Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

September 21, 2025 updated by: Professor Daniel Tak-Mao Chan, The University of Hong Kong

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
130

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Tak-Mao Daniel Chan
  • Phone Number: 2255 4542
  • Email: dtmchan@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • The University of Hong Kong

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Biopsy-proven LN Class III/IV±V (ISN/RPS 2003), with biopsy performed within 12 weeks of randomization.
  2. Positive anti-dsDNA.
  3. Active LN with proteinuria (urine protein/creatinine ratio ≥1.0 or 24-hr urine protein ≥1.0 g at baseline), with or without hematuria.
  4. Both 'incident' (i.e. new) patients and 'flare' patients can be included.
  5. Males or females aged 18 to 75 years inclusive at the time of screening.

Exclusion Criteria:

  1. Renal disease unrelated to SLE (e.g. diabetes mellitus, other glomerular or tubulointerstitial disease, renovascular disease), or transplanted kidney.
  2. 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.
  3. Renal biopsy showing cellular or fibrocellular crescent in more than 25% of glomeruli.
  4. CNS or other severe organ manifestation of lupus that necessitate aggressive immunosuppressive therapy on its own.
  5. Co-morbidities that require corticosteroid therapy (e.g. asthma, inflammatory bowel disease).
  6. Treatment with prednisolone (or prednisone, or equivalent) at ≥20 mg/D for over 4 weeks within the past 3 months.
  7. Treatment with MMF at >1.5 g/D for over 4 weeks within the past 3 months.
  8. Known hypersensitivity or intolerability to prednisolone (or prednisone, or equivalent), TAC, or MMF at a dose of 1.25 g or below per day.
  9. Subjects who are already on treatment with TAC, cyclosporine or any other calcineurin inhibitor on the day of screening; or have received treatment with TAC, cyclosporine or other calcineurin inhibitor for over 4 weeks within the past 6 months.
  10. 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).
  11. Uncontrolled hypertension with systolic BP >160 mmHg or diastolic BP >95 mmHg.
  12. Women who are pregnant or breastfeeding.
  13. Women with childbearing potential or their male partners, who refuse to use an effective birth control method

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tacrolimus
route: oral duration: 96 weeks
Drug: Tacrolimus
Dosage: start at 2mg twice a day, then titrated according to therapeutic drug level monitoring using 12-hour post-dose blood sampling
Other Names:
  • Prograf
Active Comparator: Mycophenolate Mofetil
route: oral duration: 96 weeks
Drug: Mycophenolate mofetil
Dosage: start at 1g twice a day, then taper as per protocol
Other Names:
  • Cellcept

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)]
Time Frame: 96 weeks

Sustained RR defined as satisfying all of the following criteria:

  1. proteinuria improved by ≥50% compared with baseline
  2. 24-hr urine protein <1 g
  3. serum creatinine not higher than 15% above baseline level or eGFR not less than 60 mL/min/1.73m2
  4. no occurrence of disease flare AFTER achieving response to treatment. Disease flare is defined as the need for 'rescue' immunosuppressive therapy with any one of the following i. increase of prednisolone dose from ≤7.5 mg/D to ≥15 mg/D for 4 weeks or longer ii. change of originally assigned immunosuppressive agent iii. addition of immunosuppressive medications prohibited in protocol
96 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Refractory disease
Time Frame: 96 weeks
Never achieving partial renal remission since commencement of study
96 weeks
Changes in SELENA-SLEDAI scores
Time Frame: 96 weeks
Changes in SELENA-SLEDAI scores from baseline to week 96
96 weeks
Changes in PGA scores
Time Frame: 96 weeks
Changes in PGA scores from baseline to week 96
96 weeks
Changes in SFI scores
Time Frame: 96 weeks
Changes in SFI scores from baseline to week 96
96 weeks
Changes in BILAG (2004) scores
Time Frame: 96 weeks
Changes in BILAG (2004) scores from baseline to week 96
96 weeks
Rate of complete renal remission
Time Frame: 96 weeks
  • proteinuria not higher than 0.5 g/D
  • serum creatinine not higher than 15% above baseline level or eGFR not less than 60 mL/min/1.73m2
96 weeks
Rate of partial renal remission
Time Frame: 96 weeks
  • proteinuria above 0.5 g/D and below 3 g/D and with ≥50% improvement compared with baseline level
  • serum creatinine not higher than 15% above baseline level or eGFR not less than 60 mL/min/1.73m2
96 weeks
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)]
Time Frame: 48 weeks

Sustained RR defined as satisfying all of the following criteria:

  1. proteinuria improved by ≥50% compared with baseline
  2. 24-hr urine protein <1 g
  3. serum creatinine not higher than 15% above baseline level or eGFR not less than 60 mL/min/1.73m2
  4. no occurrence of disease flare AFTER achieving response to treatment. Disease flare is defined as the need for 'rescue' immunosuppressive therapy with any one of the following i. increase of prednisolone dose from ≤7.5 mg/D to ≥15 mg/D for 4 weeks or longer ii. change of originally assigned immunosuppressive agent iii. addition of immunosuppressive medications prohibited in protocol
48 weeks
Rate of non-renal flare
Time Frame: 96 weeks
Disease flare defined by the need for 'rescue' immunosuppressive therapy with any one of the following i. increase of prednisolone dose from ≤7.5 mg/D to ≥15 mg/D for 4 weeks or longer ii. change of originally assigned immunosuppressive agent iii. addition of immunosuppressive medications prohibited in protocol
96 weeks
Incidence of acute kidney injury
Time Frame: 96 weeks
Number of patients who had increase of serum creatinine level ≥15% from baseline and whether the increase was reversible or irreversible
96 weeks
Incidence of TAC blood level above target range
Time Frame: 96 weeks
Number of patients who had 12-hour post dose TAC blood level above i. 8 ng/mL (from baseline to end of week 24) ii. 7 ng/mL (from start of week 25 to end of week 48, and from start of week 49 to end of week 96 for patients who had serum creatinine level <150 micromol/L) iii. 6 ng/mL (from start of week 49 to end of week 96 for patients who had serum creatinine level ≥150 micromol/L)
96 weeks
Incidence of new onset hypertension or worsening hypertensive control
Time Frame: 96 weeks
Number of patients who had new onset hypertension (blood pressure >140/90 mmHg) or worsening hypertensive control that required increase of number or dose of anti-hypertensive medications
96 weeks
Rate of infection
Time Frame: 96 weeks
Number of patients who had infection that required hospitalization and its causative agents
96 weeks
Rate of Hospitalization
Time Frame: 96 weeks
Number of patients who had been hospitalized, the cause and duration of hospitalization
96 weeks
Incidence of hyperkalemia
Time Frame: 96 weeks
Number of patients who had serum potassium level >5.6 mmol/L
96 weeks
Incidence of metabolic acidosis
Time Frame: 96 weeks
Number of patients who had serum bicarbonate level <17 mmol/L
96 weeks
Incidence of new onset diabetes mellitus
Time Frame: 96 weeks
Number of patients who had fasting glucose > 6.0 mmol/L and/or required addition of blood glucose lowering drug(s)
96 weeks
Incidence of new onset hypercholesterolemia
Time Frame: 96 weeks
Number of patients who had total cholesterol> 5.0 mmol/L and low density lipoprotein >3.4 mmol/L presented at 6 months or beyond from baseline and/or required addition of lipid-lowering drug(s)
96 weeks
Rate of treatment intolerance leading to premature study discontinuation
Time Frame: 96 weeks
Definition of treatment intolerance i. severe gastrointestinal disturbance or marrow suppression (white blood cell count <2×10^9/L OR platelet count <50×10^9/L OR hemoglobin <8 g/dL) judged due to MMF and persisted despite reduction of MMF dosage to < 1.25 g per day ii. significant hand-tremor or neurotoxicity related to TAC
96 weeks
Rate of disease complication leading to premature study discontinuation
Time Frame: 96 weeks
Number of patients who developed complication that led to premature study discontinuation
96 weeks
Rate of disease flare leading to premature study discontinuation
Time Frame: 96 weeks
Disease flare is defined as the need for 'rescue' immunosuppressive therapy with any one of the following i. increase of prednisolone dose from ≤7.5 mg/D to ≥15 mg/D for 4 weeks or longer ii. change of originally assigned immunosuppressive agent iii. addition of immunosuppressive medications prohibited in protocol
96 weeks
Number of patients who failed to adhere to protocol defined corticosteroid reduction regimen
Time Frame: 96 weeks
Failure to adhere to corticosteroid reduction regimen was defined as deviation from protocol-defined corticosteroid dose by >5mg/D for >3 weeks due to unsatisfactory treatment response or new-onset disease activity.
96 weeks
Incidence of adverse events
Time Frame: 96 weeks
Number and type of adverse events, irrespective of whether the event was treatment-related or not
96 weeks
Incidence of serious adverse events
Time Frame: 96 weeks
Number and type of serious adverse events, irrespective of whether the event was treatment-related or not
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Hong Kong

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tak-Mao Daniel Chan, The University of Hong Kong

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 5, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 27, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 27, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 15, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALNN-IIS-17JUL15-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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