Mycophenolate Mofetil for Pediatric Lupus Nephritis

(PLUMM Trial)

Recruiting at 19 trial locations

Overseen By Cat Clinical Research Coordinator

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: MMF

Must not be taking: Cyclophosphamide, Rituximab, others

Disqualifiers: Severe hepatic, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of two dosing methods of the drug Mycophenolate Mofetil (MMF) for treating proliferative lupus nephritis in young people. The trial compares dosing based on body size with a more personalized approach to determine which is more effective. Children and teens aged 8 to under 21, diagnosed with lupus nephritis through a recent kidney biopsy and already taking MMF, might be suitable candidates. Participants must be able to take MMF tablets, adhere to the study schedule, and have access to a smartphone for the study app. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require stopping certain medications like cyclophosphamide 12 weeks before the trial and rituximab 6 months before. Herbal supplements must be stopped at least 1 week before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mycophenolate mofetil (MMF) is a safe treatment for lupus-related kidney problems in adults and some children. Studies have found that MMF works as well as cyclophosphamide, another common treatment, and is well-tolerated. In a clinical trial with 130 participants, MMF combined with other medications like prednisone and hydroxychloroquine reduced severe lupus flare-ups. This suggests that MMF is generally safe, but monitoring for any side effects during treatment remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pediatric lupus nephritis, which often rely on fixed dosing methods, Mycophenolate Mofetil (MMF) in this trial is being explored with two innovative dosing strategies. The MMFPK arm uses pharmacokinetically-guided precision dosing, which means the treatment is tailored to each child's unique drug metabolism, potentially increasing effectiveness and reducing side effects. Meanwhile, the MMFBSA arm employs dosing based on body surface area, aiming to optimize the drug's impact by considering individual physical differences. Researchers are excited about these approaches because they promise more personalized and possibly more effective treatment options compared to traditional dosing methods.

What evidence suggests that this trial's treatments could be effective for pediatric lupus nephritis?

Research has shown that Mycophenolate Mofetil (MMF) effectively treats lupus nephritis (LN), a kidney issue related to lupus. Studies have found that MMF works as well as or even better than cyclophosphamide, another common treatment for active lupus. In adults and some children, MMF has already proven to be safe and effective. One study found that MMF improved kidney function by about 6% compared to other treatments. In another study, MMF helped up to 71% of patients achieve kidney remission, although results varied depending on the dose. This trial will compare two dosing strategies for MMF: pharmacokinetically-guided precision-dosing and dosing based on body-surface area, to determine which is more effective for pediatric lupus nephritis. ^{1 3 4 6 7}

Who Is on the Research Team?

Hermine I Brunner, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for kids aged 8 to under 18 with a specific kidney condition called proliferative lupus nephritis. They must meet certain criteria for systemic lupus erythematosus, have a recent kidney biopsy confirming the diagnosis, and be able to take mycophenolate mofetil (MMF) tablets.

Inclusion Criteria

I am taking MMF twice daily for lupus nephritis as my doctor prescribed.

I have been on a stable dose of belimumab for at least 3 months.

Your SLEDAI renal domain score is greater than zero.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive blinded treatment with MMFPK or MMFBSA for up to 26 weeks. The primary endpoint, clinical remission of LN, is measured at the end of Part 1.

26 weeks

Regular visits as per protocol

Treatment Part 2

Subjects with partial renal response (PRR) or complete renal responses (CRR) continue treatment in Part 2. Non-responders are considered treatment failures and discontinued.

27 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment. Subjects who discontinue will still participate in study visits at weeks 26 and 53.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mycophenolate Mofetil

Trial Overview

The PLUMM study tests two ways of dosing MMF in children with lupus nephritis: one based on body surface area and another tailored to individual drug levels in the blood. The goal is to see which method is safer and more effective over a year.

How Is the Trial Designed?

Group I: MMFPK Experimental Treatment 1 Intervention

MMF dosed as per pharmacokinetically-guided precision-dosing

Group II: MMFBSA Active Control 1 Intervention

MMF dosed as per body-surface area

Mycophenolate Mofetil is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in United States as Cellcept for:

• Prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in Canada as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Approved in Japan as Cellcept for:

• Prevention of acute organ rejection in kidney, liver, and heart transplant patients
• Treatment of autoimmune diseases such as lupus nephritis and rheumatoid arthritis

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

In a study of 11 children with lupus nephritis treated with mycophenolate mofetil (MMF) for an average of 9.8 months, the treatment showed significant effectiveness in reducing disease activity, as indicated by a marked decrease in SLEDAI scores for 10 out of 11 patients.

MMF was particularly effective in normalizing renal function in patients with membranous glomerulonephritis, while its efficacy was limited in those with proliferative glomerulonephritis, highlighting its potential as a steroid-sparing alternative for certain types of lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. Buratti, S., Szer, IS., Spencer, CH., et al.[2016]

Mycophenolate mofetil, an immunosuppressant used for transplant rejection, shows promise in predicting therapeutic responses in severe lupus nephritis based on initial results from Lertdumrongluk et al.

The study suggests that enteric-coated mycophenolate sodium should not be given to patients who are undergoing therapeutic drug monitoring, indicating a need for careful management of this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of mycophenolic acid: a potential treatment for lupus nephritis. Pawinski, T.[2017]

Mycophenolate mofetil (MMF) is an effective immunosuppressive therapy that inhibits purine synthesis, making it useful for preventing organ rejection in transplants and treating autoimmune conditions like lupus nephritis.

Recent randomized clinical trials have established MMF as a viable alternative to traditional treatments, such as pulse intravenous cyclophosphamide, for managing lupus nephritis in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil for the induction and maintenance treatment of lupus nephritis. González-Rivera, TC., McCune, J.[2016]

In a study of 119 Japanese patients with systemic lupus erythematosus (SLE) treated with mycophenolate mofetil (MMF), the cumulative discontinuation rate was 42.4%, primarily due to adverse events, indicating that while MMF is effective, it can lead to significant side effects.

Patients who experienced adverse events had a lower rate of achieving lupus low disease activity state (35% vs. 64%), and high concentrations of mycophenolate acid were associated with serious complications, such as viral meningitis, highlighting the need for careful monitoring of drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study. Abe, Y., Tada, K., Yamaji, K., et al.[2022]

In a study of five children with lupus nephritis, mycophenolate mofetil (MMF) combined with corticosteroids led to significant improvements, with three patients achieving complete remission of nephrotic syndrome and normalization of renal function during the induction phase.

MMF was well tolerated overall, showing promise as a safer alternative to traditional treatments, although one patient experienced severe complications leading to death from sepsis due to leucopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Interest of mycophenolate mofetil in children with membranous lupus nephritis]. Gargah, T., Goucha-Louzir, R., Lakhoua, MR.[2016]

Mycophenolate mofetil is an effective immunosuppressive drug for renal transplantation, working by inhibiting lymphocyte proliferation through the de novo pathway of purine synthesis.

Recent studies indicate that mycophenolate mofetil may also reduce renal injury in lupus nephritis patients when combined with steroids, but further confirmation through larger randomized-controlled trials is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of systemic lupus erythematosus with mycophenolate mofetil. Adu, D., Cross, J., Jayne, DR.[2017]

Mycophenolate mofetil (MMF) was found to be an effective treatment for juvenile onset severe lupus nephritis, showing significant improvements in urine protein levels, renal function, and antibody levels after 6 months of induction therapy in a study of 12 children.

During the 18 months of maintenance therapy, no patients experienced renal flares, indicating that MMF can safely maintain remission, although some patients did experience major infections, such as herpes zoster and bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in induction and maintenance therapy for juvenile onset severe lupus nephritis]. Kise, T., Yoshimura, H.[2016]

Enteric-coated mycophenolate sodium (EC-MPS) effectively reduced proteinuria and improved renal function in patients with lupus nephritis (LN), with 8 out of 16 patients achieving complete remission.

EC-MPS showed lower efficacy in primary glomerulonephritis (GN) compared to LN, but importantly, it had a low incidence of gastrointestinal side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium. Kitiyakara, C., Ophascharoensuk, V., Changsirikulchai, S., et al.[2019]

In a study of 13 patients with resistant lupus nephritis, mycophenolate mofetil (MMF) was well-tolerated and led to serological improvements in 9 out of 13 patients, while also allowing for a reduction in steroid dosage for 8 out of 10 patients.

MMF significantly slowed the decline of renal function in these patients, suggesting it could be an effective treatment option for those with long-standing lupus nephritis, although further controlled clinical trials are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of MMF in lupus nephritis: a pilot study. Kingdon, EJ., McLean, AG., Psimenou, E., et al.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28182833/

Comparative Effectiveness of Mycophenolate Mofetil for the ...

Overall, MMF was superior to other therapies, with a relative effect estimate for MMF of 1.06, i.e., 6% better estimated GFR on average (95% confidence interval ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11258879/

Efficacy and Safety of Pharmacokinetically-Driven Dosing of ...

The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children.

3.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT05538208

Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) ...

The study goal is to determine the safety and efficacy of MMFPK compared to MMFBSA for the treatment of proliferative LN in subjects 8 to <21 years.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1684118223001536

Comparison of mycophenolic acid with cyclophosphamide ...

The result showed that renal remission was achieved in 71% of the low-dose group and in 54% of the high-dose group (not statistically significant). A web-based ...

5.

journals.lww.com

journals.lww.com/jasn/fulltext/9900/mycophenolate_mofetil_versus_cyclophosphamide_for.764.aspx

Mycophenolate Mofetil versus Cyclophosphamide for Initial...

Several previous studies on lupus nephritis have shown that MMF is as effective as intravenous cyclophosphamide in treating active lupus ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39035447/

Efficacy and Safety of Pharmacokinetically-Driven Dosing of ...

Abstract · Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children.

7.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2823522

Mycophenolate Mofetil and New-Onset Systemic Lupus ...

This randomized clinical trial of 130 participants found that MMF in addition to oral prednisone and hydroxychloroquine sulfate decreased severe flares.