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

NCT05101447 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: PRUNE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• renal remission

  defined as at least PRR (CRR or PRR)

  26 week

Secondary Outcomes (1)

• Complete Renal Remission

  week 26

Study Arms (2)

MMF PK

EXPERIMENTAL

Drug: Mycophenolate Mofetil

MMF BSA

ACTIVE COMPARATOR

Drug: Mycophenolate Mofetil

Interventions

Mycophenolate Mofetil DRUG

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 \[MMFPK: 12-hour target area under the exposure curve of MPA (MPA-AUC0-12) at 60 mg\*h/L\].

MMF BSA; MMF PK

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Rheumatology

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: November 1, 2021
• Study Start: July 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: July 1, 2024
• Last Updated: August 30, 2023

Record last verified: 2023-08