A Study of RGLS8429 in Healthy Volunteers

Study Overview
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Brief Summary
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Primary Objective • To assess the safety and tolerability of single ascending doses of RGLS8429 Secondary Objectives To identify dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) of a single SC dose of RGLS8429 To characterize the pharmacokinetic (PK) properties of RGLS8429

Detailed Description
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In this randomized, double-blind, placebo-controlled Phase 1 study, a single ascending dose of RGLS8429 or placebo will be administered via subcutaneous (SC) injection to healthy volunteers to evaluate the safety, tolerability, and PK of RGLS8429.

Official Title
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A Phase 1, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of RGLS8429

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: RGLS8429
* Drug: Placebo volume-matching RGLS8429 dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 55 years of age Body mass index (BMI) 18 to 35 kg/m2 Medically healthy, with no clinically significant medical history in the opinion of the Investigator Estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 Must understand and consent to the study procedures explained in the informed consent form (ICF) and be willing and able to comply with the protocol Exclusion Criteria: 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 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 and 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: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGLS8429, first dose level<br>Eligible participants will receive subcutaneous injection of the first dose level RGLS8429 or placebo | Drug: RGLS8429<br>* solution for subcutaneous injection<br>Drug: Placebo volume-matching RGLS8429 dose<br>* solution for subcutaneous injection<br>|
| Experimental: RGLS8429, second dose level<br>Eligible participants will receive subcutaneous injection of the second dose level RGLS8429 or placebo | Drug: RGLS8429<br>* solution for subcutaneous injection<br>Drug: Placebo volume-matching RGLS8429 dose<br>* solution for subcutaneous injection<br>|
| Experimental: RGLS8429, third dose level<br>Eligible participants will receive subcutaneous injection of the third dose level RGLS8429 or placebo | Drug: RGLS8429<br>* solution for subcutaneous injection<br>Drug: Placebo volume-matching RGLS8429 dose<br>* solution for subcutaneous injection<br>|
| Experimental: RGLS8429, fourth dose level<br>Eligible participants will receive subcutaneous injection of the fourth dose level RGLS8429 or placebo | Drug: RGLS8429<br>* solution for subcutaneous injection<br>Drug: Placebo volume-matching RGLS8429 dose<br>* solution for subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Incidence and severity of adverse events after administration of RGLS8429 | Baseline to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of DLT and determination of MTD | Identify dose limiting toxicity and the maximum tolerated dose after RGLS8429 administration | Baseline to Day 29 | 
| Plasma half-life (T1/2) of RGLS8429 | Measure plasma elimination half-life after RGLS8429 administration | Baseline to Day 15 | 
| Plasma clearance of RGLS8429 | Measure plasma clearance after RGLS8429 administration | Baseline to Day 15 | 
| Area under the plasma concentration vs time curve (AUC) of RGLS8429 | Measure area under the plasma concentration vs time curve after RGLS8429 administration | Baseline to Day 15 | 
| Amount of RGLS8429 excreted in urine | Measure the amount of RGLS8429 excreted in urine after RGLS8429 administration | Baseline to 24-hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RGLS8429, Autosomal Dominant Polycystic Kidney Disease, ADPKD