Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)

April 1, 2019 updated by: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Random, Open, Control and Monocentric Clinical Research on Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

108

Phase

  • Not Applicable

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

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200092
        • Recruiting
        • Shanghai Xinhua Hospital affliated to Shanghai Jiao Tong University, School of Medicine
        • Contact:
          • Fujun Lin, MD,PhD

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 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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;

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Glucocorticoid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At week 48
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.
At week 48
Number of patients with adverse events
Time Frame: up to 48 weeks
Number of patients with adverse events
up to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

  • Principal Investigator: Fujun Lin, MD,PhD, Shanghai Xinhua Hospital affiliated to Shanghai Jiao Tong University, School of Medicine

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.

General Publications

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)

July 4, 2018

Primary Completion (Anticipated)

October 1, 2020

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

May 10, 2018

First Submitted That Met QC Criteria

June 7, 2018

First Posted (Actual)

June 8, 2018

Study Record Updates

Last Update Posted (Actual)

April 3, 2019

Last Update Submitted That Met QC Criteria

April 1, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XH-18-006

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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