Inflammation REduction to Prevent cArdiovascular Injury in Renal Disease (REPAIR)

Phase 1 basket trial including 2 open-label single-arm cohorts: REPAIR CKD cohort and REPAIR Dialysis cohort. Open label colchicine 0.3 mg daily for 8 weeks followed, in patients who tolerated the 0.3 mg dose, by forced titration to 0.6 mg daily for 8 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Kidney Diseases; Renal Failure
• Intervention / Treatment: Drug: Colchicine

Detailed Description

The REPAIR CKD cohort will enroll 100 patients with chronic kidney disease not requiring dialysis. The REPAIR Dialysis cohort will enroll 100 patients with chronic kidney disease requiring chronic maintenance dialysis. Each participant will be followed for up to 17 weeks, to determine among adults with severe chronic kidney disease not requiring dialysis and (separately) in those requiring dialysis, the proportion who, over 8 weeks of treatment, discontinue colchicine 1) 0.3 mg daily and 2) 0.6 mg daily.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jessica Tyrwhitt, BSc; Email: jessica.tyrwhitt@phri.ca
• Study Contact Backup: Name: Courtney Christou, BSc; Phone Number: 905-521-2100; Email: courtney.christou@phri.ca; repair@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences Corporation
      • Principal Investigator: David Collister, MD, PhD
      • Contact: Marc Jeshcke, PhD; Phone Number: 40694 905-521-2100; Email: jeschke@hhsc.ca
      • Principal Investigator: Pavel Roshanov, MD, PhD
      • Principal Investigator: Lonnie Pyne, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. One of either:

   1.2 Estimated GFR using CKD-EPI 2021 equation of ≤30 ml/min/1.73m2 on at least two occasions separated by at least 2 months and do not yet require dialysis and are not expected by their treating nephrologist to require dialysis in the next 6 months (REPAIR CKD cohort), or 1.3 receiving chronic maintenance dialysis 2 or more times per week for the previous 90 days (REPAIR Dialysis cohort);

2. Age ≥18 years
3. Provide informed consent to participate.

Exclusion Criteria:

1. Currently treated with and cannot withdraw colchicine due to medical necessity; or
2. Known allergy/sensitivity to colchicine; or
3. Prior self-reported intolerance to colchicine at a dose of 0.6 mg daily or lower; or
4. Currently pregnant or planning to become pregnant or breastfeed during the study; or
5. Of childbearing potential AND do not have a negative pregnancy test OR do not agree to use two forms of contraception for the duration of the study; or
6. Anticipated living donor renal transplant within the next 6 months; or
7. Using a strong inhibitor of p-glycoprotein or strong inhibitor of CYP3A4 in the last 14 days; or
8. B12 deficiency not managed with intramuscular supplementation; or
9. Uncontrolled chronic diarrhea; or
10. Cirrhosis, or chronic active hepatitis; or
11. Pre-existent neuromuscular disease or persistent serum CK level > 3 times the upper limit of normal as measured within the past 60 days and determined to be non-transient through repeat testing; or

12. Patient with any of the following within the past 60 days:

    • white blood cell count < 3.0 X 109/L; or
    • platelet count <110 X 109/L; or
    • ALT or AST > 3 times the upper limit of normal (ULN); or
    • total bilirubin > 2 times ULN and not due to Gilbert syndrome.
13. Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: REPAIR CKD cohort; Patients will receive open label colchicine 0.3 mg daily for 8 weeks followed, in patients who tolerated the 0.3 mg dose, by forced titration to 0.6 mg daily for 8 weeks.	Drug: Colchicine; 0.3mg and 0.6mg tablets
Active Comparator: REPAIR Dialysis cohort; Patients will receive open label colchicine 0.3 mg daily for 8 weeks followed, in patients who tolerated the 0.3 mg dose, by forced titration to 0.6 mg daily for 8 weeks.	Drug: Colchicine; 0.3mg and 0.6mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose tolerance	Proportion of participants who permanently discontinue colchicine at either the 0.3 mg daily dose or 0.6 mg daily dose (to estimate the proportion who would discontinue the study drug at the 0.6 mg daily dose without titration).	Up to 17 weeks
Early discontinuations	Proportion of participants who permanently discontinue colchicine at the 0.3 mg daily dose.	Up to 17 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reason for drug discontinuation	To determine the reasons for temporary and permanent discontinuations of colchicine at the 0.3 mg and 0.6 mg daily doses.	Up to 17 weeks
Drug adherence	To determine degree of adherence to colchicine at the 0.3 mg and 0.6 mg daily doses.	Up to 17 weeks
Major Side Effects	To determine the risk of major side effects of colchicine at the 0.3 mg and 0.6 mg daily doses.	Up to 17 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colchicine Concentration	To determine serum concentrations of colchicine achieved at the study doses.	Up to 17 weeks

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: St. Joseph's Health Care London; Hamilton Academic Health Sciences Organization
• Investigators: Principal Investigator: Michael Walsh, MD, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Tolerance; Colchicine Resistance; Hematologic markers
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Inflammation; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: REPAIR

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