Healthy Volunteers
Conditions
Keywords
RGLS8429, Autosomal Dominant Polycystic Kidney Disease, ADPKD
Brief summary
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
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.
Interventions
DRUGRGLS8429
solution for subcutaneous injection
DRUGPlacebo volume-matching RGLS8429 dose
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 will be a double-blinded, randomized, placebo-controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, 18 to 55 years of age 2. Body mass index (BMI) 18 to 35 kg/m2 3. Medically healthy, with no clinically significant medical history in the opinion of the Investigator 4. Estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 5. 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
1. Subject is mentally incapacitated or has significant emotional problems 2. 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 3. History or presence of alcoholism or drug abuse within the past 2 years prior to Screening 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | Baseline to Day 29 | Incidence and severity of adverse events after administration of RGLS8429 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT and Determination of MTD | Baseline to Day 29 | Identify dose limiting toxicity and the maximum tolerated dose after RGLS8429 administration |
| Plasma Half-life (T1/2) of RGLS8429 | Baseline to Day 15 | Measure plasma elimination half-life after RGLS8429 administration |
| Plasma Clearance of RGLS8429 | Baseline to Day 15 | Measure plasma clearance after RGLS8429 administration |
| Area Under the Plasma Concentration vs Time Curve (AUC) of RGLS8429 | Baseline to Day 15 | Measure area under the plasma concentration vs time curve after RGLS8429 administration |
| Amount of RGLS8429 Excreted in Urine | Baseline to 24-hour | Measure the amount of RGLS8429 excreted in urine after RGLS8429 administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RGLS8429, First Dose Level Eligible participants will receive subcutaneous injection of the first dose level RGLS8429.
RGLS8429: solution for subcutaneous injection | 6 |
| RGLS8429, Second Dose Level Eligible participants will receive subcutaneous injection of the second dose level RGLS8429.
RGLS8429: solution for subcutaneous injection | 6 |
| RGLS8429, Third Dose Level Eligible participants will receive subcutaneous injection of the third dose level RGLS8429.
RGLS8429: solution for subcutaneous injection | 6 |
| RGLS8429, Fourth Dose Level Eligible participants will receive subcutaneous injection of the fourth dose level RGLS8429.
RGLS8429: solution for subcutaneous injection | 6 |
| Matching Placebo Eligible participants will receive subcutaneous injection of the placebo volume-matching RGLS8429 dose.
Placebo volume-matching RGLS8429 dose: solution for subcutaneous injection | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | RGLS8429, First Dose Level | RGLS8429, Second Dose Level | RGLS8429, Third Dose Level | RGLS8429, Fourth Dose Level | Matching Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 32 Participants |
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 9.48 | 33.8 Years STANDARD_DEVIATION 6.68 | 34.2 Years STANDARD_DEVIATION 6.18 | 38.2 Years STANDARD_DEVIATION 9.28 | 43.9 Years STANDARD_DEVIATION 6.58 | 37.7 Years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 5 Participants | 2 Participants | 7 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 4 Participants | 5 Participants | 7 Participants | 26 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | 32 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants | 2 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 0 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 3 / 6 | 1 / 6 | 3 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Incidence of Adverse Events (AEs)
Incidence and severity of adverse events after administration of RGLS8429
Time frame: Baseline to Day 29
Population: Safety Population: all subjects who received a dose of study drug; subjects were analyzed based on treatment received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RGLS8429, First Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Grade 3, 4 or 5 treatment-emergent adverse events | 0 participants |
| RGLS8429, First Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Treatment-emergent adverse events leading to discontinuation | 0 participants |
| RGLS8429, First Dose Level | Incidence of Adverse Events (AEs) | Number of Subjects with Serious Adverse Events or deaths | 0 participants |
| RGLS8429, First Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with at least one treatment-emergent adverse event | 1 participants |
| RGLS8429, Second Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Grade 3, 4 or 5 treatment-emergent adverse events | 0 participants |
| RGLS8429, Second Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with at least one treatment-emergent adverse event | 1 participants |
| RGLS8429, Second Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Treatment-emergent adverse events leading to discontinuation | 0 participants |
| RGLS8429, Second Dose Level | Incidence of Adverse Events (AEs) | Number of Subjects with Serious Adverse Events or deaths | 0 participants |
| RGLS8429, Third Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with at least one treatment-emergent adverse event | 3 participants |
| RGLS8429, Third Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Treatment-emergent adverse events leading to discontinuation | 0 participants |
| RGLS8429, Third Dose Level | Incidence of Adverse Events (AEs) | Number of Subjects with Serious Adverse Events or deaths | 0 participants |
| RGLS8429, Third Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Grade 3, 4 or 5 treatment-emergent adverse events | 0 participants |
| RGLS8429, Fourth Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Grade 3, 4 or 5 treatment-emergent adverse events | 0 participants |
| RGLS8429, Fourth Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with Treatment-emergent adverse events leading to discontinuation | 0 participants |
| RGLS8429, Fourth Dose Level | Incidence of Adverse Events (AEs) | Number of subjects with at least one treatment-emergent adverse event | 1 participants |
| RGLS8429, Fourth Dose Level | Incidence of Adverse Events (AEs) | Number of Subjects with Serious Adverse Events or deaths | 0 participants |
| Matching Placebo | Incidence of Adverse Events (AEs) | Number of subjects with at least one treatment-emergent adverse event | 3 participants |
| Matching Placebo | Incidence of Adverse Events (AEs) | Number of Subjects with Serious Adverse Events or deaths | 0 participants |
| Matching Placebo | Incidence of Adverse Events (AEs) | Number of subjects with Treatment-emergent adverse events leading to discontinuation | 0 participants |
| Matching Placebo | Incidence of Adverse Events (AEs) | Number of subjects with Grade 3, 4 or 5 treatment-emergent adverse events | 0 participants |
Secondary
Amount of RGLS8429 Excreted in Urine
Measure the amount of RGLS8429 excreted in urine after RGLS8429 administration
Time frame: Baseline to 24-hour
Secondary
Area Under the Plasma Concentration vs Time Curve (AUC) of RGLS8429
Measure area under the plasma concentration vs time curve after RGLS8429 administration
Time frame: Baseline to Day 15
Secondary
Incidence of DLT and Determination of MTD
Identify dose limiting toxicity and the maximum tolerated dose after RGLS8429 administration
Time frame: Baseline to Day 29
Secondary
Plasma Clearance of RGLS8429
Measure plasma clearance after RGLS8429 administration
Time frame: Baseline to Day 15
Secondary
Plasma Half-life (T1/2) of RGLS8429
Measure plasma elimination half-life after RGLS8429 administration
Time frame: Baseline to Day 15