The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study

NCT ID: NCT05538208

Last Updated: 2025-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-07

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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Subjects will be randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary endpoint, clinical remission of LN, is measured at the end of Part 1 at week 26. Subjects in the MMFBSA arm who have only partial renal response (PRR) at the end of Part 1 will newly receive MMFPK upon entering Part 2 of the study (week 26 - 53). Subjects with complete renal responses (CRR) at the end of Part 1 will continue the same dosing regimen of MMF (MMFBSA or MMFPK) in Part 2 as was given in Part 1 of the study. Subjects in the MMFPK arm with PRR at the end of Part 1 will enter Part 2 and continue in the MMFPK arm.

Subjects who are LN non-responders by the end of Part 1 at week 26 will be considered treatment failures and discontinued from the study intervention. All subjects who are discontinued from the study intervention for reasons of efficacy or safety will receive LN treatment and monitoring as per the treating physician's decision. However, these subjects will be asked to participate in study visits at weeks 26 and 53/End of Study.

Conditions

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Lupus Nephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eligible patients enrolled in the study will be randomized (1:1) at baseline to the 53-week double-blind, active comparator 2-part study to receive either MMFPK or MMFBSA. Subjects who are partial renal responders (PRR) to MMFBSA at week 26, will cross over to the MMFPK arm. Complete renal responders (CRR) at week 26 in MMFBSA arm will continue to be treated with MMFBSA. Subjects with at least a PRR (or even CRR) in the MMFPK arm at week 26 will remain in the MMFPK arm and continue to receive MMF dosage targeting MPA-AUC0-12 \> 60-70 mg\*h/l. Subjects whose LN fails to respond to therapy by week 26 will be discontinued from the study interventions to receive LN treatment as per their local physician's decision. Subjects who experience a single episode of a LN flare during Part 1 of the study or fulfill other criteria for discontinuation from the study intervention, will also receive LN treatment as per their local physician's decision.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
During this double-blinded study, the Sponsor, subject, and investigator site staff will all be blinded to the subject's treatment assignment.

Study Groups

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MMFBSA

MMF dosed as per body-surface area

Group Type ACTIVE_COMPARATOR

Mycophenolate Mofetil

Intervention Type DRUG

MMF dosed 600mg/m2 body surface area per dose about every 12 hours

MMFPK

MMF dosed as per pharmacokinetically-guided precision-dosing

Group Type EXPERIMENTAL

Mycophenolate Mofetil

Intervention Type DRUG

MMF dosed twice daily to achieve an area under the concentration-time curve (AUC 0-12h) of MPA \>=60-70 mg\*h/L

Interventions

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Mycophenolate Mofetil

MMF dosed 600mg/m2 body surface area per dose about every 12 hours

Intervention Type DRUG

Mycophenolate Mofetil

MMF dosed twice daily to achieve an area under the concentration-time curve (AUC 0-12h) of MPA \>=60-70 mg\*h/L

Intervention Type DRUG

Other Intervention Names

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MMF dosed per body surface area MMF dosed phrmacokinetically

Eligibility Criteria

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Inclusion Criteria

1. Male or female aged 8 to \< 21 years;
2. Must meet Classification Criteria for SLE as per the criteria of the American College of Rheumatology (ACR)/ European League Against Rheumatism
3. Diagnosed with proliferative LN as per the International Society of Nephrology/Renal Pathology Society4 based on kidney biopsy done within 90 days prior to enrollment into the study;

Subjects may have been previously diagnosed with LN. For study inclusion, the kidney biopsy must be interpreted as one of the following classes: Class 3, Class 3/5, Class 4, or Class 4/5.
4. Treatment of LN with twice daily MMF as per the decision of the treating physician.

The subject will have taken MMF as prescribed by their treating physician for a minimum of 4 days (or 8 doses).
5. Subject tolerates MMF as per the treating physician's opinion;
6. Able to swallow MMF tablets and capsules;
7. If subject is treated with belimumab, must be IV or SQ;
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
9. Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/ parent(s)/legal guardian has been informed of all pertinent aspects of the study.
10. Parent or legal guardian must have a smart phone available and able to support the PLUMM smart phone application.
11. Must be able to complete study questionnaires in English or Spanish.

Exclusion Criteria

1. Perceived or stated inability to adhere to the study protocol;
2. Hypersensitivity to MMF or any component of the drug product;
3. Presence of features (from SLE or other chronic disease) that a-priori suggest that the subject benefits from other therapies than that suggested or allowable by the study protocol; These disease features include but are not limited to severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
4. History of other kidney disease besides LN or prior to the diagnosis of SLE;
5. Need for renal replacement therapy within 2 weeks from Baseline Subjects can have required short-term renal replacement therapy prior to Baseline, for example due to preceding acute kidney injury.
6. Infections:

1. Untreated latent or active tuberculosis (TB);
2. Chronic infections requiring treatment;
3. A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
4. Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
5. Any treated infections within 2 weeks of Baseline visit;
6. History of infected joint prosthesis with prosthesis still in situ;
7. Blood dyscrasias, including:

1. Hemoglobin \<8.5 g/dL or Hematocrit \<22%;
2. White Blood Cell count \<2.6 x 109/L;
3. Neutrophil count \<1.2 x 109/L;
4. Platelet count \<100 x 109/L;
5. Lymphocyte count \<0.5 x 109/L.
8. 8\) Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the upper limit of normal;
10. Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
11. History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
12. Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ;
13. Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
14. Herbal supplements with pharmaceutical properties must be discontinued at least 1week prior to Baseline visit, unless there are sufficient data available regarding the duration of an herbal medication's pharmacokinetic and pharmacodynamic effects to allow a shorter or longer washout to be specified (e.g., 5 half-lives).
15. Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
16. Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
17. Participation in other studies involving investigational drug(s) within 4 weeks or 5 half-lives (whichever is longer) prior to Baseline visit and/or during study participation; Exposure to investigational biologics should be discussed with the Sponsor.
18. Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use two highly effective methods of contraception or are abstinent for the duration of the study;
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
Minimum Eligible Age

8 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

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

NIH

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Hermine Brunner, MD

Division Director Rheumatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hermine I Brunner, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Emory Children's Center

Atlanta, Georgia, United States

Site Status RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

University of Chicago Medicine- Comer Children's

Chicago, Illinois, United States

Site Status RECRUITING

Washington University in St. Louis School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Hospital for Special Surgery

New York, New York, United States

Site Status RECRUITING

Children's Hospital at Montefiore

New York, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Akron Children's Hospital

Akron, Ohio, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

Baylor College of Medicine Pediatric Immunology Allergy Rheumatology

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Seattle Children's Hospital/University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Children's Wisconsin/Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Angela Sr CRC

Role: CONTACT

513-803-2118

Cat Clinical Research Coordinator

Role: CONTACT

513-636-7299

Facility Contacts

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Zilan Clinical Research Coordinator

Role: primary

(415) 353-1301

Ryan Senior Clinical Research Coordinator

Role: primary

303-913-5450

Heather Clinical Research Coordinator

Role: primary

404-712-8037

Maria Amoruso

Role: primary

312-227-6276

Melissa Director Pediatric Clinical Trials Office

Role: primary

773-702-2927

Joseph Clinical Research Coordinator

Role: primary

314-747-1349

Amanda Nowakowski

Role: primary

551-996-3114

Julia Klauss

Role: primary

212-774-2703

Lisbel Guzman

Role: primary

Carolina Pastrana-Medina

Role: primary

Jessica Clinical Research Nurse

Role: primary

330-603-2234

Angela

Role: primary

5133384396

Erica Clinical Research Specialist

Role: primary

216-286-7453

Cindy Clinical Research Nurse

Role: primary

614-722-0504

Susannnah Program Coordinator

Role: primary

843-792-8317

Monica Guevara

Role: primary

832-824-1206

Suzy Clinical Research Coordinator

Role: primary

801-585-5067

Megan Clinical Research Supervisor

Role: primary

206-200-3502

Nathan Clinical Research Coordinator

Role: primary

414-266-5662

Other Identifiers

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1R01AR079124-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ML42264

Identifier Type: -

Identifier Source: org_study_id

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