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

A Blinded, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 681257 Administered Subcutaneously to Healthy Volunteers With Elevated Lipoprotein(a)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02414594

Enrollment

Registered

2015-04-13

Start date

2015-04-30

Completion date

2016-02-29

Last updated

2018-12-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Elevated Lipoprotein(a)

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.

Interventions

DRUGIONIS-APO(a)-LRx

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

DRUGSterile Normal Saline (0.9% NaCl)

Calculated volume to match active comparator

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Up to 113 days	Effects of IONIS-APO(a)-LRx on changes in levels of oxidized phospholipids associated with apoB-100 compared to baseline.

Countries

Canada

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 12, 2026