Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease

NCT04258397 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: H200014U01DK111510
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Kidney Disease

Keywords

Fibrosis; Scarring; CKD

Outcome Measures

Primary Outcomes (2)

• Change from baseline in kidney fibrosis, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI).

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

  Baseline to Month 12

• Change from baseline in kidney fibrosis, as assessed by urinary markers of tubulo-interstitial fibrosis.

  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.

  Baseline to Month 12

Secondary Outcomes (2)

• Change from baseline in kidney function, as assessed by eGFR.

  Baseline to Month 18

• Change from baseline in kidney function, as assessed by urine albumin to creatinine ratio (ACR).

  Baseline to Month 18

Study Arms (2)

Experimental, pirfenidone

ACTIVE COMPARATOR

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

Placebo, pirfenidone

PLACEBO COMPARATOR

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

Interventions

Pirfenidone DRUG

Pirfenidone vs. matching placebo

Also known as: ESBRIET

Experimental, pirfenidone

matching placebo DRUG

matching placebo

Also known as: ESBRIET

Placebo, pirfenidone

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 {OCPs}) or have no menses in the preceding 2 years.

Sponsors & Collaborators

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

Study Sites (2)

VA San Diego Healthcare System

San Diego, California, 92161, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (17)

• Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012 Jan 14;379(9811):165-80. doi: 10.1016/S0140-6736(11)60178-5. Epub 2011 Aug 15.

  PMID: 21840587 BACKGROUND

• Fried LF, Biggs ML, Shlipak MG, Seliger S, Kestenbaum B, Stehman-Breen C, Sarnak M, Siscovick D, Harris T, Cauley J, Newman AB, Robbins J. Association of kidney function with incident hip fracture in older adults. J Am Soc Nephrol. 2007 Jan;18(1):282-6. doi: 10.1681/ASN.2006050546. Epub 2006 Dec 13.

  PMID: 17167115 BACKGROUND

• Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP, Psaty BM, Newman AB. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis. 2004 May;43(5):861-7. doi: 10.1053/j.ajkd.2003.12.049.

  PMID: 15112177 BACKGROUND

• Kurella M, Chertow GM, Fried LF, Cummings SR, Harris T, Simonsick E, Satterfield S, Ayonayon H, Yaffe K. Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study. J Am Soc Nephrol. 2005 Jul;16(7):2127-33. doi: 10.1681/ASN.2005010005. Epub 2005 May 11.

  PMID: 15888561 BACKGROUND

• Molsted S, Prescott L, Heaf J, Eidemak I. Assessment and clinical aspects of health-related quality of life in dialysis patients and patients with chronic kidney disease. Nephron Clin Pract. 2007;106(1):c24-33. doi: 10.1159/000101481.

  PMID: 17409766 BACKGROUND

• Odden MC, Whooley MA, Shlipak MG. Depression, stress, and quality of life in persons with chronic kidney disease: the Heart and Soul Study. Nephron Clin Pract. 2006;103(1):c1-7. doi: 10.1159/000090112. Epub 2005 Dec 7.

  PMID: 16340237 BACKGROUND

• Hailpern SM, Melamed ML, Cohen HW, Hostetter TH. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol. 2007 Jul;18(7):2205-13. doi: 10.1681/ASN.2006101165. Epub 2007 Jun 6.

  PMID: 17554148 BACKGROUND

• King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.

  PMID: 24836312 BACKGROUND

• Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010 Feb;19(2):275-83. doi: 10.1517/13543780903501539.

  PMID: 20050822 BACKGROUND

• Sharma K, Ix JH, Mathew AV, Cho M, Pflueger A, Dunn SR, Francos B, Sharma S, Falkner B, McGowan TA, Donohue M, Ramachandrarao S, Xu R, Fervenza FC, Kopp JB. Pirfenidone for diabetic nephropathy. J Am Soc Nephrol. 2011 Jun;22(6):1144-51. doi: 10.1681/ASN.2010101049. Epub 2011 Apr 21.

  PMID: 21511828 BACKGROUND

• Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007 Sep;2(5):906-13. doi: 10.2215/CJN.01050207. Epub 2007 Aug 16.

  PMID: 17702727 BACKGROUND

• Kline JA, Jimenez D, Courtney DM, Ianus J, Cao L, Lensing AW, Prins MH, Wells PS. Comparison of Four Bleeding Risk Scores to Identify Rivaroxaban-treated Patients With Venous Thromboembolism at Low Risk for Major Bleeding. Acad Emerg Med. 2016 Feb;23(2):144-50. doi: 10.1111/acem.12865. Epub 2016 Jan 14.

  PMID: 26765080 BACKGROUND

• Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.

  PMID: 31085679 BACKGROUND

• Malhotra R, Craven T, Ambrosius WT, Killeen AA, Haley WE, Cheung AK, Chonchol M, Sarnak M, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT. Am J Kidney Dis. 2019 Jan;73(1):21-30. doi: 10.1053/j.ajkd.2018.07.015. Epub 2018 Oct 2.

  PMID: 30291012 BACKGROUND

• Ix JH, Biggs ML, Mukamal K, Djousse L, Siscovick D, Tracy R, Katz R, Delaney JA, Chaves P, Rifkin DE, Hughes-Austin JM, Garimella PS, Sarnak MJ, Shlipak MG, Kizer JR. Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study. J Am Soc Nephrol. 2015 Oct;26(10):2494-503. doi: 10.1681/ASN.2014070696. Epub 2015 Feb 5.

  PMID: 25655067 BACKGROUND

• Zhang WR, Craven TE, Malhotra R, Cheung AK, Chonchol M, Drawz P, Sarnak MJ, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Kidney Damage Biomarkers and Incident Chronic Kidney Disease During Blood Pressure Reduction: A Case-Control Study. Ann Intern Med. 2018 Nov 6;169(9):610-618. doi: 10.7326/M18-1037. Epub 2018 Oct 23.

  PMID: 30357395 BACKGROUND

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  PMID: 23112128 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Fibrosis; Cicatrix

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joachim H Ix, MD,MAS

  Veterans Medical Research Foundation at VASDHS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joachim H Ix, MD,MAS

CONTACT

858-552-8585; joeix@health.ucsd.edu

Erick O Castro, BS

CONTACT

858-552-8585; erick.castro@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Chief, Division of Nephrology-Hypertension, UCSD; Attending Physician VASDHS

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 6, 2020
• Study Start: October 26, 2020
• Primary Completion: May 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 27, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: We anticipate that the data and documentation will be provided to the NIDDK Data Repository when the study is complete (2024) and will become available approximately six months later.
• Access Criteria: Formal request to the NIDDK Central Repository

Locations

US (2)