A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis
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
1 other identifier
interventional
314
1 country
35
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2015
Typical duration for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 10, 2015
CompletedFirst Submitted
Initial submission to the registry
May 22, 2015
CompletedFirst Posted
Study publicly available on registry
May 29, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 10, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 10, 2018
CompletedNovember 1, 2024
October 1, 2024
3.5 years
May 22, 2015
October 30, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Remission rate (complete remission + partial remission)
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 Outcomes (18)
24-hour urine protein
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Change of 24-hour urine protein from baseline
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Serum albumin
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Change of Serum albumin from baseline
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Serum creatinine
at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
- +13 more secondary outcomes
Study Arms (2)
Tacrolimus group
EXPERIMENTALTacrolimus capsules + steroid
Cyclophosphamide group
ACTIVE COMPARATORCyclophosphamide injections + steroid
Interventions
Eligibility Criteria
You may qualify if:
- ≤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;
- hour urine protein ≥ 1.5g, Scr\<260umol/L (or 3mg/dL)
You may not qualify if:
- 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;
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Site CN00043
Hefei, Anhui, China
Site CN00030
Beijing, Beijing Municipality, China
Site CN00034
Beijing, Beijing Municipality, China
Site CN00041
Xiamen, Fujian, China
Site CN00056
Guangzhou, Guangdong, China
Site CN00017
Shenzhen, Guangdong, China
Site CN00045
Liuchow, Guangxi, China
Site CN00037
Nanning, Guangxi, China
Site CN00038
Nanning, Guangxi, China
Site CN00020
Shijiazhuang, Hebei, China
Site CN00047
Shijiazhuang, Hebei, China
Site CN00028
Zhengzhou, Henan, China
Site CN00023
Wuhan, Hubei, China
Site CN00024
Wuhan, Hubei, China
Site CN00027
Changsha, Hunan, China
Site CN00050
Changsha, Hunan, China
Site CN00012
Nanjing, Jiangsu, China
Site CN00013
Nanjing, Jiangsu, China
Site CN00025
Nanjing, Jiangsu, China
Site CN00049
Wuxi, Jiangsu, China
Site CN00026
Changchun, Jilin, China
Site CN00042
Changchun, Jilin, China
Site CN00005
Dalian, Liaoning, China
Site CN00018
Shenyang, Liaoning, China
Site CN00019
Shenyang, Liaoning, China
Site CN00032
Qingdao, Shandong, China
Site CN00001
Shanghai, Shanghai Municipality, China
Site CN00014
Shanghai, Shanghai Municipality, China
Site CN00015
Shanghai, Shanghai Municipality, China
Site CN00052
Taiyuan, Shanxi, China
Site CN00002
Chengdu, Sichuan, China
Site CN00003
Chengdu, Sichuan, China
Site CN00021
Tianjin, Tianjin Municipality, China
Site CN00044
Ürümqi, Xinjiang, China
Site CN00010
Hangzhou, Zhejiang, China
Related Publications (1)
Zheng Z, Zhang H, Peng X, Zhang C, Xing C, Xu G, Fu P, Ni Z, Chen J, Xu Z, Zhao MH, Li S, Huang X, Miao L, Chen X, Liu B, He Y, Li J, Liu L, Kadeerbai H, Liu Z, Liu Z. Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e224492. doi: 10.1001/jamanetworkopen.2022.4492.
PMID: 35353167DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma China, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2015
First Posted
May 29, 2015
Study Start
March 10, 2015
Primary Completion
September 10, 2018
Study Completion
September 10, 2018
Last Updated
November 1, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.