The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study
- Registration Number
- NCT05538208
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 105
Not provided
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Perceived or stated inability to adhere to the study protocol;
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Hypersensitivity to MMF or any component of the drug product;
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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.
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History of other kidney disease besides LN or prior to the diagnosis of SLE;
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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.
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Infections:
- Untreated latent or active tuberculosis (TB);
- Chronic infections requiring treatment;
- A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
- Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
- Any treated infections within 2 weeks of Baseline visit;
- History of infected joint prosthesis with prosthesis still in situ;
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Blood dyscrasias, including:
- Hemoglobin <8.5 g/dL or Hematocrit <22%;
- White Blood Cell count <2.6 x 109/L;
- Neutrophil count <1.2 x 109/L;
- Platelet count <100 x 109/L;
- Lymphocyte count <0.5 x 109/L.
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- Estimated glomerular filtration rate [GFR] <40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal;
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Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
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History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus [EBV] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
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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;
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Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
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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).
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Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
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Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
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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.
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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;
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MMFBSA Mycophenolate Mofetil MMF dosed as per body-surface area MMFPK Mycophenolate Mofetil MMF dosed as per pharmacokinetically-guided precision-dosing
- Primary Outcome Measures
Name Time Method To compare the efficacy of MMFPK therapy to the efficacy of MMFBSA therapy 26 week the percentage of subjects achieving at least partial remission of LN (PRR) as per the adapted ACR/EULAR Criteria at Week 26
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
University of California, San Francisco
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Emory Children's Center
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Medicine- Comer Children's
🇺🇸Chicago, Illinois, United States
Washington University in St. Louis School of Medicine
🇺🇸St. Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Children's Hospital at Montefiore
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Baylor College of Medicine Pediatric Immunology Allergy Rheumatology
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital/University of Washington
🇺🇸Seattle, Washington, United States
Children's Wisconsin/Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States