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

Primary Purpose

Lupus Nephritis

Status
Terminated
Phase
Phase 4
Locations
Thailand
Study Type
Interventional
Intervention
Mycophenolate Mofetil
Sponsored by
Chulalongkorn University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • King Chulalongkorn Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

FD arm

CC Arm

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Response rate at 48 week of therapy

Secondary Outcome Measures

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

Full Information

First Posted
April 1, 2019
Last Updated
January 27, 2021
Sponsor
Chulalongkorn University
Collaborators
Berlin Pharmaceutical Industry
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1. Study Identification

Unique Protocol Identification Number
NCT03920059
Brief Title
Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis
Official Title
A Randomized Open-label Study of Fixed-dose Versus Concentration-controlled Mycophenolate Mofetil for the Treatment of Active Lupus Nephritis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Slow recruitment rate
Study Start Date
August 20, 2019 (Actual)
Primary Completion Date
January 30, 2020 (Actual)
Study Completion Date
January 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chulalongkorn University
Collaborators
Berlin Pharmaceutical Industry

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FD arm
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
CC Arm
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response rate at 48 week of therapy
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Adverse events
Time Frame
48 weeks
Title
Mycophenolic acid trough levels
Time Frame
48 weeks
Title
MPA-area under the curve (AUC) 0-4 hour at 12 week
Time Frame
12 weeks
Title
C3 levels
Time Frame
48 weeks
Title
Urine IP-10 levels
Time Frame
48 weeks
Title
Anti-dsDNA
Time Frame
48 weeks
Title
Relapse free survival at 96, 144 and 240 week
Time Frame
96, 144 and 240 weeks
Title
eGFR at 96, 144 and 240 week
Time Frame
96, 144 and 240 weeks
Title
Progression to CKD stage 3 or more at 96, 144 and 240 week
Time Frame
96, 144 and 240 weeks
Title
End stage renal disease at 96, 144 and 240 week
Time Frame
96, 144 and 240 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
King Chulalongkorn Memorial Hospital
City
Bangkok
State/Province
Please Select
ZIP/Postal Code
10330
Country
Thailand

12. IPD Sharing Statement

Learn more about this trial

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

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