Bempedoic Acid Therapy for Polycystic Kidney Disease

NCT07282821 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00003795HT94252510293
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

Autosomal dominant polycystic kidney disease (ADPKD), the most commonly inherited kidney disease, is characterized by the development of cysts in the kidney that impair function. Of those affected, half will progress to end-stage kidney disease by age 60, requiring dialysis or kidney transplant. To date, no effective and safe therapies exist for this deadly disease. Tolvaptan (Tol), the only FDA-approved drug for treatment of ADPKD, has some benefit in slowing kidney disease progression, but Tol causes frequent urination and thirst and also injures the liver in a small number of patients. The investigators' goal, therefore, is to develop new strategies to treat ADPKD that are safe and tolerable. The development of cysts in ADPKD patients results from two main cellular processes. The first is cell growth with an increase in the number of kidney cells that make up the outer surface of the cyst. The second is an increase in fluid secretion into the cysts that develop. The investigators have shown that an enzyme, AMP-activated protein kinase (AMPK), when activated can inhibit both of those processes. Moreover, genetic mutations that cause ADPKD may alter the energy metabolism of the cell, which in turn inhibits AMPK activity. Bempedoic acid (BA), a medication that is FDA-approved for the treatment of individuals with high cholesterol and has a good safety record, activates AMPK. In addition to activating AMPK, BA inhibits a second enzyme called ATP-citrate lyase (ACLY), which is involved in cholesterol synthesis. ACLY has received growing attention as a novel target for cancer treatment. ACLY inhibition blocks increases of cell numbers by inhibiting the lipid synthesis that is required for creation of new cell membranes. This study will test whether targeting these pathways through treatment with BA will help reverse dysfunctional metabolism in individuals with ADPKD and slow disease progression. The investigators will test this using a phase 2 clinical trial in which 120 individuals with rapidly progressive ADPKD and an estimated glomerular filtration rate of 35 or greater will be treated with either BA or placebo (inactive look-alike pill) for two years. Participants on or off a stable dose of Tol will be included in the study. Participants will be recruited from the U. of Vermont, U. of Maryland, and Tufts University, which have active PKD clinics and are recognized by the PKD Foundation as Centers of Excellence. Through follow-up visits and lab work, the investigators will assess the safety and tolerability of BA in the participants as the primary outcomes. The secondary goals are to assess preliminary efficacy and effects of BA on quality of life in study participants. The growth of cysts results in increased volume or size of the kidneys and liver. Total and cyst volumes of the kidney and liver and visceral abdominal fat content via magnetic resonance imaging (MRI) will be measured to gauge the effectiveness of this drug. The investigators also predict that proteins and small molecules involved in regulating cell energy metabolism, inflammation, and injury, as well as proteins directly involved in AMPK and ACLY function, will be altered in ADPKD patients. Levels of these proteins and small molecules may then subsequently change with BA therapy. Exploratory, mechanistic goals of this study are to identify prognostic and predictive urinary biomarkers in study participants. Successful completion of this study would have a significant impact on individuals with ADPKD by laying the groundwork for a new treatment strategy as well as by providing a new way to help guide treatment decisions. In summary, the goals of this phase 2 randomized, double-blind, placebo-controlled clinical trial are to test the safety, tolerability and preliminary efficacy of the drug bempedoic acid, FDA-approved to lower cholesterol, when used in ADPKD patients.

Conditions

ADPKD (Autosomal Dominant Polycystic Kidney Disease)

Keywords

ADPKD; bempedoic acid; AMPK; ACLY; height-adjusted total kidney volume; biomarkers; MRI; urine; metabolism; tolvaptan

Outcome Measures

Primary Outcomes (2)

• Safety as defined by rate of serious adverse events and adverse events of special interest (e.g., hyperuricemia, gout, liver transaminitis, and worsening anemia).

  Safety will be assessed through ascertainment of symptoms, laboratory measures, vital signs and physical exam. Serious adverse events (SAE) will be collected that occur from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting one or more of the following criteria, resulting in: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug could result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol, or 6) Resulting in congenital anomaly. A hepatologist with experience in drug-related liver toxicity will serve as a medical monitor. Their role is to review cases in which there is a significant elevation in liver function tests after the start of study drug and to advise on further workup, if necessary, and participant management.

  From enrollment to the end of treatment at 24 months

• Drug tolerability as assessed by the proportion of participants still taking study drug at 24 months and adherence directly measured by pill counts.

  Drug tolerability will be assessed by the proportion tolerating and taking the prescribed dose of study drug at each time point as measured by pill counts, and by a "yes" response to the question "Can you tolerate this study drug for the rest of your life?".

  At 3, 6, 12, 18, and 24 months (at the end of treatment)

Secondary Outcomes (5)

• Preliminary efficacy as assessed by changes in estimated glomerular filtration rate (eGFR) over time

  At baseline, 0.5, 1.5, 3, 6, 9, 12, 15, 18, 21, and 24 months (end of study)

• Preliminary efficacy as assessed by changes in the MRI-derived imaging parameter of height-adjusted total kidney volume (htTKV) over time

  At baseline, 12 months and 24 months (end of study)

• Health-related quality of life as assessed by the validated ADPKD-IS (Impact Scale) survey in the ADPKD population

  At baseline, 3, 6, 12, 18, and 24 months (end of study)

• Health-related quality of life as assessed by the validated ADPKD-PDS (Pain and Discomfort Scale) survey in the ADPKD population

  At baseline, 3, 6, 12, 18, and 24 months (end of study)

• Health-related quality of life as assessed by the validated ADPKD-UIS (Urinary Impact Scale) survey in the ADPKD population

  At baseline, 3, 6, 12, 18, and 24 months (end of study)

Study Arms (2)

Over-encapsulated bempedoic acid 180 mg p.o. once daily

ACTIVE COMPARATOR

Drug: Bempedoic Acid 180 MG Oral Tablet

Matching over-encapsulated placebo pill given p.o. once daily

PLACEBO COMPARATOR

Drug: Placebo Capsule(s)

Interventions

Bempedoic Acid 180 MG Oral Tablet DRUG

Over-encapsulated active study drug

Also known as: Nexletol

Over-encapsulated bempedoic acid 180 mg p.o. once daily

Placebo Capsule(s) DRUG

Over-encapsulated placebo pill

Matching over-encapsulated placebo pill given p.o. once daily

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ADPKD patients as defined by Pei-Ravine criteria
• Age 18-60 years
• Mayo Imaging Classifications (MIC) 1C-1E or MIC 1B with defined eGFR decline \>3 ml/min/1.73m2/yr (estimated from serum creatinine using the CKD-Epi equation)
• Estimated glomerular filtration rate (eGFR) ≥35 ml/min/1.73m2 by CKD-Epi equation utilizing creatinine
• Fluent English-speaking
• Able to provide informed consent
• Patients with and without current tolvaptan use (prescribed by primary nephrologist) at a stable dose for ≥3 months

You may not qualify if:

• Estimated GFR\<35 ml/min/1.73m2 (estimated from serum creatinine using the CKD-Epi equation)
• Proteinuria \>500 mg/day
• Current bempedoic acid (BA) use or history of hypersensitivity to BA
• Diabetes (currently diagnosed, or fasting glucose \>125 mg/dL)
• Serum uric acid \>10 mg/dL or 1 or more acute gout flare within the prior year
• Known active hepatitis or abnormal baseline liver function tests (LFTs) which is defined for patients who are not taking concomitant tolvaptan as ALT, AST or direct bilirubin \>1.5X ULN (upper limits of normal), or, for patients taking tolvaptan, as an ALT, AST, or direct bilirubin \>ULN
• Known unstable cerebral aneurysm
• Active coronary artery disease, defined as presence of stable or unstable angina
• Systemic disease (other than hypertension) likely to contribute to kidney disease (e.g., lupus)
• Current use of simvastatin \>20 mg or pravastatin \>40 mg daily.
• Pregnancy or lactation
• Hemoglobin \<10 g/dL
• Implanted ferromagnetic objects
• Use of an investigational product within prior 30 days or 5 half-lives, whichever is longer

Sponsors & Collaborators

• Kenneth Hallows: lead
• University of Maryland, Baltimore County: collaborator
• Tufts Medical Center: collaborator
• University of Pittsburgh: collaborator
• University of Southern California: collaborator
• Biomedical Research Institute of New Mexico: collaborator

Study Sites (3)

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

Tufts University Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Related Publications (1)

• Hallows KR, Li H, Saitta B, Sepehr S, Huang P, Pham J, Wang J, Mancino V, Chung EJ, Pinkosky SL, Pastor-Soler NM. Beneficial effects of bempedoic acid treatment in polycystic kidney disease cells and mice. Front Mol Biosci. 2022 Nov 25;9:1001941. doi: 10.3389/fmolb.2022.1001941. eCollection 2022.

  PMID: 36504724 BACKGROUND

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; Tablets

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Kenneth R Hallows, MD, PhD, FASN

  University of Vermont

  PRINCIPAL INVESTIGATOR

• Stephen Seliger, MD

  University of Maryland

  PRINCIPAL INVESTIGATOR

• Dana Miskulin, MD

  Tufts University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charalett Diggs, RN, MSN

CONTACT

410-706-2122; charalett.diggs@som.umaryland.edu

Kenneth R Hallows, MD, PhD, FASN

CONTACT

802-847-3572; kenneth.hallows@med.uvm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Patrick Professor of Medicine and Network Division Chief of Nephrology

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 15, 2025
• Study Start (Estimated): July 27, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): February 28, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning at the time the primary publication of results has occurred with no specific end date.
• Access Criteria: At the conclusion of the study, any data coded with a number will be made available to qualified individuals within the scientific community who apply for data use through a website to be established at the time of publication of the primary study. Requests and applications for study data access will be reviewed by the BEAT-PKD Steering Committee composed of principal investigators and co-investigators of the various study sites.

Locations

US (3)