Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Mycophenolate Mofetil
Mycophenolate Mofetil/Mycophenolic Acid · 3 trials · 1 indication
A participant had a CRR if they met the following 3 criteria: (1) Normalization of serum creatinine (SC) as evidenced by a SC level ≤ the upper limit of the normal range of central laboratory values or a SC level ≤ 15% greater than Baseline, if Baseline SC was within the normal range of the central laboratory values; (2) Inactive urinary sediment (as evidenced by \< 5 red blood cells/high-power field (RBCs/HPF) and absence of red cell casts; (3) Urinary protein (UP) to creatinine ratio (CR) \< 0.5. A participant had a PRR if they met the following 3 criteria: (1) A SC level ≤ 15% above Baseline; (2) RBCs/HPF ≤ 50% above Baseline and no RBC casts; (3) 50% improvement in the UP to CR, with 1 of the following conditions met: If the Baseline UP to CR was ≤ 3.0, then a UP to CR of \< 1.0 or if the Baseline UP to CR was \> 3.0, then a UP to CR of ≤ 3.0. A participant had a NRR if they did not achieve either a CRR or PRR.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Rituximab | EXPERIMENTAL | Participants received rituximab 1000 mg intravenously (IV) on Days 1, 15, 168, and 182. They also received mycophenolate mofetil, methylprednisolone, diphenhydramine, acetaminophen, and prednisone; see the Detailed Description for details. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo intravenously (IV) on Days 1, 15, 168, and 182. They also received mycophenolate mofetil, methylprednisolone, diphenhydramine, acetaminophen, and prednisone; see the Detailed Description for details. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Rituximab | DRUG | Rituximab was provided as a sterile solution for injection. |
| Placebo | DRUG | Placebo was provided as a sterile solution for injection. |
| Mycophenolate mofetil | DRUG | - |
| Methylprednisolone | DRUG | - |
| Diphenhydramine | DRUG | - |
| Acetaminophen | DRUG | - |
| Prednisone | DRUG | - |
| Mycophenolate mofetil (MMF) | DRUG | Supplied as 500 mg tablets taken orally twice a day (BID). Dose specific for each arm. Dosing started at 500 mg BID for the first week, increasing by 500 mg in subsequent weeks until the final target dose was reached. |
| 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. |
| 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. |
Inclusion Criteria: * Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria. * Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), with either active or active/ch...
Mycophenolate Mofetil is an immunosuppressant small molecule being studied for use in Pemphigus Vulgaris, Myelodysplastic Syndromes, Chronic Kidney Failure, Heart Transplantation, and Lung Transplantation. It is developed by Roche Holding AG (RHHBY) and is currently in Phase 3 clinical development for these indications.
Mycophenolate Mofetil is an immunosuppressant that inhibits inosine monophosphate dehydrogenase, an enzyme crucial for the de novo synthesis of guanine nucleotides in lymphocytes. By blocking this enzyme, it selectively suppresses T and B cell proliferation, reducing the immune response that contributes to autoimmune and transplant-related conditions.
Mycophenolate Mofetil is developed by Roche Holding AG, a Swiss multinational healthcare company traded on the OTC market under the ticker RHHBY. Roche is conducting clinical trials to evaluate the drug's efficacy and safety in various conditions, including heart transplantation and myelodysplastic syndromes.
Mycophenolate Mofetil is in Phase 3 clinical development. It has completed three trials, including two Phase 3 studies and one Phase 2 study, with a total enrollment of 640 participants. The drug is investigational and not yet approved for the studied indications.
Mycophenolate Mofetil has been studied in three completed trials: NCT00282347 (Phase 3, Lupus Nephritis, 144 participants), NCT00551291 (Phase 2, Myelodysplastic Syndromes, 10 participants), and NCT02091414 (Phase 3, Heart Transplantation, 36 participants). All trials are completed with no active studies ongoing.
Yes, Mycophenolate Mofetil is the same as CellCept, a brand name used in clinical trials. In the study NCT00551291, the drug is referred to as CellCept, and in NCT02091414, it is also called CellCept. Both names refer to the same immunosuppressant compound developed by Roche.