Efficacy and Safety of Sirolimus Plus CNI Compared With MMF Plus CNI in ABO-i Kidney Transplant Recipients.

Evaluate the Efficacy and Safety of RaparoBell® Tablet Plus Calcineurin Inhibitors Compared With Mycophenolate Mofetil Plus Calcineurin Inhibitors in ABO Incompatible De Novo Living Kidney Transplant Recipients. [ART Study]

The purpose of this study is to evaluate the efficacy and safety of RaparoBell® Tablet Plus Calcineurin Inhibitors Compared with Mycophenolate Mofetil Plus Calcineurin Inhibitors in ABO incompatible De Novo Living Kidney Transplant Recipients.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Sirolimus Tab.; Drug: Mycophenolate Mofetil Cap./Tab.

Detailed Description

This study is Multi-center, Open-label, Randomized Controlled Phase 4 Study to Evaluate the Efficacy and Safety of RaparoBell® Tablet Plus Calcineurin Inhibitors Compared with Mycophenolate Mofetil Plus Calcineurin Inhibitors in ABO incompatible De Novo Living Kidney Transplant Recipients.

• Study Type: Interventional
• Enrollment (Anticipated): 158
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kyu Ha Huh, M.D, Ph.D; Phone Number: +82-2-2228-2138; Email: KHHUH@yuhs.ac
• Study Contact Backup: Name: Jung A Lee; Phone Number: +82-2-2194-0403; Email: junaa82@ckdpharm.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

[Time of Screening]

1. Patients who plan to be transplanted ABO incompatible living donor kidney or not past 35 days after kidney transplantation
2. More than the age of 19 years old
3. Agreement with written informed consent

[Time of Randomization]

1. Patients who have transplanted Kidney within 4 weeks(25 days to 35 days)
2. Patients who take CNI plus MMF after kidney transplantation

Exclusion Criteria:

[Time of Screening]

1. Patients who have transplanted non-kidney organs or have plan to be transplanted non-kidney organs
2. PRA > 50% before desenitization or positive results of DSA
3. Receive a kidney from a related donor who showed HLA identical
4. Positive in serology test(HIV, HBsAg, HCV) in recipients and/or donor
5. Allergic/hypersensitivity reaction in the history of Investigational drugs or additives
6. Women who are pregnant or breast feeding or not agree to the proper use of contraception during the trial
7. Patient has conversation impairment because of mental illness within 6months
8. Participated in other trial within 4 weeks
9. In investigator's judgement

[Time of Randomization]

1. Patients with acute rejection who have been clinically treated after kidney transplantation

2. At the time of Randomization

   • Treatment with active liver disease or Liver function test(T-bilirubin, AST, ALT)is over 3 times than upper normal limit
   • WBC< 2,500/mm^3, or platelet < 75,000/mm^3, or ANC < 1,300/mm^3
3. Patients who had plasmapheresis within 1 week
4. Patents who had a record of taking mTOR inhibitor before
5. In investigator's judgement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RaparoBell® Tablet; ABO-i De novo Living Kidney transplant recipients will be randomized after Kidney transplant.	Drug: Sirolimus Tab.; Orally, once-daily in the morning - The first dose is administered within maximum 6mg/day according to the investigator's judgement, check the blood concentration of Sirolimus at each visit and adjust the dose to acheive the blood concentration maintaining at 3~8ng/ml.; Other Names: RaparoBell® Tab.
Active Comparator: Mycophenolate Mofetil Tablet/Capsule; ABO-i De novo Living Kidney transplant recipients will be randomized after Kidney transplant.	Drug: Mycophenolate Mofetil Cap./Tab.; Up to 1g BID(total 2g daily), PO; Other Names: Myrept® Cap./Tab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite efficacy failure	Composite efficacy failure include biopsy-confired acute rejection, graft loss, death, or follow-up failure	Until 48 weeks after taking medicine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite efficacy failure	Composite efficacy failure include biopsy-confired acute rejection, graft loss, death, or follow-up failure	Until 24 weeks after taking medicine
Incidence of biopsy-confirmed acute rejection	Banff Criteria	Until 24weeks and 48weeks after taking medicine
The pathological results and time of occurrence and method of treatment, result of the treatment of acute rejection confirmed by biopsy	Banff Criteria	Until 24weeks and 48weeks after taking medicine
Survival rate	transplanted organ and patients	Until 24weeks and 48weeks after taking medicine
Function of Kidney	eGFR using MDRD(Modification of Diet in Renal Disease) method	Until 24weeks and 48weeks after taking medicine
Incidence of CMV, BKV infection	Incidence of CMV, BKV infection	Until 24weeks and 48weeks after taking medicine

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Chair: Kyu Ha Huh, M.D, Ph.D, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Sirolimus; ABO incompatible
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Sirolimus
• Other Study ID Numbers: B110_01KT2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No