Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis

A Randomized Open-label Study of Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis

A randomized open-label study of fixed-dose versus concentration-controlled mycophenolate mofetil for treatment of active lupus nephritis.

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Mycophenolate Mofetil

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Please Select
    • Bangkok, Please Select, Thailand, 10330
      • King Chulalongkorn Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-65 year
• Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE

• Active lupus nephritis (both new and flare patients can be included) defined as:

  • Within 16 weeks of randomization, had Biopsy-proven ISN class III or IV [exclude III(c), IV-S(c) and IV-G(c). Patients are permitted to have co-existing class V and
  • At screening day, has urine protein creatinine ratio (UPCR) or 24-hour urinary protein ≥ 1.0 g/g or g/day

Exclusion Criteria:

• Pregnancy or breast feeding
• Child-bearing age women who refuse to use effective birth-control
• Poor compliance
• Estimated-GFR < 20 mL/min/1.73 m2
• Crescentic glomeruli more than 30 percent
• Severe extra-renal involvement of SLE
• History of severe allergic reactions or adverse effects to MMF
• Uncontrolled concomitant disease
• Known active, clinically significant infection of any kind
• History of serious recurrent or chronic infection
• History of malignancy (except basal cell carcinoma, squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been excised and cured)
• Concomitant conditions which has required treatment with systemic corticosteroid (excluding topical or inhaled steroids) at any time in the 52 weeks prior to screening
• Treatment with more than 1 g cyclophosphamide within the past 24 weeks
• Receipt more than 3 g of IV pulse methylprednisolone within the past 12 weeks
• Receipt prednisolone more than 30 mg/day for longer than 30 days within the past 12 weeks
• Treatment with MMF at ≥ 1.5 g/day for over 4 weeks within the past 12 weeks
• On treatment with Tacrolimus or Cyclosporine on the day of screening
• Treatment with any biologic B-cell depleting therapy (e.g. anti CD-20, anti CD 22) within 52 weeks

• Receiving concomitant medication interfering PK of MPA

  • Cholestyramine
  • Rifampin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: FD arm; MMF will be prescribed at a starting dose of 1.5 g/day and increased to 2 g/day at week 4 (if body weight ≥ 45 kg) and continue the same dose until week 24. After week 24, MMF will be lowered to 1.5 g/day.	Drug: Mycophenolate Mofetil; Description Each capsule contains Mycophenolate mofetil 250 mg. Presentation / Packing Cap 250 mg (white to off white powder, light blue/peach hard gelatin, imprinting with "MMF" on cap and "250" on body) x 10 x 10's. Storage Store below 30 degree Celcius.
Active Comparator: CC Arm; MMF will be prescribed at a starting dose of 1.5 g/day. MPA-C0 (trough) level will be measured weekly and MMF dose will be increased by 500 mg/day every week until the MPA-C0 level ≥ 3 mg/L or the MMF dosage is 3000 mg/day. After achieving the targeted MPA-C0 level, the MMF dose adjustment will be allowed only if the MPA-C0 levels are lower than 3 mg/L for two consecutive monitoring visits. After week 12, MMF will be maintained at the same dose until week 48	Drug: Mycophenolate Mofetil; Description Each capsule contains Mycophenolate mofetil 250 mg. Presentation / Packing Cap 250 mg (white to off white powder, light blue/peach hard gelatin, imprinting with "MMF" on cap and "250" on body) x 10 x 10's. Storage Store below 30 degree Celcius.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate at 48 week of therapy	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	48 weeks
Mycophenolic acid trough levels	48 weeks
MPA-area under the curve (AUC) 0-4 hour at 12 week	12 weeks
C3 levels	48 weeks
Urine IP-10 levels	48 weeks
Anti-dsDNA	48 weeks
Relapse free survival at 96, 144 and 240 week	96, 144 and 240 weeks
eGFR at 96, 144 and 240 week	96, 144 and 240 weeks
Progression to CKD stage 3 or more at 96, 144 and 240 week	96, 144 and 240 weeks
End stage renal disease at 96, 144 and 240 week	96, 144 and 240 weeks

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: Berlin Pharmaceutical Industry

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2019
• Primary Completion (Actual): January 30, 2020
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: FDCC lupus

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No