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

NCT04536688 | Completed Phase 1 FDA Drug

• 1 other identifier: RGLS4326-03
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

Polycystic Kidney Disease, Autosomal Dominant

Outcome Measures

Primary Outcomes (1)

• Changes in primary biomarker levels from baseline

  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 Outcomes (7)

• Changes in secondary biomarker levels from baseline

  Baseline to Day 44

• Pharmacokinetics (Cmax)

  Baseline to Day 44

• Pharmacokinetics (Tmax)

  Baseline to Day 71

• Pharmacokinetics (AUC)

  Baseline to Day 71

• Number of participants with anti-drug antibodies (ADAs)

  Baseline to Day 71

Study Arms (3)

RGLS4326 1 mg/kg Q2W

EXPERIMENTAL

Eligible participants will receive subcutaneous injection of 1 mg/kg of RGLS4326 every other week for 4 doses

Drug: RGLS4326

RGLS4326 0.3 mg/kg Q2W

EXPERIMENTAL

Eligible participants will receive subcutaneous injection of 0.3 mg/kg of RGLS4326 every other week for 4 doses

Drug: RGLS4326

RGLS4326 0.1 or 0.5 mg/kg Q2W

EXPERIMENTAL

Eligible participants will receive subcutaneous injection of 0.1 or 0.5 mg/kg of RGLS4326 every other week for 4 doses

Drug: RGLS4326

Interventions

RGLS4326 DRUG

Solution for subcutaneous injection

RGLS4326 0.1 or 0.5 mg/kg Q2W; RGLS4326 0.3 mg/kg Q2W; RGLS4326 1 mg/kg Q2W

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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Regulus Therapeutics Inc.: lead

Study Sites (12)

Balboa Nephrology Medical Group

La Mesa, California, 91942, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Yale Nephrology Clinical Research

New Haven, Connecticut, 06510, United States

Location

Accel Research Sites- Mid-Florida Kidney and Hypertension Care

Altamonte Springs, Florida, 32701, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

St. Clair Nephrology Research

Roseville, Michigan, 48066, United States

Location

Mayo Clinic

Rochester, Minnesota, 55904, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

ICON Early Phase Services

San Antonio, Texas, 78209, United States

Location

Swedish Polycystic Kidney Disease Center

Seattle, Washington, 98104, United States

Location

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

• Karl Cremer, PharmD

  Regulus Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohorts will be enrolled and treated sequentially. Dosing decisions will be made based on prior cohort's safety and biomarker data. Six to 9 subjects will be enrolled in each cohort based on the magnitude and/or variability of the increase in PC1 and PC2 or to allow for replacement of subjects that do not complete the study. The highest dose (1 mg/kg) will be administered in cohort 1. If the Sponsor determines that the increase in PC1 and PC2 from baseline for cohort 1 is inadequate, the study may be stopped for futility. If the Sponsor determines that the increase from baseline for cohort 1 is adequate, then 0.3 mg/kg will be administered in cohort 2. Based on the increase of PC1 and PC2 from baseline in cohort 2, Sponsor may determine a higher dose needs to be evaluated, then 0.5 mg/kg will be administered in cohort 3. If the Sponsor determines that lower dose needs to be evaluated, then 0.1 mg/kg will be administered in cohort 3.

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: September 3, 2020
• Study Start: October 13, 2020
• Primary Completion: November 12, 2021
• Study Completion: November 12, 2021
• Last Updated: December 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)