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

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

Official title:

A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose and an Open-Label Fixed-Dose Study in Patients With Autosomal Dominant Polycystic Kidney Disease to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of RGLS8429

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05521191
• Other study ID #: RGLS8429-02
• Status: Recruiting
• Phase: Phase 1
• Start date: October 6, 2022
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Regulus Therapeutics Inc.
• Contact: Kristen Gillotti
• Phone: 858-202-6300
• Email: kgillotti[@]regulusrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: June 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key 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 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.

Related Conditions & MeSH terms

• ADPKD
• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• RGLS8429
Solution for subcutaneous injection
• Placebo
Solution for subcutaneous injection

Locations

Country	Name	City	State
United States	Southeastern Clinical Research Institute, LLC	Augusta	Georgia
United States	University of Maryland School of Medicine, Nephrology	Baltimore	Maryland
United States	Northeast Clinical Research Center	Bethlehem	Pennsylvania
United States	Amicis Research Center	Beverly Hills	California
United States	CARE Institute	Boise	Idaho
United States	Tufts Medical Center	Boston	Massachusetts
United States	Research by Design, LLC	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	CARE Institute	Chubbuck	Idaho
United States	Horizon Research Group, LLC	Coral Gables	Florida
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Institute of Clinical Research, Inc.	Garden Grove	California
United States	Amicis Research Center	Granada Hills	California
United States	The Idaho Kidney Institute	Idaho Falls	Idaho
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic - Florida	Jacksonville	Florida
United States	University of Kansas Medical Center Jared Grantham Kidney Institute	Kansas City	Kansas
United States	California Institute of Renal Research	La Mesa	California
United States	Nevada Kidney Disease and Hypertension Centers	Las Vegas	Nevada
United States	Academic Medical Research Institute	Los Angeles	California
United States	Centricity Research Phoenix Multispecialty	Mesa	Arizona
United States	Yale Nephrology Outpatient Clinic	New Haven	Connecticut
United States	Elixia	Orlando	Florida
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	St. Clair Nephrology Research	Roseville	Michigan
United States	Valiance Clinical Research	S. Gate	California
United States	Swedish Center for Comprehensive Care	Seattle	Washington
United States	Witchita Nephrology Group, PA	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Regulus Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of RGLS4829: Incidence of AEs	Incidence of adverse events over time	Baseline to Day 113
Primary	Impact of RGLS8429 on ADPKD biomarkers	Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers	Baseline to Day 113
Secondary	Impact of RGLS8429 on height-adjusted total kidney volume (htTKV)	Change from baseline in htTKV	Baseline to Day 113
Secondary	Pharmacokinetic properties of RGLS8429: Cmax	Maximum observed concentration (Cmax) of RGLS8429	Baseline to Day 113
Secondary	Pharmacokinetic properties of RGLS8429: Tmax	Time to maximum observed concentration (Tmax) of RGLS8429	Baseline to Day 113
Secondary	Pharmacokinetic properties of RGLS8429: t½	Half-life of RGLS8429 (t½)	Baseline to Day 113