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TOP-CKD: Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease

Sponsor
Veterans Medical Research Foundation (Other)
Overall Status
Recruiting
CT.gov ID
NCT04258397
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), San Diego Veterans Healthcare System (U.S. Fed), University of California, San Diego (Other), University of California, San Francisco (Other), Genentech, Inc. (Industry)
200
Enrollment
2
Locations
2
Arms
49.2
Anticipated Duration (Months)
100
Patients Per Site
2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Kidney disease is a global health problem, affecting more than 10% of the world's population and more than half of adults over 70 years of age in the United States. Persons with kidney disease are at higher risk for cardiovascular disease, heart failure, physical function decline, and mortality. Kidney scarring is a dominant factor in the development of kidney disease. Our group has evaluated several tests to determine the severity of scarring without requiring kidney biopsies, using MRI imaging scans and evaluating markers of scarring that we can measure in the urine. In this study we will use these measures to evaluate pirfenidone as a promising potential new treatment for patients with kidney disease.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The TOP-CKD clinical trial is a randomized, double-blind, placebo-controlled interventional study, phase 2 trial of pirfenidone vs. placebo in 200 persons with Chronic Kidney Disease (CKD) with an eGFR ≥ 20 ml/min/1.73 m2 and a risk of progression to End Stage Renal Disease (ESRD) of at least 1% over five years. Participants receive treatment for 12 months, followed by a 6 month off-treatment follow-up period. Kidney scarring, also known as fibrosis, is a dominant factor in the development of kidney disease. This study will evaluate several tests to determine the severity of scarring without requiring kidney biopsies, using MRI imaging scans and evaluating markers of scarring that we can measure in the urine. We will use these measures to evaluate pirfenidone as a promising potential new treatment for patients with CKD.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Other
Official Title:
Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease (TOP-CKD)
Actual Study Start Date :
Oct 26, 2020
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
Dec 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Experimental, pirfenidone

Pirfenidone 267 mg capsules Randomized participants will take 5 capsules (1335 mg pirfenidone): 2 pills in the morning, 1 mid-day, and 2 in the evening, with meals.

Drug: Pirfenidone
Pirfenidone vs. matching placebo
Other Names:
  • ESBRIET

    		•
    Placebo Comparator: Placebo, pirfenidone

    Pirfenidone placebo capsules Randomized participants will take 5 capsules (1335 mg pirfenidone): 2 pills in the morning, 1 mid-day, and 2 in the evening, with meals.

    Drug: matching placebo
    matching placebo
    Other Names:
  • ESBRIET

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in kidney fibrosis, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI). [Baseline to Month 12]

      The slope of change in apparent diffusion coefficient of the cortex of the kidney on the diffusion-weighted renal MRI over 12 months.

    2. Change from baseline in kidney fibrosis, as assessed by urinary markers of tubulo-interstitial fibrosis. [Baseline to Month 12]

      The slope of change of urine alpha 1 microglobulin (α1M), N-terminal procollagen type 3 peptide (PIIINP), and monocyte chemoattractant protein-1 (MCP-1) over 12 months.

    Secondary Outcome Measures

    1. Change from baseline in kidney function, as assessed by eGFR. [Baseline to Month 18]

      Change in eGFR will be evaluated as a secondary endpoint, using linear mixed models with random intercepts and slopes. Estimates from the linear mixed models will be interpretable as annual change in slope.

    2. Change from baseline in kidney function, as assessed by urine albumin to creatinine ratio (ACR). [Baseline to Month 18]

      Change in ACR will be evaluated as a secondary endpoint, using linear mixed models with random intercepts and slopes. Estimates from the linear mixed models will be interpretable as annual change in slope. Because urine concentrations of ACR are typically right-skewed, we will use a log transformation to normalize its distribution.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with eGFR ≥20 ml/min/1.73m2 using the CKD-EPI Creatinine equation.

    • Four variable Kidney Failure Risk Equation (KFRE) 5 year risk score >1%

    • Age 21 years or older.

    Exclusion Criteria:

    To be determined at the screening visit or, for laboratory data, within 3 months of the screening visit if available from clinical care.

    • Participants with known autosomal dominant polycystic kidney disease.

    • Use or planned use of drugs that inhibit CYP1A2 which may increase pirfenidone exposure ( for example, artemisin, atazanavir, cimetidine, ciprofloxacin, enoxacin, ethinyl estradiol, fluvoxamine, mexiletine, tacrine, thiabendazole, or zileuton).

    • Liver disease: clinical cirrhosis by imaging or physician diagnosis; alcohol use > 14 drinks/week; or aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin concentrations > 2 times the upper limit of normal (ULN) based on thresholds set at each site's local clinical laboratory.

    • Clinical idiopathic pulmonary fibrosis (IPF) by imaging or physician diagnosis (pirfenidone is indicated for patients with IPF).

    • Electrocardiogram (ECG) with a QTc interval > 500 msec at screening (pirfenidone can prolong QTc).

    • Family or personal history of long QT Syndrome.

    • Known hypersensitivity to pirfenidone.

    • Current use of tobacco, including cigarettes, cigars, chewing tobacco, or vaping products. (Current use is defined as any use in the past 3 months).

    • Physical inability, claustrophobia or other contra-indication to obtaining MRI measurements.

    • Current participation in another clinical trial (observational studies are exempted).

    • Systemic immunosuppressive medications (<10 mg daily prednisone or inhaled steroids are exempted).

    • Malignancy within 2 years (non-melanoma skin and localized prostate carcinoma are exempted).

    • Institutionalized individuals (e.g. prisoners, long term care residents).

    • Pregnancy, planning to become pregnant, or currently breast-feeding; women under 55 will need to either have a reliable method of birth control (IUD {intrauterine device}, oral contraceptive pills ) or have no menses in the preceding 2 years.

    • Life expectancy < 12 months as assessed by the site investigator.

    • Plans to leave the immediate area in < 12 months.

    • Anticipated need for dialysis or kidney transplantation within 12 months.

    • Hospitalization within the past 30 days (24-hour observation admissions are exempted).

    • Active alcohol or substance abuse within the last 12 months, as assessed by the site investigator.

    • Active treatment of uncontrolled psychiatric disease, as assessed by the site investigator.

    • Perceived inability to adhere to the medical regimen or comply with recommendations, as determined by the site investigator.

    • Inability or unwillingness to travel to study visits.

    • Any condition that, in the opinion of the site investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 VA San Diego Healthcare System San Diego California United States 92161
    2 University of California, San Francisco San Francisco California United States 94143

    Sponsors and Collaborators

    • Veterans Medical Research Foundation
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    • San Diego Veterans Healthcare System
    • University of California, San Diego
    • University of California, San Francisco
    • Genentech, Inc.

    Investigators

    • Principal Investigator: Joachim H Ix, MD,MAS, Veterans Medical Research Foundation at VASDHS

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Joachim H. Ix, Professor of Medicine; Chief, Division of Nephrology-Hypertension, UCSD; Attending Physician VASDHS, Veterans Medical Research Foundation
    ClinicalTrials.gov Identifier:
    NCT04258397
    Other Study ID Numbers:
    • H200014
    • U01DK111510
    First Posted:
    Feb 6, 2020
    Last Update Posted:
    Apr 27, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Joachim H. Ix, Professor of Medicine; Chief, Division of Nephrology-Hypertension, UCSD; Attending Physician VASDHS, Veterans Medical Research Foundation
    Fibrosis
    Scarring
    CKD
    Additional relevant MeSH terms:
    Kidney Diseases
    Renal Insufficiency, Chronic
    Pirfenidone

    Study Results

    No Results Posted as of Apr 27, 2022