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Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

Primary Purpose

Lupus Nephritis

Status

Recruiting

Phase

Phase 4

Locations

Hong Kong

Study Type

Interventional

Intervention

Tacrolimus

Mycophenolate mofetil

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Nephritis, mycophenolate mofetil, tacrolimus

Eligibility Criteria

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

Inclusion Criteria:

Biopsy-proven LN Class III/IV±V (ISN/RPS 2003), with biopsy performed within 12 weeks of randomization.
Positive anti-dsDNA.
Active LN with proteinuria (urine protein/creatinine ratio >1.0 or 24-hr urine protein >1.0 g at baseline), with or without hematuria.
Both 'incident' (i.e. new) patients and 'flare' patients can be included.

Exclusion Criteria:

Renal disease unrelated to SLE (e.g. diabetes mellitus, other glomerular or tubulointerstitial disease, renovascular disease), or transplanted kidney.
Estimated glomerular filtration rate (eGFR by MDRD) ≤20 mL/min per 1.73 m2 or serum creatinine >300 micromol/L (3.39 mg/dL) at screening.
Renal biopsy showing cellular or fibrocellular crescent in more than 25% of glomeruli.
CNS or other severe organ manifestation of lupus that necessitate aggressive immunosuppressive therapy on its own.
Co-morbidities that require corticosteroid therapy (e.g. asthma, inflammatory bowel disease).
Treatment with prednisolone (or prednisone, or equivalent) at >20 mg/D for over 4 weeks within the past 3 months.
Treatment with MMF at >1.5 g/D for over 4 weeks within the past 3 months.
Known hypersensitivity or intolerability to prednisolone (or prednisone, or equivalent), TAC, or MMF at a dose of 1.25 g or below per day.
Subjects who are already on treatment with TAC, cyclosporine or any other calcineurin inhibitor for over 4 weeks within the past 12 months.
Treatment with cyclophosphamide, leflunomide, or methotrexate for over 2 weeks, or use of biological agent(s) regardless of duration, within the past 6 months (Note: prior use of azathioprine, mizoribine, intravenous immunoglobulins and anti-malarials is allowed).
Uncontrolled hypertension with systolic BP >160 mmHg or diastolic BP >95 mmHg.
Women who are pregnant or breastfeeding.
Women with childbearing potential or their male partners, who refuse to use an effective birth control method

Sites / Locations

The University of Hong KongRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tacrolimus

Mycophenolate Mofetil

Arm Description

route: oral duration: 96 weeks

Outcomes

Primary Outcome Measures

Efficacy of combined corticosteroids and TAC compared to combined corticosteroids and MMF in achieving sustained renal response (RR) in patients with active lupus nephritis [Class III/IV±V (LN)]

Sustained RR defined as satisfying all of the following criteria: proteinuria improved by >50% compared with baseline 24-hr urine protein <1 g serum creatinine not higher than 15% above baseline level no occurrence of disease flare, defined as receiving 'rescue' increase of immunosuppressive therapy with any one of the following - requiring increase of prednisolone (or prednisone, or equivalent) dose to above 15 mg/D for 4 weeks or longer, change of originally assigned immunosuppressive agent, or addition of immunosuppressive medications prohibited in protocol

Secondary Outcome Measures

Full Information

NCT ID

NCT02630628

First Posted

December 5, 2015

Last Updated

May 16, 2022

Sponsor

The University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT02630628

Brief Title

Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

Official Title

A Randomized Open-label Study to Evaluate the Efficacy and Safety of Tacrolimus and Corticosteroids in Comparison With Mycophenolate Mofetil and Corticosteroids in Subjects With Class III/IV±V Lupus Nephritis

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 5, 2015 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Hong Kong

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Prospective, randomized, parallel-group controlled, open-label, international (Asian) multicenter, comparison of corticosteroids combined with TAC and corticosteroids combined with MMF.

Detailed Description

There is accumulating evidence that tacrolimus (TAC) could serve as an effective medication for the treatment of lupus nephritis (LN). TAC is a calcineurin inhibitor, which is a key component in first-line combination immunosuppressive regimens after kidney transplantation, based on its proven efficacy in the prevention and treatment of allograft rejection and acceptable tolerability profile. Although it primarily targets T lymphocyte activation, its immunosuppressive actions encompass multiple immune response pathways due to the complex interactions between different cellular and soluble immune mediators. Moreover, the effect of calcineurin inhibitors on podocyte morphology and function, independent of their immunosuppressive effect, has translated into therapeutic efficacy in the treatment of proteinuric glomerular diseases such as membranous nephropathy and focal segmental glomerulosclerosis. Recent data from short-term studies showed that combination immunosuppressive regimens that included TAC and corticosteroids with or without mycophenolate mofetil (MMF) appeared at least as effective as other standard-of-care treatments for Class III/IV±V LN, and the inclusion of TAC might lead to more effective suppression of proteinuria. There is also preliminary data on its favorable tolerability when used as long-term maintenance treatment. This study aims to examine the role of TAC combined with corticosteroids, in comparison with the most commonly used standard-of-care treatment MMF plus corticosteroids, in the management of lupus nephritis.

6. Conditions and Keywords

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

Lupus Nephritis

Keywords

Lupus Nephritis, mycophenolate mofetil, tacrolimus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tacrolimus

Arm Type

Experimental

Arm Description

route: oral duration: 96 weeks

Arm Title

Mycophenolate Mofetil

Arm Type

Active Comparator

Arm Description

route: oral duration: 96 weeks

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

Prograf

Intervention Description

Dosage: start at 2mg twice a day, then taper as per protocol

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

Cellcept

Intervention Description

Dosage: start at 1g twice a day, then taper as per protocol

Primary Outcome Measure Information:

Title

Efficacy of combined corticosteroids and TAC compared to combined corticosteroids and MMF in achieving sustained renal response (RR) in patients with active lupus nephritis [Class III/IV±V (LN)]

Description

Time Frame

96 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Biopsy-proven LN Class III/IV±V (ISN/RPS 2003), with biopsy performed within 12 weeks of randomization. Positive anti-dsDNA. Active LN with proteinuria (urine protein/creatinine ratio >1.0 or 24-hr urine protein >1.0 g at baseline), with or without hematuria. Both 'incident' (i.e. new) patients and 'flare' patients can be included. Exclusion Criteria: Renal disease unrelated to SLE (e.g. diabetes mellitus, other glomerular or tubulointerstitial disease, renovascular disease), or transplanted kidney. Estimated glomerular filtration rate (eGFR by MDRD) ≤20 mL/min per 1.73 m2 or serum creatinine >300 micromol/L (3.39 mg/dL) at screening. Renal biopsy showing cellular or fibrocellular crescent in more than 25% of glomeruli. CNS or other severe organ manifestation of lupus that necessitate aggressive immunosuppressive therapy on its own. Co-morbidities that require corticosteroid therapy (e.g. asthma, inflammatory bowel disease). Treatment with prednisolone (or prednisone, or equivalent) at >20 mg/D for over 4 weeks within the past 3 months. Treatment with MMF at >1.5 g/D for over 4 weeks within the past 3 months. Known hypersensitivity or intolerability to prednisolone (or prednisone, or equivalent), TAC, or MMF at a dose of 1.25 g or below per day. Subjects who are already on treatment with TAC, cyclosporine or any other calcineurin inhibitor for over 4 weeks within the past 12 months. Treatment with cyclophosphamide, leflunomide, or methotrexate for over 2 weeks, or use of biological agent(s) regardless of duration, within the past 6 months (Note: prior use of azathioprine, mizoribine, intravenous immunoglobulins and anti-malarials is allowed). Uncontrolled hypertension with systolic BP >160 mmHg or diastolic BP >95 mmHg. Women who are pregnant or breastfeeding. Women with childbearing potential or their male partners, who refuse to use an effective birth control method

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tak-Mao Daniel Chan

Phone

2255 4542

dtmchan@hku.hk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tak-Mao Daniel Chan

Organizational Affiliation

The University of Hong Kong

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Hong Kong

City

Hong Kong

Country

Hong Kong

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tak-Mao Daniel Chan

Phone

(852) 2255 4542

dtmchan@hku.hk

12. IPD Sharing Statement

Plan to Share IPD

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Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

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