Pharmacokinetically-driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis

Study Overview
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Brief Summary
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Meta-analyses in adults suggest equivalence of clinical efficacy of intravenous cyclophosphamide and mycophenolate mofetil when dosed based on patient weight or body-surface-area (MMFBSA), as is the current standard for the treatment of proliferative lupus nephritis (LN) treatments in the U.S. Pharmacokinetically-guided precision dosing of MMF (MMFPK) may offer a beneficial modification of the current standard treatment in that MMKPK promises over 30% higher LN response rates than MMFBSA. The objective of the proposed randomized, controlled study is to compare the efficacy and safety of pharmacokinetically-guided precision dosing of MMF (MMFPK) with conventional dosing regimens of MMF (MMFBSA) among children with proliferative LN.

Official Title
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Pharmacokinetically-driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis with proliferative LN based on kidney biopsy done within 4 weeks of enrollment Diagnosis with childhood-onset SLE (cSLE) as per the ACR criteria95, 96 Age 8 - 17 years at the time of enrollment96 Tolerates oral MMF Exclusion Criteria: Perceived or stated inability to adhere to study protocol, Lack of use of highly effective birth control method. Presence of cSLE features that a-priori suggest that the patient benefits from other therapy than that suggested by the study protocol, History of significant kidney disease prior to the diagnosis with cSLE, Need for renal replacement therapy at the time of enrolment, Concurrent therapy with CYC or rituximab.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMF PK<br> | Drug: Mycophenolate Mofetil<br>* At baseline, subjects will be randomized 1:1 to one of two treatment arms: the current standard of clinical care [MMFBSA: 600 mg/m2/dose; max: 3 gram/day] or pharmacokinetically-driven precision dosing [MMFPK: 12-hour target area under the exposure curve of MPA (MPA-AUC0-12) at 60 mg*h/L].<br>|
| Active Comparator: MMF BSA<br> | Drug: Mycophenolate Mofetil<br>* At baseline, subjects will be randomized 1:1 to one of two treatment arms: the current standard of clinical care [MMFBSA: 600 mg/m2/dose; max: 3 gram/day] or pharmacokinetically-driven precision dosing [MMFPK: 12-hour target area under the exposure curve of MPA (MPA-AUC0-12) at 60 mg*h/L].<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal remission | defined as at least PRR (CRR or PRR) | 26 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Renal Remission | CRR | week 26 |