Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

NCT ID: NCT02630628

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-05
• Study Completion Date: 2024-12-27

Brief Summary

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

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.

Conditions

Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tacrolimus

route: oral duration: 96 weeks

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

Dosage: start at 2mg twice a day, then titrated according to therapeutic drug level monitoring using 12-hour post-dose blood sampling

Mycophenolate Mofetil

route: oral duration: 96 weeks

Group Type: ACTIVE_COMPARATOR

Mycophenolate mofetil

Intervention Type: DRUG

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

Interventions

Tacrolimus

Dosage: start at 2mg twice a day, then titrated according to therapeutic drug level monitoring using 12-hour post-dose blood sampling

Intervention Type: DRUG

Mycophenolate mofetil

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

Intervention Type: DRUG

Other Intervention Names

Prograf; Cellcept

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Professor Daniel Tak-Mao Chan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tak-Mao Daniel Chan

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

The University of Hong Kong

Hong Kong, , Hong Kong

Countries

Hong Kong

Other Identifiers

ALNN-IIS-17JUL15-1

Identifier Type: -

Identifier Source: org_study_id