A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease

NCT05521191 | Completed Phase 1 FDA Drug

• 1 other identifier: RGLS8429-02
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 21

Brief Summary

Primary Objectives

• To assess the safety and tolerability of RGLS8429
• To assess the impact of RGLS8429 on ADPKD biomarkers Secondary Objectives
• To assess the impact of RGLS8429 on height-adjusted total kidney volume (htTKV)
• To characterize the pharmacokinetic (PK) properties of RGLS8429
• To assess the impact of RGLS8429 on renal function

Conditions

Autosomal Dominant Polycystic Kidney Disease; ADPKD; Polycystic Kidney, Autosomal Dominant

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of RGLS4829: Incidence of AEs

  Incidence of adverse events over time

  Baseline to Day 113

• Impact of RGLS8429 on ADPKD biomarkers

  Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers

  Baseline to Day 113

Secondary Outcomes (4)

• Impact of RGLS8429 on height-adjusted total kidney volume (htTKV)

  Baseline to Day 113

• Pharmacokinetic properties of RGLS8429: Cmax

  Baseline to Day 113

• Pharmacokinetic properties of RGLS8429: Tmax

  Baseline to Day 113

• Pharmacokinetic properties of RGLS8429: t½

  Baseline to Day 113

Study Arms (3)

RGLS8429

EXPERIMENTAL

The randomized,double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). * Cohort 1: first dose level of RGLS8429 or placebo * Cohort 2: second dose level of RGLS8429 or placebo * Cohort 3: third dose level of RGLS8429 or placebo

Drug: RGLS8429

Placebo

EXPERIMENTAL

The randomized double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). * Cohort 1: first dose level of RGLS8429 or placebo * Cohort 2: second dose level of RGLS8429 or placebo * Cohort 3: third dose level of RGLS8429 or placebo

Drug: Placebo

Open Label Fixed Dose RGLS8429

EXPERIMENTAL

The open-label fixed dose part of the study (Part B and Cohort 4) will consist of a single cohort of up to 30 subjects each receiving 300 mg RGLS8429.

Drug: RGLS8429

Interventions

RGLS8429 DRUG

Solution for subcutaneous injection

Open Label Fixed Dose RGLS8429; RGLS8429

Placebo DRUG

Solution for subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ADPKD patients, 18 to 70 years old
• Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon either the MRI obtained during screening, or a prior MRI obtained within 5 years of screening with documented Mayo classification)
• eGFR between 30 to 90 mL/min/1.73 m2
• Body mass index (BMI) 18 to 35 kg/m2
• Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol

You may not qualify if:

• Administration of tolvaptan in the 28 days before randomization
• Subject is mentally incapacitated or has significant emotional problems
• Any medical condition or social circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements; or may pose a risk to the subject's safety
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening
• Only one kidney or kidney transplant recipient
• Participation in another clinical trial and/or exposure to any investigational drug or approved therapy for investigational use within 28 days or 5 half-lives of the investigational drug's dosing, whichever is longer, prior to dosing. The 28-day or 5-half-life windows will be calculated from the date of the last dosing in the previous study to Day 1 of the current study.

Sponsors & Collaborators

• Regulus Therapeutics Inc.: lead

Study Sites (21)

Centricity Research Phoenix Multispecialty

Mesa, Arizona, 85206, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Yale Nephrology Outpatient Clinic

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic - Florida

Jacksonville, Florida, 32224, United States

Location

Elixia

Orlando, Florida, 32806, United States

Location

Southeastern Clinical Research Institute, LLC

Augusta, Georgia, 30904, United States

Location

CARE Institute

Boise, Idaho, 83706, United States

Location

CARE Institute

Chubbuck, Idaho, 83202, United States

Location

The Idaho Kidney Institute

Idaho Falls, Idaho, 83404, United States

Location

University of Chicago

Chicago, Illinois, 60617, United States

Location

Research by Design, LLC

Chicago, Illinois, 60643, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center Jared Grantham Kidney Institute

Kansas City, Kansas, 66160, United States

Location

Witchita Nephrology Group, PA

Wichita, Kansas, 67214, United States

Location

University of Maryland School of Medicine, Nephrology

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

St. Clair Nephrology Research

Roseville, Michigan, 48066, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Swedish Center for Comprehensive Care

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.

  PMID: 39331470 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

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

Study Officials

• Rekha Garg, MD

  Regulus Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study will have two parts. Part A is the double-blind, randomized, placebo-controlled study. Part B is the open-label fixed-dose study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will consist of two parts. Part A will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (approximately 36 subjects total). Part B will be an open-label fixed dose cohort of up to 30 subjects. .

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 30, 2022
• Study Start: October 6, 2022
• Primary Completion: January 27, 2025
• Study Completion: March 27, 2025
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)