ADPKD, Autosomal Dominant Polycystic Kidney Disease, Polycystic Kidney, Autosomal Dominant
Conditions
Brief summary
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
This is a randomized, double-blind, placebo-controlled multiple ascending dose and an open-label fixed-dose Phase 1b study consisting of two parts, Part A and Part B. In Part A, 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. In Part B, a fixed-dose of RGLS8429 will be administered via subcutaneous injection to subjects with ADPKD to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of RGLS8429.
Interventions
DRUGRGLS8429
Solution for subcutaneous injection
DRUGPlacebo
Solution for subcutaneous injection
Sponsors
Regulus Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study will have two parts. Part A is the double-blind, randomized, placebo-controlled study. Part B is the open-label fixed-dose study.
Intervention model description
The study will consist of two parts. Part A will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (approximately 36 subjects total). Part B will be an open-label fixed dose cohort of up to 30 subjects. .
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female ADPKD patients, 18 to 70 years old 2. 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) 3. eGFR between 30 to 90 mL/min/1.73 m2 4. Body mass index (BMI) 18 to 35 kg/m2 5. 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
1. Administration of tolvaptan in the 28 days before randomization 2. Subject is mentally incapacitated or has significant emotional problems 3. 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 4. History or presence of alcoholism or drug abuse within the past 2 years prior to screening 5. Only one kidney or kidney transplant recipient 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of RGLS4829: Incidence of AEs | Baseline to Day 113 | Incidence of adverse events over time |
| Impact of RGLS8429 on ADPKD biomarkers | Baseline to Day 113 | Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of RGLS8429 on height-adjusted total kidney volume (htTKV) | Baseline to Day 113 | Change from baseline in htTKV |
| Pharmacokinetic properties of RGLS8429: Cmax | Baseline to Day 113 | Maximum observed concentration (Cmax) of RGLS8429 |
| Pharmacokinetic properties of RGLS8429: Tmax | Baseline to Day 113 | Time to maximum observed concentration (Tmax) of RGLS8429 |
| Pharmacokinetic properties of RGLS8429: t½ | Baseline to Day 113 | Half-life of RGLS8429 (t½) |
Countries
United States
Outcome results
None listed