UMIN-CTR Clinical Trial

Basic information
Public 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
Acronym	Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis
Scientific 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
Scientific Title:Acronym	Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis
Region	Japan Asia(except Japan)

Condition
Condition	systemic lupus erythematosus
Classification by specialty	Clinical immunology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Prospective, randomized, parallel-group controlled, open-label, international (Asian) multicenter, comparison of corticosteroids combined with TAC and corticosteroids combined with MMF.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	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 ] [ Designated as safety issue: Yes ] 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 4. 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
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Cluster
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Tacrolimus
Interventions/Control_2	Mycophenolate Mofetil
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key 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.
Key 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 for over 4 weeks within the past 12 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
Target sample size	200

Research contact person
Name of lead principal investigator	1st name Middle name Last name Tak-Mao Daniel Chan
Organization	The University of Hong Kong
Division name	Department of Medicine
Zip code
Address	4/F, Professional Block, Queen Mary Hospital
TEL	+852-2255-4449
Email	dtmchan@hku.hk

Public contact
Name of contact person	1st name Middle name Last name Tak-Mao Daniel Chan
Organization	The University of Hong Kong
Division name	Department of Medicine
Zip code
Address	4/F, Professional Block, Queen Mary Hospital
TEL	+852-2255-4449
Homepage URL
Email	dtmchan@hku.hk

Sponsor
Institute	The University of Hong Kong
Institute
Department

Funding Source
Organization	The University of Hong Kong
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT02630628
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 12 Month 25 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2015 Year 07 Month 17 Day
Date of IRB	2015 Year 09 Month 02 Day
Anticipated trial start date	2015 Year 12 Month 05 Day
Last follow-up date	2021 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 12 Month 19 Day
Last modified on	2020 Year 06 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000029135