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

Phase 1

Recruiting

• Conditions: Autosomal Dominant Polycystic Kidney Disease; ADPKD; Polycystic Kidney, Autosomal Dominant
• Interventions: Drug: RGLS8429; Drug: Placebo

• Registration Number: NCT05521191
• Lead Sponsor: Regulus Therapeutics Inc.

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

Detailed Description

This is a randomized, double-blind, placebo-controlled multiple ascending dose and an open-label fixed-dose Phase 1b study consisting of two parts, Part A and Part B. In Part A, multiple ascending doses of RGLS8429 or placebo will be administered via subcutaneous injection to subjects with ADPKD to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of RGLS8429. In Part B, a fixed-dose of RGLS8429 will be administered via subcutaneous injection to subjects with ADPKD to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of RGLS8429.

Study Timeline

• Study First Submitted: 2022-08-24
• Study First Submitted QC: 2022-08-25
• Study First Posted: 2022-08-30
• Study Start: 2022-10-06
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-27
• Last Update Posted: 2024-04-30
• Primary Completion: 2025-04
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Male or female ADPKD patients, 18 to 70 years old
2. 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)
3. eGFR between 30 to 90 mL/min/1.73 m2
4. Body mass index (BMI) 18 to 35 kg/m2
5. Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol

Key

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Exclusion Criteria

1. Administration of tolvaptan in the 28 days before randomization
2. Subject is mentally incapacitated or has significant emotional problems
3. 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
4. History or presence of alcoholism or drug abuse within the past 2 years prior to screening
5. Only one kidney or kidney transplant recipient
6. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RGLS8429	RGLS8429	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
Open Label Fixed Dose RGLS8429	RGLS8429	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.
Placebo	Placebo	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

Primary Outcome Measures

Name	Time	Method
Impact of RGLS8429 on ADPKD biomarkers	Baseline to Day 113	Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers
Safety and tolerability of RGLS4829: Incidence of AEs	Baseline to Day 113	Incidence of adverse events over time

Secondary Outcome Measures

Name	Time	Method
Impact of RGLS8429 on height-adjusted total kidney volume (htTKV)	Baseline to Day 113	Change from baseline in htTKV
Pharmacokinetic properties of RGLS8429: t½	Baseline to Day 113	Half-life of RGLS8429 (t½)
Pharmacokinetic properties of RGLS8429: Cmax	Baseline to Day 113	Maximum observed concentration (Cmax) of RGLS8429
Pharmacokinetic properties of RGLS8429: Tmax	Baseline to Day 113	Time to maximum observed concentration (Tmax) of RGLS8429

Trial Locations

Locations (26)

Centricity Research Phoenix Multispecialty; 🇺🇸 Mesa, Arizona, United States

Academic Medical Research Institute; 🇺🇸 Los Angeles, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Research by Design, LLC; 🇺🇸 Chicago, Illinois, United States

St. Clair Nephrology Research; 🇺🇸 Roseville, Michigan, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Swedish Center for Comprehensive Care; 🇺🇸 Seattle, Washington, United States

Nevada Kidney Disease and Hypertension Centers; 🇺🇸 Las Vegas, Nevada, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Mayo Clinic - Rochester; 🇺🇸 Rochester, Minnesota, United States

University of Kansas Medical Center Jared Grantham Kidney Institute; 🇺🇸 Kansas City, Kansas, United States

National Institute of Clinical Research, Inc.; 🇺🇸 Garden Grove, California, United States

CARE Institute; 🇺🇸 Chubbuck, Idaho, United States

University of Maryland School of Medicine, Nephrology; 🇺🇸 Baltimore, Maryland, United States

Elixia; 🇺🇸 Orlando, Florida, United States

Witchita Nephrology Group, PA; 🇺🇸 Wichita, Kansas, United States

California Institute of Renal Research; 🇺🇸 La Mesa, California, United States

Amicis Research Center; 🇺🇸 Granada Hills, California, United States

Southeastern Clinical Research Institute, LLC; 🇺🇸 Augusta, Georgia, United States

Valiance Clinical Research; 🇺🇸 S. Gate, California, United States

Mayo Clinic - Florida; 🇺🇸 Jacksonville, Florida, United States

Horizon Research Group, LLC; 🇺🇸 Coral Gables, Florida, United States

Northeast Clinical Research Center; 🇺🇸 Bethlehem, Pennsylvania, United States

The Idaho Kidney Institute; 🇺🇸 Idaho Falls, Idaho, United States

Yale Nephrology Outpatient Clinic; 🇺🇸 New Haven, Connecticut, United States