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

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