- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04536688
A Study of RGLS4326 in Patients With Autosomal Dominant Polycystic Kidney Disease
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
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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California
-
La Mesa, California, United States, 91942
- Balboa Nephrology Medical Group
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Los Angeles, California, United States, 90022
- Academic Medical Research Institute
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Connecticut
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New Haven, Connecticut, United States, 06510
- Yale Nephrology Clinical Research
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Florida
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Altamonte Springs, Florida, United States, 32701
- Accel Research Sites- Mid-Florida Kidney and Hypertension Care
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Kansas
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Kansas City, Kansas, United States, 66160
- University of Kansas Medical Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02111
- Tufts Medical Center
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Michigan
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Roseville, Michigan, United States, 48066
- St. Clair Nephrology Research
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Minnesota
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Rochester, Minnesota, United States, 55904
- Mayo Clinic
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Texas
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Dallas, Texas, United States, 75390
- UT Southwestern Medical Center
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San Antonio, Texas, United States, 78209
- ICON Early Phase Services
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Washington
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Seattle, Washington, United States, 98104
- Swedish Polycystic Kidney Disease Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
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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
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Changes in polycystin-1 (PC-1) and polycystin-2 (PC-2) protein levels in urinary exosomes from baseline to Day 44
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Baseline to Day 44
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in secondary biomarker levels from baseline
Time Frame: Baseline to Day 44
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Changes in neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in urine from baseline to Day 44
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Baseline to Day 44
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Pharmacokinetics (Cmax)
Time Frame: Baseline to Day 44
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Maximum concentration (Cmax) of RGLS4326 in plasma following RGLS4326 treatment
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Baseline to Day 44
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Pharmacokinetics (Tmax)
Time Frame: Baseline to Day 71
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Time to maximum concentration (Tmax) of RGLS4326 in plasma following RGLS4326 treatment
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Baseline to Day 71
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Pharmacokinetics (AUC)
Time Frame: Baseline to Day 71
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Area under the curve (AUC) of RGLS4326 in plasma following RGLS4326 treatment
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Baseline to Day 71
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Number of participants with anti-drug antibodies (ADAs)
Time Frame: Baseline to Day 71
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Incidence of ADAs following RGLS4326 treatment from baseline to Day 71
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Baseline to Day 71
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Titre of anti-drug antibodies (ADAs) in patients with ADAs
Time Frame: Baseline to Day 71
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Titre of ADAs following RGLS4326 treatment from baseline to Day 71
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Baseline to Day 71
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Safety profile
Time Frame: Baseline to Day 71
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Incidence of AEs, lab abnormalities, and ECG abnormalities following RGLS4326 treatment
|
Baseline to Day 71
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Karl Cremer, PharmD, Regulus Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urologic Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Joint Diseases
- Musculoskeletal Diseases
- Muscular Diseases
- Musculoskeletal Abnormalities
- Abnormalities, Multiple
- Kidney Diseases, Cystic
- Ciliopathies
- Kidney Diseases
- Polycystic Kidney Diseases
- Polycystic Kidney, Autosomal Dominant
- Arthrogryposis
Other Study ID Numbers
- RGLS4326-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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