Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy

• ClinicalTrials.gov Identifier: NCT03864250
• Recruitment Status: Unknown
• First Posted: March 6, 2019
• Last Update Posted: June 25, 2019
• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Information provided by (Responsible Party): Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Tracking Information

• First Submitted Date: March 4, 2019
• First Posted Date: March 6, 2019
• Last Update Posted Date: June 25, 2019
• Actual Study Start Date: November 26, 2018
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2019)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 4, 2019)

• 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.
• 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.
• Number of patients with adverse events [ Time Frame: Up to 48 weeks ]
  Number of patients with adverse events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy
• Official Title: Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy: A Randomized, Open, Controlled, Multicenter Clinical Trial
• Brief Summary: This random, open, control and multicenter clinical trial mainly aims to assess the urine protein remission rate of tacrolimus (TAC) monotherapy for idiopathic membranous nephropathy (IMN).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Tacrolimus
• Idiopathic Membranous Nephropathy
• Clinical Trial

Intervention

• Drug: Tacrolimus
  The initial dose of TAC is 0.05-0.1 mg/kg/d, taking 2 hours before and after meals. The interval is strictly 12 hours. The blood concentration is measured after taking the drug. According to the concentration of blood drug valley, the dose of tacrolimus (blood concentration of ≤10ng/ml) is adjusted. If the blood drug concentration is low, the drug dose (≤0.1mg/kg/d) is increased accordingly. After 6 months of treatment, the drug is discontinued. The TAC dose is maintained at the original dose after 6 months of treatment with complete or partial remission of urinary protein until the end of the 48-week trial.
• Drug: Prednisone
  The initial dose of prednisone is 0.5 mg/kg/d orally (maximum dose 40 mg/d), and after 8-12 weeks, the dose was gradually reduced until discontinuation. TAC treatment is given at the same time (the treatment plan is the same as the experimental group).

Study Arms

• Experimental: Tacrolimus monotherapy
  Intervention: Drug: Tacrolimus
• Active Comparator: Tacrolimus combined with hormone therapy
  Interventions:

  • Drug: Tacrolimus
  • Drug: Prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 4, 2019): 124
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Eligibility 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 infection, syphilis 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 less than 5 years;
5. Those who received glucocorticoids (prednisone or prednisolone), mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, tripterygium and other immunosuppressive agents for treatment within 3 months before screening;
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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03864250
• Other Study ID Numbers: XH-19-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Verification Date: March 2019