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Trial of Pirfenidone to Prevent Progression of Chronic Kidney Disease (TOP-CKD)

Award Number: U01DK111510
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY / ABSTRACT Chronic kidney disease (CKD) is a global health problem, affecting more than half of adults over 70 years of age. Other than glycemic control in diabetes and use of angiotensin converting enzyme inhibitors, few specific therapies are available. Fibrosis is a dominant factor in the development and progression of nearly all forms of kidney diseases. Our group has led the development of non-invasive tests to evaluate the severity of fibrosis, in the absence of an invasive kidney biopsy, and we have experience leading clinical trials in CKD. Pirfenidone (Esbriet ®) is a first-in-class anti-fibrotic drug that is approved by the Food and Drug Administration (FDA) for treatment of idiopathic pulmonary fibrosis (IPF). In large-scale, phase 3 studies in IPF patients, pirfenidone showed substantial improvement in forced vital capacity, and significantly reduced the risk of death by 48%. Pharmacokinetic studies and pilot studies show that pirfenidone is safe in the setting of CKD, and have defined the dose of pirfenidone to maximize benefit and minimize side effects in CKD patients. Here, we propose a two-site, double-blind, placebo-controlled, phase 2b trial of pirfenidone 1335 mg/day vs. matched placebo in 160 CKD patients. In our first aim, we will determine the effect of pirfenidone on changes in renal fibrosis measured by diffusion-weighted magnetic resonance imaging (DW-MRI). In our second aim, we will determine the effect of pirfenidone on changes in urine biomarkers that are known to reflect the severity of fibrosis on biopsy, and are predictive of progressive loss of kidney function. Finally, prior anti-fibrotic trials in CKD patients lowered serum creatinine in early phase studies, but failed to prevent CKD progression events in phase 3 trials. The lowering of serum creatinine proved to be due to fluid retention rather than improvements in kidney function. To inform the most appropriate method to assess kidney function in a subsequent large- scale phase 3 trial, our 3rd Aim will determine whether the effect of pirfenidone on glomerular filtration rate (GFR) is similar when using measured glomerular filtration rate (GFR) by iohexol compared with GFR estimates obtained from serum creatinine or cystatin C. In the conduct of this trial, we will also obtain additional information about the safety and tolerability of pirfenidone in CKD. If successful, this study will lead directly to a large-scale, phase 3 trial evaluating pirfenidone for prevention of CKD progression in moderate-to- severe CKD. This project is ideally timed because of the combination of strong preliminary data, the FDA approval and widespread use of pirfenidone for IPF, and the enormous unmet need for new CKD treatments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $873,978 )
2023	2023	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/18/2023	SUPPLEMENT FOR EXPANSION	$349,999
2023	2023	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	8/17/2023	NON-COMPETING CONTINUATION	$523,979
														Subtotal = $873,978

Issue Date FY: 2022 ( Subtotal = $777,221 )
2022	2022	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	9/13/2022	SUPPLEMENT FOR EXPANSION	$200,000
2022	2022	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	9/8/2022	NON-COMPETING CONTINUATION	$577,221
														Subtotal = $777,221

Issue Date FY: 2021 ( Subtotal = $749,552 )
2021	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	3	9/10/2021	SUPPLEMENT FOR EXPANSION	$150,000
2021	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	9/1/2021	NON-COMPETING CONTINUATION	$599,552
2021	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/30/2021	NON-COMPETING CONTINUATION	$0
2021	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/1/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $749,552

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/21/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $652,305 )
2019	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	9/12/2019	NON-COMPETING CONTINUATION	$652,305
2019	2018	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/11/2019	NEW	$0
														Subtotal = $652,305

Issue Date FY: 2018 ( Subtotal = $666,605 )
2018	2018	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/12/2018	NEW	$666,605
														Subtotal = $666,605

Grand Total All Awards = $3,719,661

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Trial of Pirfenidone to Prevent Progression of Chronic Kidney Disease (TOP-CKD)

Award Number: U01DK111510

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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