 weeks |
| placebo | DRUG | po bid for 36 weeks |
| mycophenolate mofetil [CellCept] | DRUG | 1g po bid |
| Mycophenolate Mofetil 2 g/Day | DRUG | Mycophenolate mofetil 500 mg tablets; 4 tablets twice daily for 52 weeks |
| Mycophenolate Mofetil (MMF) 3 g/Day | DRUG | Mycophenolate mofetil 500 mg tablets; 6 tablets twice daily for 52 weeks |
| Neoral | DRUG | Low dose (target trough level 50-100ng/mL) |
| Zenapax | DRUG | 2mg/kg iv first dose, then 1mg/kg every 2 weeks |
| Mycophenolate Mofetil/Mycophenolic Acid | DRUG | MMF/MPA will be administered as per schedule specified in the respective arm. |
| Obinutuzumab | DRUG | Obinutuzumab will be administered as per schedule specified in the respective arm. |
| Prednisone | DRUG | Prednisone will be administered as per schedule specified in the respective arm. |
| Erythropoietin Beta | DRUG | Recombinant human erythropoietin beta at doses of 30,000 IU/week by the subcutaneous route for 6 weeks. |
| antibody induction | DRUG | According to manufacturer recommendation |
| CellCept (mycophenolate mofetil) | DRUG | - |
Inclusion Criteria: * Confirmed diagnosis of PV within the previous 24 months, based on the presence of histological features of acantholysis via skin or mucosal biopsy and one of the following: tissue bound immunoglobulin G (IgG) antibodies by direct immunofluorescence on the surface of affected e...
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CellCept has been studied in MPO-ANCA vasculitis, including microscopic polyangiitis, in a Phase 1 trial. It is a small molecule developed by Roche Holding AG. The trial enrolled 18 participants and has been completed, with no active trials currently listed for this indication.
CellCept is made by Roche Holding AG, which trades under the ticker RHHBY. Roche is the developer associated with the clinical program studying CellCept in MPO-ANCA vasculitis, a condition that includes microscopic polyangiitis.
CellCept is in Phase 1 development for MPO-ANCA vasculitis. One Phase 1 trial has been completed, and no active trials are currently listed for this indication. CellCept is an investigational therapy in this setting and is not described as approved for MPO-ANCA vasculitis.
CellCept has been evaluated in one clinical trial for MPO-ANCA vasculitis: NCT00405860, titled "CellCept in p-ANCA Vasculitis." The Phase 1 trial was conducted in the United States, enrolled 18 participants aged 18 years and older of all sexes, and has been completed.
The CellCept trial NCT00405860 was a Phase 1 study in MPO-ANCA vasculitis and microscopic polyangiitis. It was an uncontrolled study without randomization or double blinding, and it enrolled 18 participants. It did not use biomarker-based patient selection and did not include healthy volunteers.