A Study of RGLS4326 in Patients With Autosomal Dominant Polycystic Kidney Disease

December 14, 2021 updated by: Regulus Therapeutics Inc.

A Phase 1b, Multicenter, Open-Label, Adaptive Design Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RGLS4326 Administered Via SC Injection to Patients With Autosomal Dominant Polycystic Kidney Disease

Primary Objective

• To assess the dose response relationship between RGLS4326 and ADPKD biomarkers

Secondary Objectives

  • To characterize the pharmacokinetic (PK) properties of RGLS4326 in plasma and urine
  • To assess the safety and tolerability of RGLS4326

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This is a Phase 1b, open-label, adaptive design dose-ranging study to evaluate ADPKD biomarkers, PK, safety, tolerability, and pharmacodynamics (PD) of RGLS4326 administered via SC injection to patients with ADPKD. The goal is to assess the dose response relationship between RGLS4326 and ADPKD biomarkers. The study will consist of three sequential cohorts with approximately 18 to 27 subjects total.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • La Mesa, California, United States, 91942
        • Balboa Nephrology Medical Group
      • Los Angeles, California, United States, 90022
        • Academic Medical Research Institute
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Nephrology Clinical Research
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • Accel Research Sites- Mid-Florida Kidney and Hypertension Care
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Michigan
      • Roseville, Michigan, United States, 48066
        • St. Clair Nephrology Research
    • Minnesota
      • Rochester, Minnesota, United States, 55904
        • Mayo Clinic
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78209
        • ICON Early Phase Services
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Polycystic Kidney Disease Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female ADPKD patients 18 to 70 years old
  • Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon prior MRI or CT Scan or MRI obtained during screening)
  • Estimated GFR at Screening between 30 to 90 mL/min/1.73 m^2 calculated by the investigator using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)
  • Body mass index (BMI) between 18 and 35 kg/m^2
  • If the patient has hypertension, the antihypertensive regimen must be stable for at least 28 days prior to randomization and the blood pressure adequately controlled prior to randomization
  • Female patients of childbearing potential must not be lactating and must have no plans to become pregnant during the course of the study through 28 days after the last dose of study drug. Female patients of childbearing potential who are heterosexual must agree to use one of the following methods of contraception considered to be highly effective (i.e., results in <1% failure rate when used consistently and correctly) from screening through 28 days after the last dose of study drug:

    • Intrauterine device (IUD) or intrauterine system (IUS) in place for at least 3 months prior to first dose
    • Partner has had a vasectomy. Vasectomy in the partner is only considered to be highly effective provided the partner is the sole sexual partner of the female patient of childbearing potential and the vasectomized partner has had a medical assessment of the surgical success.
    • Stable hormonal contraception associated with inhibition of ovulation (with approved oral, transdermal, or depot regimen) for at least 3 months prior to first dose
    • Bilateral tubal occlusion
  • Female patient of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose of study drug:

    • Hysterectomy
    • Bilateral oophorectomy
    • Bilateral tubal occlusion
    • Bilateral salpingectomy or be postmenopausal with no periods for at least 1 year prior to the first dose of study drug.
  • Male patients must agree to use a condom during heterosexual intercourse and to not have unprotected sexual intercourse with a female who is pregnant or breastfeeding from screening through 28 days after the last dose of study drug; and must agree to refrain from sperm donation for at least 90 days after the last dose of study drug
  • Screening hematology and clinical chemistries must meet the following criteria:

    • Platelets >150 x 10^9/L
    • Total white blood cell (WBC) count >3.0 x 10^9/L and absolute neutrophil count >1.5 x 10^9/L
    • Hemoglobin >12 g/dL for females and >13.5 g/dL for males
    • Total and direct bilirubin <1.5x upper limit of normal (ULN), unless elevated bilirubin is associated with a known benign condition (e.g., Gilbert's syndrome)
    • Alanine aminotransferase (ALT) <1.5x ULN
    • Aspartate aminotransferase (AST) <1.5x ULN
    • Alkaline phosphatase (ALP) <1.5x ULN
    • Gamma-glutamyl transferase (GGT) <2x ULN Note: At the discretion of the Investigator, screening laboratory testing may be repeated once to confirm out of range (exclusionary) results.
  • Able to understand all study procedures in the informed consent form (ICF) and willing to comply with all aspects of the protocol

Exclusion Criteria:

  • Administration of tolvaptan in the 28 days before randomization
  • Participation in another investigational interventional study within 28 days or 5 half-lives, whichever is longer, before randomization (e.g., bardoxolone, lixivaptan, tesevatinib, venglustat)
  • A history of drug and/or alcohol abuse within the past year
  • Active infection of the urinary tract (e.g., kidney, bladder, etc.)
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • Only one kidney or kidney transplant recipient.
  • Patient has concurrent medical condition (e.g., significant infection, other kidney disease, neurologic condition such as seizures, etc.) or social situation that may either present a safety risk or noncompliance with the study procedures
  • History of active malignancy within 5 years of randomization, except adequately treated basal cell or squamous cell carcinoma of the skin
  • History of a clinically significant reaction to an oligonucleotide compound
  • Significant blood loss or blood donation within the 28 days prior to randomization or plasma donation within 7 days prior to randomization
  • A tattoo or scarring on the abdomen or any other condition large enough to interfere with the ability to assess injection site reactions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RGLS4326 1 mg/kg Q2W
Eligible participants will receive subcutaneous injection of 1 mg/kg of RGLS4326 every other week for 4 doses
Solution for subcutaneous injection
Experimental: RGLS4326 0.3 mg/kg Q2W
Eligible participants will receive subcutaneous injection of 0.3 mg/kg of RGLS4326 every other week for 4 doses
Solution for subcutaneous injection
Experimental: RGLS4326 0.1 or 0.5 mg/kg Q2W
Eligible participants will receive subcutaneous injection of 0.1 or 0.5 mg/kg of RGLS4326 every other week for 4 doses
Solution for subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in primary biomarker levels from baseline
Time Frame: Baseline to Day 44
Changes in polycystin-1 (PC-1) and polycystin-2 (PC-2) protein levels in urinary exosomes from baseline to Day 44
Baseline to Day 44

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in secondary biomarker levels from baseline
Time Frame: Baseline to Day 44
Changes in neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in urine from baseline to Day 44
Baseline to Day 44
Pharmacokinetics (Cmax)
Time Frame: Baseline to Day 44
Maximum concentration (Cmax) of RGLS4326 in plasma following RGLS4326 treatment
Baseline to Day 44
Pharmacokinetics (Tmax)
Time Frame: Baseline to Day 71
Time to maximum concentration (Tmax) of RGLS4326 in plasma following RGLS4326 treatment
Baseline to Day 71
Pharmacokinetics (AUC)
Time Frame: Baseline to Day 71
Area under the curve (AUC) of RGLS4326 in plasma following RGLS4326 treatment
Baseline to Day 71
Number of participants with anti-drug antibodies (ADAs)
Time Frame: Baseline to Day 71
Incidence of ADAs following RGLS4326 treatment from baseline to Day 71
Baseline to Day 71
Titre of anti-drug antibodies (ADAs) in patients with ADAs
Time Frame: Baseline to Day 71
Titre of ADAs following RGLS4326 treatment from baseline to Day 71
Baseline to Day 71
Safety profile
Time Frame: Baseline to Day 71
Incidence of AEs, lab abnormalities, and ECG abnormalities following RGLS4326 treatment
Baseline to Day 71

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Karl Cremer, PharmD, Regulus Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 13, 2020

Primary Completion (Actual)

November 12, 2021

Study Completion (Actual)

November 12, 2021

Study Registration Dates

First Submitted

August 24, 2020

First Submitted That Met QC Criteria

August 28, 2020

First Posted (Actual)

September 3, 2020

Study Record Updates

Last Update Posted (Actual)

December 15, 2021

Last Update Submitted That Met QC Criteria

December 14, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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