Mycophenolate Mofetil for Pediatric Lupus Nephritis

(PLUMM Trial)

Recruiting at 18 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

Trial Summary

What is the purpose of this trial?

The study is a 1-year 2-part double-blinded placebo controlled 2-arm clinical trial. Treatment arms are (1) MMF dosed as per body-surface area (MMFBSA; 600mg/m2 body surface area per dose about every 12 hours) and (2) pharmacokinetically-guided precision-dosing of MMF (MMFPK; MMF dosed twice daily to achieve an area under the concentration-time curve (AUC0-12h) of MPA \>60-70 mg\*h/L. 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.

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.

What data supports the effectiveness of the drug Mycophenolate Mofetil for treating pediatric lupus nephritis?

Research shows that Mycophenolate Mofetil (MMF) is effective in treating lupus nephritis in children, with many patients achieving remission and improved kidney function. It is considered a viable alternative to other treatments, with studies indicating it can reduce the need for steroids and improve symptoms in patients with resistant lupus nephritis. ^{1 2 3 4 5}

Is Mycophenolate Mofetil safe for children with lupus nephritis?

Mycophenolate Mofetil (also known as CellCept or Myfortic) has been used in children with lupus nephritis and is generally well tolerated, though one study reported a serious infection in a patient. It is important to monitor for side effects, especially infections, as it can affect the immune system. ^{1 2 4 6 7}

How is the drug Mycophenolate Mofetil unique in treating pediatric lupus nephritis?

Mycophenolate Mofetil (MMF) is unique because it is an immunosuppressive drug that specifically inhibits lymphocyte proliferation, which helps reduce kidney inflammation in lupus nephritis. Unlike traditional treatments like corticosteroids and cyclophosphamide, MMF is often better tolerated and can be used alone during the maintenance phase, potentially reducing long-term side effects. ^{2 4 7 8 9}

Research Team

Hermine I Brunner, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 (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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil for the induction and maintenance treatment of lupus nephritis. [2016]

2. Canada pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. [2016]

3. Japan pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in induction and maintenance therapy for juvenile onset severe lupus nephritis]. [2016]

4. France pubmed.ncbi.nlm.nih.gov

[Interest of mycophenolate mofetil in children with membranous lupus nephritis]. [2016]

5. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of MMF in lupus nephritis: a pilot study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium. [2019]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Treatment of systemic lupus erythematosus with mycophenolate mofetil. [2017]