A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease

Study Overview
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Brief Summary
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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
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In this randomized, double-blind, placebo-controlled Phase 1b study, 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.

Official Title
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A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study in Patients With Autosomal Dominant Polycystic Kidney Disease to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of RGLS8429

Conditions
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Autosomal Dominant Polycystic Kidney Disease, ADPKD, Polycystic Kidney, Autosomal Dominant

Intervention / Treatment
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* Drug: RGLS8429
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female ADPKD patients, 18 to 70 years old 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) eGFR between 30 to 90 mL/min/1.73 m2 Body mass index (BMI) 18 to 35 kg/m2 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: Administration of tolvaptan in the 28 days before randomization Subject is mentally incapacitated or has significant emotional problems 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 History or presence of alcoholism or drug abuse within the past 2 years prior to screening Only one kidney or kidney transplant recipient 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will consist of three sequential cohorts of 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGLS8429<br>The study will consist of three sequential cohorts of 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). Cohort 1: first dose level of RGLS8429 or placebo Cohort 2: second dose level of RGLS8429 or placebo Cohort 3: third dose level of RGLS8429 or placebo | Drug: RGLS8429<br>* Solution for subcutaneous injection<br>|
| Experimental: Placebo<br>The study will consist of three sequential cohorts of 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). Cohort 1: first dose level of RGLS8429 or placebo Cohort 2: second dose level of RGLS8429 or placebo Cohort 3: third dose level of RGLS8429 or placebo | Drug: Placebo<br>* Solution for subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of RGLS4829: Incidence of AEs | Incidence of adverse events over time | Baseline to Day 113 | 
| Impact of RGLS8429 on ADPKD biomarkers | Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers | Baseline to Day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of RGLS8429 on height-adjusted total kidney volume (htTKV) | Change from baseline in htTKV | Baseline to Day 113 | 
| Pharmacokinetic properties of RGLS8429: Cmax | Maximum observed concentration (Cmax) of RGLS8429 | Baseline to Day 113 | 
| Pharmacokinetic properties of RGLS8429: Tmax | Time to maximum observed concentration (Tmax) of RGLS8429 | Baseline to Day 113 | 
| Pharmacokinetic properties of RGLS8429: t½ | Half-life of RGLS8429 (t½) | Baseline to Day 113 |