- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02457221
A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis
May 19, 2022 updated by: Astellas Pharma China, Inc.
A Phase III, Randomized, Open, Parallel-controlled, Multi-center Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis
The objective of this study is to evaluate the efficacy and safety of Tacrolimus capsules for induction remission in patients with lupus nephritis, and compare the efficacy and safety with Cyclophosphamide injections.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.
Study Type
Interventional
Enrollment (Actual)
314
Phase
- 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 Locations
-
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Anhui
-
Hefei, Anhui, China
- Site CN00043
-
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Beijing
-
Beijing, Beijing, China
- Site CN00030
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Beijing, Beijing, China
- Site CN00034
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Fujian
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Xiamen, Fujian, China
- Site CN00041
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Guangdong
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Guangzhou, Guangdong, China
- Site CN00056
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Shenzhen, Guangdong, China
- Site CN00017
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Guangxi
-
Liuzhou, Guangxi, China
- Site CN00045
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Nanning, Guangxi, China
- Site CN00037
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Nanning, Guangxi, China
- Site CN00038
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Hebei
-
Shijiazhuang, Hebei, China
- Site CN00020
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Shijiazhuang, Hebei, China
- Site CN00047
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Henan
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Zhengzhou, Henan, China
- Site CN00028
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Hubei
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Wuhan, Hubei, China
- Site CN00023
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Wuhan, Hubei, China
- Site CN00024
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Hunan
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Changsha, Hunan, China
- Site CN00027
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Changsha, Hunan, China
- Site CN00050
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Jiangsu
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Nanjing, Jiangsu, China
- Site CN00012
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Nanjing, Jiangsu, China
- Site CN00013
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Nanjing, Jiangsu, China
- Site CN00025
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Wuxi, Jiangsu, China
- Site CN00049
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Jilin
-
Changchun, Jilin, China
- Site CN00026
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Changchun, Jilin, China
- Site CN00042
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Liaoning
-
Dalian, Liaoning, China
- Site CN00005
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Shenyang, Liaoning, China
- Site CN00018
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Shenyang, Liaoning, China
- Site CN00019
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Shandong
-
Qingdao, Shandong, China
- Site CN00032
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Shanghai
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Shanghai, Shanghai, China
- Site CN00001
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Shanghai, Shanghai, China
- Site CN00014
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Shanghai, Shanghai, China
- Site CN00015
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Shanxi
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Taiyuan, Shanxi, China
- Site CN00052
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Sichuan
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Chengdu, Sichuan, China
- Site CN00002
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Chengdu, Sichuan, China
- Site CN00003
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Tianjin
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Tianjin, Tianjin, China
- Site CN00021
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Xinjiang
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Wulumuqi, Xinjiang, China
- Site CN00044
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Zhejiang
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Hangzhou, Zhejiang, China
- Site CN00010
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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
Ages Eligible for Study
18 years to 60 years (ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 18.5≤Body Mass Index (BMI) <27;
- Diagnosed as systemic lupus erythematosus (based on American Rheumatism Association Diagnostic Criteria 1997)
- Diagnosed as III, IV, V, III + V, IV + V lupus nephritis (according to the LN classification in International Society of Nephrology and Renal Pathology Society (ISN/RPS) 2003) within 24 weeks before enrollment with renal biopsy;
- 24-hour urine protein ≥ 1.5g, Scr<260umol/L (or 3mg/dL)
Exclusion Criteria:
- Class II or VI lupus nephritis or renal biopsy chronic index (CI) > 3 or with TMA;
- Received immunosuppressants (mycophenolate mofetil (MMF), cyclosporine, methotrexate, mechlorethamine, chlorambucil, tripterygium preparations, leflunomide etc.) treatment with a duration of more than one week within 30 days prior to enrollment;
- Received tacrolimus (except for topical use) or cyclophosphamide treatment within 30 days prior to enrollment;
- Received a course of methylprednisolone (MP) pulse therapy or gamma globulin treatment or plasma exchange within 30 days prior to enrollment;
- Patients with history of allergies to tacrolimus, cyclophosphamide or methylprednisolone;
- Pregnancy, lactation or patient unwilling to take contraceptive measures;
- Patients with estimated maintenance dialysis for more than eight weeks; or dialysis for more than two weeks prior to entering observation;
- Patients received kidney transplantation or plan to have kidney transplantation recently;
- Serum creatinine (Scr) ≥260umol/L (or 3mg/dL) or creatinine clearance rate (Ccr) < 30ml/(min.1.73m2); according to Cockcroft-Gault formula: Ccr (ml/sec) = [(140- age)× Weight (kg)] × K / [72×Scr (umol/L) ×0.6786], Female K = 0.85, Male K = 1.0;
- Patients suffering from liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal lab value) or bilirubin more than 3 times the upper limit of normal lab value;
- Patients diagnosed with diabetes;
- History of gastrointestinal bleeding or pancreatitis within 3 months;
- Uncontrollable hyperkalemia after dietary therapy or reduction of potassium treatment (exceed the upper limit of normal lab value);
- Patients suffering from lupus pneumonia or lung injury;
- Patients with anemia (hemoglobin <7g/dl) or bone marrow suppression (WBC <3.0×109/L, and/or neutrophils <1.5×109/L, and/or platelets <50×109/L) not secondary to systemic lupus erythematosus;
- With congenital heart disease, arrhythmia, heart failure or other severe cardiovascular diseases;
- With refractory hypertension (defined as blood pressure still exceeds 180/110 mmHg despite taking three different types of antihypertensive drugs [one of them is diuretic] simultaneously);
- Patients with recurrent tumors within 5 years;
- Severe infection that requires intravenous antibiotics within 2 weeks prior to enrollment;
- Patients with infection of hepatitis B virus or hepatitis C virus; patients with active tuberculosis; patients with severe immunodeficiency diseases (including active cytomegalovirus infection (positive CMV IgM antibody), or human immunodeficiency virus (HIV) infection, etc.);
- Patients with lupus encephalopathy or other life-threatening complication of systemic lupus erythematosus;
- Patients participated in other clinical trials within three months before enrollment
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
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tacrolimus group
Tacrolimus capsules + steroid
|
oral
oral
Other Names:
|
Active Comparator: Cyclophosphamide group
Cyclophosphamide injections + steroid
|
oral
intravenous injection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Remission rate (complete remission + partial remission)
Time Frame: at 24 weeks
|
complete remission: urine protein < 0.5g/24hr, and serum albumin≥3.5g/dl,
and stable renal function (Scr increase ≤ 15% baseline value) partial remission: urine protein 0.5-3.5g/24hr
(≥ 0.5 g/24hr and < 3.5 g/24hr), and urine protein decreased by >50% comparing with the baseline, and serum albumin ≥ 3.0g/dl, and stable renal function (Scr increase ≤ 15% baseline value)
|
at 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24-hour urine protein
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
|
Change of 24-hour urine protein from baseline
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
|
Serum albumin
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
|
Change of Serum albumin from baseline
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
|
Serum creatinine
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
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at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
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Change of Serum creatinine from baseline
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
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eGFR comparing with baseline
Time Frame: at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
eGFR: Estimated Glomerular Filtration Rate
|
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
|
Percentage of patients converted to other immunosuppressive therapy
Time Frame: during 24 weeks
|
during 24 weeks
|
|
Percentage of patients with serum creatinine rising to two times of the baseline
Time Frame: during 24 weeks
|
during 24 weeks
|
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Percentage of patients with dsDNA and ANA converting from positive to negative
Time Frame: during 24 weeks
|
ANA: Antinuclear Antibody
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during 24 weeks
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SLE-DAI
Time Frame: at Week 4, 12 and 24
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SLE-DAI: Systemic Lupus Erythematosus - Disease Activity Index
|
at Week 4, 12 and 24
|
Immune parameters assessed by ESR, C3, C4 and dsDNA
Time Frame: at Week 4, 12 and 24
|
ESR: Erythrocyte Sedimentation Rate, C3, C4: Complement C3, C4, dsDNA: Anti-Double-Stranded DNA Antibodies
|
at Week 4, 12 and 24
|
Change of SLE-DAI from baseline
Time Frame: at Week 4, 12 and 24
|
at Week 4, 12 and 24
|
|
Change of immune parameters from baseline
Time Frame: at Week 4, 12 and 24
|
at Week 4, 12 and 24
|
|
Renal biopsy AI (Active Index)
Time Frame: at Week 24
|
at Week 24
|
|
CI (Chronic Index)
Time Frame: at Week 24
|
at Week 24
|
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Change of Renal biopsy AI (Active Index) from baseline
Time Frame: at Week 24
|
at Week 24
|
|
Change of CI (Chronic Index) from baseline
Time Frame: at Week 24
|
at Week 24
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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)
March 10, 2015
Primary Completion (Actual)
September 10, 2018
Study Completion (Actual)
September 10, 2018
Study Registration Dates
First Submitted
May 22, 2015
First Submitted That Met QC Criteria
May 27, 2015
First Posted (Estimate)
May 29, 2015
Study Record Updates
Last Update Posted (Actual)
May 25, 2022
Last Update Submitted That Met QC Criteria
May 19, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Kidney Diseases
- Urologic Diseases
- Connective Tissue Diseases
- Glomerulonephritis
- Lupus Erythematosus, Systemic
- Nephritis
- Lupus Nephritis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Calcineurin Inhibitors
- Cyclophosphamide
- Prednisone
- Tacrolimus
Other Study ID Numbers
- F506-CL-0912
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
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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