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Label indication Sirolimus is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants: • Patients at low- to moderate-immunologic risk: Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2–4 months after transplantation ( 1.1 ).
Also known as Sirolimus (RAPAMUNE), Rapamycin, Rapamune
Sirolimus · 11 trials · 9 indications
The diagnosis of acute rejection required a kidney biopsy. Biopsies were assessed using the Banff criteria, standardized diagnostic categories based on histological assessments (e.g., cell types and distributions).
Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance rate was calculated using the Nankivell formula. Normal values for healthy, young males are in the range of 100-135 ml/min and for females 90-125 ml/min. A low creatinine clearance indicates poor kidney function.
Nankivell GFR: patients with baseline GFR of 20.0 to 40.0 mL/min and patients with baseline GFR of greater than 40.0 mL/min. GFR is an index of kidney function. A higher value means better kidney function.
Change over six months in cognitive functioning in Sturge-Weber syndrome is the primary outcome measure. This outcome will be assessed using the NIH Toolbox Cognitive Battery, a panel of testing which includes the following measures: * the Flanker Inhibitory Control and Attention Test (executive function and attention) * the Dimensional Change Card Sort Test (executive function) * Picture Sequence Memory Test (episodic memory) * Oral Reasoning Recognition Test and Picture Vocabulary Test (language skills) * Pattern Comparison Processing Speed Test (processing speed) * List Sorting Working Memory Test (working memory) * 9-hole Peg Test (dexterity) * Grip Strength Test (grip strength) and * Patient-Reported Outcomes Measurement Information System (PROMIS) (self-report emotional functioning). These scores are rescaled to T scores (mean = 50, standard deviation (SD) = 10), referenced against the US population. Higher scores indicate better outcome. T scores only were analyzed.
DF, also known as peak to trough fluctuation (PTF) (calculated as \[Cmax minus Ctrough\] divided by Cave), is a unit-less ratio of the Cmax to Ctrough decrease expressed as a fraction of the average concentration during a dosing interval.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
| Arm | Type | Description |
|---|---|---|
| A | ACTIVE_COMPARATOR | - |
| B | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | Sirolimus + Daclizumab + Mycophenolate + Corticosteroids |
| 2 | ACTIVE_COMPARATOR | Cyclosporine + Mycophenolate + Corticosteroids |
| Sirolimus | EXPERIMENTAL | All subjects will receive the sirolimus oral solution to be taken at home twice daily and will be treated on an outpatient basis. The drug will be taken for six months. |
| Name | Type | Description |
|---|---|---|
| Sirolimus (Rapamune®) | DRUG | (1mg tablets): Initial loading dose of 6mg/day, followed by maintenance dose of 2mg/day, which was adjusted to specified trough level. |
| Cyclosporine | DRUG | Arm 1= Rapamune+ low dose Cyclosporine+steroids "Arm 2= 1° day rapamune 15 mg/die + steroids 2°-7° day Rapamune 5mg/die + steroids In both arms, Cylcoporine is stopped " |
| Steroids | DRUG | Arm 1= Rapamune+ low dose Cyclosporine+steroids "Arm 2= 1° day rapamune 15 mg/die + steroids 2°-7° day Rapamune 5mg/die + steroids In both arms, Cylcoporine is stopped " |
| Rapamune (Sirolimus) | DRUG | Arm 1= Rapamune+ low dose Cyclosporine+steroids "Arm 2= 1° day rapamune 15 mg/die + steroids 2°-7° day Rapamune 5mg/die + steroids In both arms, Cylcoporine is stopped " |
| sirolimus | DRUG | 15 mg loading dose, followed by 5 mg/day to achieve target trough levels of 10-15 ng/mL at months 1-6, then 8-12 ng/mL at months 7-12 |
| mycophenolate mofetil | DRUG | 1 g twice daily; may be reduced to 750 mg BID for adverse events, or to 500 mg BID for persisting adverse events |
| corticosteroids | DRUG | As per center practice. By day 8 prednisolone tapered to 20 mg/day; by day 30 to 15 mg/day; by day 60 to 10 mg/day; after 4 to 6 months to 5-7.5 mg/day |
| daclizumab | DRUG | IV: 1 mg/kg to a maximum of 100 mg/dose. 5 doses at 2, 4, 6, and 8 weeks after transplantation |
| Rapamune | DRUG | - |
| tacrolimus | DRUG | - |
| Cyclosporine A | DRUG | - |
| Rapamune® | DRUG | - |
| Sirolimus (RAPAMUNE) | DRUG | - |
| Rapamune® (Sirolimus) | DRUG | - |
Inclusion Criteria: 1. Age greater than or equal to 13 years of age. 2. End-stage renal disease in patients scheduled to receive a primary renal allograft from a cadaveric donor, a living-unrelated donor, or from a living-related (excluding 0 antigen mismatch) donor. A mismatch donor is defined as ...
Top 4 of 6 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Sanofi SA Sponsored ADR | SNY | 5 | PHASE3 | Belumosudil |
| Incyte Corporation | INCY | 10 | PHASE3 | INCA034176, Ruxolitinib, Axatilimab |
| Johnson & Johnson | JNJ | 1 | PHASE3 | Ibrutinib |
| Syndax Pharmaceuticals Inc | SNDX | 1 | PHASE2 | Axatilimab |
Sirolimus is a small molecule immunosuppressant developed by Pfizer, Inc. (PFE). It is studied in immunology for conditions including graft versus host disease, renal transplant and renal transplantation, transplant rejection, and Sturge-Weber syndrome. It is also known by the brand name Rapamune.
Sirolimus is used in renal transplantation to prevent transplant rejection. It is studied as part of maintenance immunosuppressive regimens in kidney transplant recipients, including active-controlled Phase 3 trials evaluating its use alongside other immunosuppressive agents such as cyclosporine.
Sirolimus targets FKBP1A and acts as an inhibitor. By binding FKBP1A, it interferes with signaling pathways involved in immune cell activation and proliferation, which underlies its immunosuppressive activity in transplant settings and in conditions such as graft versus host disease.
Sirolimus is developed by Pfizer, Inc., which trades under the ticker PFE. The drug is marketed under the brand name Rapamune, and Pfizer has sponsored clinical studies of sirolimus maintenance regimens in renal transplant recipients.
Sirolimus has been evaluated in Phase 3 clinical development. Completed trials include Phase 3 studies in renal transplant and renal transplantation, along with Phase 2 and Phase 1 studies. It is also known as Rapamune.
Sirolimus has been studied in completed trials including NCT03047980, a Phase 2 trial of sirolimus for cognitive impairment in Sturge-Weber syndrome; NCT01236378, a Phase 1 pharmacokinetics study in stable renal transplant recipients; NCT00478608, a Phase 3 Rapamune maintenance regimen study; and NCT00428064, a Phase 3 study of sirolimus and cyclosporine in kidney transplant recipients.