A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis

Lupus Nephritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02457221
• Other study ID #: F506-CL-0912
• Status: Completed
• Phase: Phase 3
• Start date: March 10, 2015
• Est. completion date: September 10, 2018

Study information

• Verified date: June 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: September 10, 2018
• Est. primary completion date: September 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Tacrolimus capsules
oral
• Cyclophosphamide injections
intravenous injection
• Prednisone
oral

Locations

Country	Name	City	State
China	Site CN00030	Beijing	Beijing
China	Site CN00034	Beijing	Beijing
China	Site CN00026	Changchun	Jilin
China	Site CN00042	Changchun	Jilin
China	Site CN00027	Changsha	Hunan
China	Site CN00050	Changsha	Hunan
China	Site CN00002	Chengdu	Sichuan
China	Site CN00003	Chengdu	Sichuan
China	Site CN00005	Dalian	Liaoning
China	Site CN00056	Guangzhou	Guangdong
China	Site CN00010	Hangzhou	Zhejiang
China	Site CN00043	Hefei	Anhui
China	Site CN00045	Liuzhou	Guangxi
China	Site CN00012	Nanjing	Jiangsu
China	Site CN00013	Nanjing	Jiangsu
China	Site CN00025	Nanjing	Jiangsu
China	Site CN00037	Nanning	Guangxi
China	Site CN00038	Nanning	Guangxi
China	Site CN00032	Qingdao	Shandong
China	Site CN00001	Shanghai	Shanghai
China	Site CN00014	Shanghai	Shanghai
China	Site CN00015	Shanghai	Shanghai
China	Site CN00018	Shenyang	Liaoning
China	Site CN00019	Shenyang	Liaoning
China	Site CN00017	Shenzhen	Guangdong
China	Site CN00020	Shijiazhuang	Hebei
China	Site CN00047	Shijiazhuang	Hebei
China	Site CN00052	Taiyuan	Shanxi
China	Site CN00021	Tianjin	Tianjin
China	Site CN00023	Wuhan	Hubei
China	Site CN00024	Wuhan	Hubei
China	Site CN00044	Wulumuqi	Xinjiang
China	Site CN00049	Wuxi	Jiangsu
China	Site CN00041	Xiamen	Fujian
China	Site CN00028	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma China, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24-hour urine protein		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Change of 24-hour urine protein from baseline		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Serum albumin		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Change of Serum albumin from baseline		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Serum creatinine		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Change of Serum creatinine from baseline		at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	eGFR comparing with baseline	eGFR: Estimated Glomerular Filtration Rate	at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24
Secondary	Percentage of patients converted to other immunosuppressive therapy		during 24 weeks
Secondary	Percentage of patients with serum creatinine rising to two times of the baseline		during 24 weeks
Secondary	Percentage of patients with dsDNA and ANA converting from positive to negative	ANA: Antinuclear Antibody	during 24 weeks
Secondary	SLE-DAI	SLE-DAI: Systemic Lupus Erythematosus - Disease Activity Index	at Week 4, 12 and 24
Secondary	Immune parameters assessed by ESR, C3, C4 and dsDNA	ESR: Erythrocyte Sedimentation Rate, C3, C4: Complement C3, C4, dsDNA: Anti-Double-Stranded DNA Antibodies	at Week 4, 12 and 24
Secondary	Change of SLE-DAI from baseline		at Week 4, 12 and 24
Secondary	Change of immune parameters from baseline		at Week 4, 12 and 24
Secondary	Renal biopsy AI (Active Index)		at Week 24
Secondary	CI (Chronic Index)		at Week 24
Secondary	Change of Renal biopsy AI (Active Index) from baseline		at Week 24
Secondary	Change of CI (Chronic Index) from baseline		at Week 24

External Links

•   Link to results on the Astellas Clinical Study Results website.