Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS APO(a)-LRx in Healthy Volunteers With Elevated Lipoprotein(a)

Ionis Pharmaceuticals, Inc.60 enrolled

Overview

The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Elevated Lipoprotein(a)

Interventions

IONIS-APO(a)-LRxDRUG

Ascending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection

Sterile Normal Saline (0.9% NaCl)DRUG

Calculated volume to match active comparator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Must have given written informed consent and be able to comply with all study requirements * Healthy males or females aged 18-65 inclusive and weighing ≥ 50 kg at the time of informed consent * Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal * Males must be surgically sterile, abstinent or using an acceptable contraceptive method * BMI \< 35.0 kg/m2 * Subjects must have Lp(a) ≥ 75 nanomoles/liter nmol/L (30 mg/dL) at Screening Exclusion Criteria: * Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B * Treatment with another Study Drug, biological agent, or device within one-month of screening * Regular use of alcohol within 6 months of Screening * Use of concomitant drugs unless authorized by the Sponsor Medical Monitor * Smoking \> 10 cigarettes a day * Considered unsuitable for inclusion by the Principal Investigator

Locations (1)

Clinical Site

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

To evaluate the safety and tolerability of single and multiple doses of IONIS-APO(a)-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)

The safety and tolerability of IONIS-APO(a)-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS-APO(a)-LRx will be compared with those from subjects dosed with placebo.

Time frame: Up to 113 days

To evaluate the pharmacokinetics of single and multiple doses of IONIS-APO(a)-LRx (unconjugated and conjugated ASO)

The plasma pharmacokinetics of IONIS-APO(a)-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of ISIS-APO(a)-LRx excreted in urine at selected 24-hour intervals will also be determined.

Time frame: Up to 113 days

To evaluate the plasma pharmacodynamics of IONIS-APO(a)-LRx (Changes in plasma Lp(a) levels)

Changes in plasma Lp(a) levels compared to baseline.

Time frame: Up to 113 days

Secondary Outcomes

Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

Effects of IONIS-APO(a)-LRx on changes in levels of oxidized phospholipids associated with apoB-100 compared to baseline.

Time frame: Up to 113 days

Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

Effects of IONIS-APO(a)-LRx on changes in levels of oxidized phospholipids associated with apo(a) compared to baseline.

Time frame: Up to 113 days

Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.