A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION547 Administered Subcutaneously to Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- ION547
- Conditions
- Healthy Volunteers
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Cmax: Maximum Observed Plasma Concentration of ION547
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of the antisense inhibitor ION547 administered subcutaneously (SC) in healthy participants.
Detailed Description
This is a Phase 1, double-blind, randomized, placebo-controlled, dose escalation study of ION547 in up to 76 participants. Participants will be randomized to receive single and multiple doses of ION547 or placebo SC. The maximum length of participation in the study will be approximately 34 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
- •Healthy males or females 18 to 65, inclusive, at the time of informed consent.
- •Satisfy the following:
- •a. Females: Women of childbearing potential are not allowed to participate in this study.
- •b. Males must be abstinent, surgically sterile (vasectomy with negative semen analysis at Follow-up, or a surgically sterile non-pregnant female partner) or if engaged in sexual relations with a woman of childbearing potential (WOCBP), participant is utilizing a highly effective contraceptive method
- •Body mass index (BMI) ≤ 35 kilograms per square meter (kg/m\^2).
Exclusion Criteria
- •Clinically significant abnormalities in medical history or physical examination.
- •Screening laboratory results as follows, or any other clinically significant (CS) abnormalities in screening laboratory values that would render a participant unsuitable for inclusion:
- •Urine protein/creatinine (P/C) ratio greater than or equal to (≥) 0.2 milligrams (mg)/mg.
- •Positive test (including trace) for blood on urinalysis.
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, and blood urea nitrogen (BUN) \> upper limit of normal (ULN).
- •Hemoglobin A1c (HbA1c) \> ULN
- •Platelet count \< lower limit of normal (LLN)
- •aPTT \> ULN
- •Evidence of uncorrected hypothyroidism or hyperthyroidism based on thyroid function results at Screening.
- •Uncontrolled hypertension (blood pressure \[BP\] \> 160/100 millimeters of mercury \[mmHg\]).
Arms & Interventions
ION547
Ascending single multiple doses of ION547 will be administered by SC injection.
Intervention: ION547
Placebo
Ascending single multiple doses of ION547-matching placebo will be administered by SC injection.
Intervention: Placebo
Outcomes
Primary Outcomes
Cmax: Maximum Observed Plasma Concentration of ION547
Time Frame: Up to Day 232
Change from Baseline in FXII Antigen Levels
Time Frame: Up to Day 232
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
Time Frame: Up to Day 232
Tmax: Time Taken to Reach Maximal Plasma Concentration of ION547
Time Frame: Up to Day 232
Change from Baseline in FXII Activity Levels
Time Frame: Up to Day 232
AUCt: Area Under the Plasma Concentration-time Curve From Time Zero to Time t for ION547
Time Frame: Up to Day 232
Urine 0-24 Hour (hr) Excretion of ION547
Time Frame: Up to 24 hours