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Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)

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ClinicalTrials.gov Identifier: NCT03549663
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary:
The trial is a random, open, control and monocentric trial. Mainly to assess the urine protein remission rate of tacrolimus (TAC) monotherapy for idiopathic membranous nephropathy (IMN). Assuming that the urine protein remission rate of 48-week TAC for monotherapy of IMN is not lower than that in treatment group of TAC combined with glucocorticoid, attempt on de-hormonal therapy in the future IMN therapy can be attempted on the basis of the trial results.

Condition or disease Intervention/treatment Phase
Idiopathic Membranous Nephropathy Drug: Tacrolimus Drug: Prednisone Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Random, Open, Control and Monocentric Clinical Research on Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)
Actual Study Start Date : July 4, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2021


Arm Intervention/treatment
Experimental: Tacrolimus monotherapy Drug: Tacrolimus
Tacrolimus capsules: 0.5mg/pill, 50 pills/box, AstellasPharma (China) Co., Ltd.; Tacrolimus capsules: 1mg/pill, 50 pills/box, Hangzhou ZhongmeiHuadong Pharmacy Co., Ltd. Start to administer on the randomized grouping day (D0) with an initial dose by weight: initial dose of 0.05-0.075mg/kg/d (bid) following a strict administration interval of 12 hours or fasting or 2 hours after meal. Adjust TAC dose according to 24-hour urine protein, plasma concentration and eGFR changes. It is recommended that plasma trough concentration should be remained at 5-8ng/ml and TAC dose during the whole therapy stage should not be lower than 0.5mg/d. Drugs should be stopped if the 6-month therapy is ineffective. After 6-month therapy, for those whose urine protein achieved complete remission (CR) or partial remission (PR), TAC dose should be reduced gradually with a total therapy duration of 48 weeks.

Active Comparator: Tacrolimus combined with hormone therapy Drug: Tacrolimus
Tacrolimus capsules: 0.5mg/pill, 50 pills/box, AstellasPharma (China) Co., Ltd.; Tacrolimus capsules: 1mg/pill, 50 pills/box, Hangzhou ZhongmeiHuadong Pharmacy Co., Ltd. Start to administer on the randomized grouping day (D0) with an initial dose by weight: initial dose of 0.05-0.075mg/kg/d (bid) following a strict administration interval of 12 hours or fasting or 2 hours after meal. Adjust TAC dose according to 24-hour urine protein, plasma concentration and eGFR changes. It is recommended that plasma trough concentration should be remained at 5-8ng/ml and TAC dose during the whole therapy stage should not be lower than 0.5mg/d. Drugs should be stopped if the 6-month therapy is ineffective. After 6-month therapy, for those whose urine protein achieved complete remission (CR) or partial remission (PR), TAC dose should be reduced gradually with a total therapy duration of 48 weeks.

Drug: Prednisone
Glucocorticoid (prednisone): 5mg/pill, 100 pills/bottle: Shanghai Sine Pharmaceutical Factory Co., Ltd. The initial dose of prednisone should be 0.5mg/kg/d orally (maximum dose of 40mg/d) and administration should be continued for 8-12 weeks; then reduced by the monthly decreased amount of 0.1mg/kg/d till to 0.2mg/kg/d (5-10mg) to maintain. Prednisone should be stopped after administration for the entire 48 weeks.
Other Name: Glucocorticoid




Primary Outcome Measures :
  1. Complete remission rate of 24-hour urine protein [ Time Frame: At week 48 ]
    The proportion of patients with complete remission of 24-hour urine protein in the total evaluated patients. Evaluation criteria of complete remission: post-therapy urine protein level is <0.3g/24h.


Secondary Outcome Measures :
  1. Partial remission remission rate of 24-hour urine protein [ Time Frame: At week 48 ]
    The proportion of patients with partial remission of 24-hour urine protein in the total evaluated patients. Evaluation criteria of partial remission: post-therapy urine protein decline is >50% compared with the peak value.

  2. PLA2R antibody negative conversion rate [ Time Frame: At week 48 ]
    The proportion of patients with PLA2R antibody negative conversion in the total evaluated patients. Evaluation criteria of negative conversion: PLA2R antibody level is <20RU/ml.

  3. Number of patients with adverse events [ Time Frame: up to 48 weeks ]
    Number of patients with adverse events



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 18 - 80 years;
  2. Those whose clinical manifestation and renal biopsy pathologic diagnosis are IMN (Stages I-IV) with secondary membranous nephropathy excluded;
  3. Those who meet any of the following high-risk IMN standards:

    • Urinary protein>8g/24h
    • Serum albumin<25g/l
    • Serum PLA2R levels are 5 times higher than normal
    • eGFR decline rate after confirmed IMN within 6-12 months is ≥30%
    • Patients with serious complications: pulmonary embolism, lower extremity static Vein thrombosis/embolism, acute renal injury, etc.
  4. Those without reaching the above high-risk IMN standard, but their course of disease is >6 months without spontaneous remission,and still present nephrotic syndrome;
  5. Patients who have signed the informed consent forms.

Exclusion Criteria:

  1. Those whose kidney pathological manifestation of interstitial fibrosis is >30%;
  2. Those who are positive in active Hepatitis B (including HBsAg, HBeAg and HBcAb or HBsAg, HBeAb and HBC) or serological indexes (HBsAg or/and HBeAg or/and HBcAb) or infected with Hepatitis C, tuberculosis, cytomegalovirus, severe fungal or HIV infection;
  3. Those who suffer from untreated active digestive tract ulcer within 3 months before random grouping;
  4. Those who suffer from uncured malignant tumor for less than 5 years
  5. Those who received glucocorticoid (prednisone or prednisolone), mycophenolatemofetil, tacrolimus, cyclosporine A and other drugs for treatment within 3 months before screen with a course of treatment exceeding 4 weeks or those who received cyclophosphamide (accumulated dose>1.0g);
  6. Those whose ALT, AST or total bilirubin content goes beyond 1.5 times above normal upper limit;
  7. Those who suffer from combined critical complications such as serious infection or other severe organ disease or dysfunction;
  8. Pregnant or lactating women;
  9. Those who are known to be allergic to drugs under trial or relevant products;
  10. Those who participated in other clinical trials within 3 months before inclusion;
  11. The patients who cannot comply with the research proposal as determined by the supervising physician.

Exit criteria

  1. Those with incomplete or partial relieved proteinuria for 6 months after treatment;
  2. Patients or their legal guardians voluntarily requests to withdraw;
  3. Those against the inclusion criteria and exclusion criteria;
  4. Those who need to take medications prohibited by the trail;
  5. Those with poor compliance or stopping the drug for over 2 weeks;
  6. Those with uncontrollable infection;
  7. Those whit elevated blood glucose during the treatment, which is still difficult to control after routine treatment by endocrinologists;
  8. In the TAC group, the eGFR decreased by >30%, the TAC dose was halved. And the drug concentration and renal function were reviewed after 2 weeks. If the eGFR decreased by <30%, it will continue to be used; if the eGFR still decreased by >30%, the TAC dose continues to halve, or give a minimum dose of 0.5mg / d. And the drug concentration and renal function were reviewed after 2 weeks. If the eGFR decreased by <30%, TAC will continue to be used, otherwise stop the drug;
  9. Those whose ALT, AST or bilirubin rises to more than 2 times the upper limit of normal value after treatment, and continues to increase for 2 weeks; those whose ALT, AST or bilirubin rises to more than 2 times the upper limit of normal value after 2 weeks of treatment with liver protection, the drug will be discontinued. If it cannot be recovered after 2 weeks, the patient will withdraw;
  10. Those with other unexplained severe comorbidities;
  11. Those with pregnancy during treatment;
  12. For security reasons, the research sponsor proposed to stop the study;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549663


Contacts
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Contact: Fujun Lin, MD,PhD +86-13917983703 linfujun@xinhuamed.com.cn

Locations
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China, Shanghai
Shanghai Xinhua Hospital affliated to Shanghai Jiao Tong University, School of Medicine Recruiting
Shanghai, Shanghai, China, 200092
Contact: Fujun Lin, MD,PhD         
Sponsors and Collaborators
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Investigators
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Principal Investigator: Fujun Lin, MD,PhD Shanghai Xinhua Hospital affiliated to Shanghai Jiao Tong University, School of Medicine

Publications:
KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int 2012, 2: 139-274.

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Responsible Party: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT03549663     History of Changes
Other Study ID Numbers: XH-18-006
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Kidney Diseases
Glomerulonephritis, Membranous
Urologic Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Prednisone
Glucocorticoids
Tacrolimus
Anti-Inflammatory Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action