Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

NCT02630628 | Completed Phase 3

• 1 other identifier: ALNN-IIS-17JUL15-1
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Lupus Nephritis

Keywords

Lupus Nephritis; mycophenolate mofetil; tacrolimus

Outcome Measures

Primary Outcomes (1)

• 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: 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 Outcomes (24)

• Rate of complete renal remission

  96 weeks

• Rate of partial renal remission

  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)]

  48 weeks

• Refractory disease

  96 weeks

• Rate of non-renal flare

  96 weeks

Study Arms (2)

Tacrolimus

EXPERIMENTAL

route: oral duration: 96 weeks

Drug: Tacrolimus

Mycophenolate Mofetil

ACTIVE COMPARATOR

route: oral duration: 96 weeks

Drug: Mycophenolate mofetil

Interventions

Tacrolimus DRUG

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

Also known as: Prograf

Tacrolimus

Mycophenolate mofetil DRUG

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

Also known as: Cellcept

Mycophenolate Mofetil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Males or females aged 18 to 75 years inclusive at the time of screening.

You may not qualify if:

• 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 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.
• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Tak-Mao Daniel Chan

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 5, 2015
• First Posted: December 15, 2015
• Study Start: December 5, 2015
• Primary Completion: December 27, 2024
• Study Completion: December 27, 2024
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)