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

Phase 1

Completed

• Conditions: Elevated Lipoprotein(a)
• Interventions: Drug: Sterile Normal Saline (0.9% NaCl); Drug: IONIS-APO(a)-LRx

• Registration Number: NCT02414594
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-04-07
• Study First Posted: 2015-04-13
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-03
• Last Update Posted: 2018-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo (Normal Saline)	Sterile Normal Saline (0.9% NaCl)	Drug: Sterile Normal Saline (0.9% NaCl)
IONIS-APO(a)-LRx	IONIS-APO(a)-LRx	Drug: IONIS-APO(a)-LRx

Primary Outcome Measures

Name	Time	Method
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)	Up to 113 days	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.
To evaluate the pharmacokinetics of single and multiple doses of IONIS-APO(a)-LRx (unconjugated and conjugated ASO)	Up to 113 days	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.
To evaluate the plasma pharmacodynamics of IONIS-APO(a)-LRx (Changes in plasma Lp(a) levels)	Up to 113 days	Changes in plasma Lp(a) levels compared to baseline.

Secondary Outcome Measures

Name	Time	Method
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Up to 113 days	Effects of IONIS-APO(a)-LRx on changes in plasminogen/coagulation compared to baseline.

Trial Locations

Locations (1)

Clinical Site; 🇨🇦 Toronto, Ontario, Canada