Clinical trial NCT05521191: A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autosomal Dominant Polycystic Kidney Disease
ADPKD
Polycystic Kidney, Autosomal Dominant
Lead sponsor: Regulus Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-30
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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. .
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of RGLS4829: Incidence of AEs
timeFrame: Baseline to Day 113
measure: Impact of RGLS8429 on ADPKD biomarkers
timeFrame: Baseline to Day 113
Secondary outcomes:
measure: Impact of RGLS8429 on height-adjusted total kidney volume (htTKV)
timeFrame: Baseline to Day 113
measure: Pharmacokinetic properties of RGLS8429: Cmax
timeFrame: Baseline to Day 113
measure: Pharmacokinetic properties of RGLS8429: Tmax
timeFrame: Baseline to Day 113
measure: Pharmacokinetic properties of RGLS8429: t½
timeFrame: Baseline to Day 113
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Centricity Research Phoenix Multispecialty
state: Arizona
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: New Haven
country: United States
facility: Yale Nephrology Outpatient Clinic
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic - Florida
state: Florida
city: Orlando
country: United States
facility: Elixia
state: Florida
city: Augusta
country: United States
facility: Southeastern Clinical Research Institute, LLC
state: Georgia
city: Boise
country: United States
facility: CARE Institute
state: Idaho
city: Chubbuck
country: United States
facility: CARE Institute
state: Idaho
city: Idaho Falls
country: United States
facility: The Idaho Kidney Institute
state: Idaho
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Jared Grantham Kidney Institute
state: Kansas
city: Wichita
country: United States
facility: Witchita Nephrology Group, PA
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland School of Medicine, Nephrology
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Roseville
country: United States
facility: St. Clair Nephrology Research
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Swedish Center for Comprehensive Care
state: Washington
Study officials:
affiliation: Regulus Therapeutics
name: Rekha Garg, MD
role: STUDY_DIRECTOR
References: