Clinical trial NCT02414594: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS APO(a)-LRx in Healthy Volunteers With Elevated Lipoprotein(a)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Elevated Lipoprotein(a)
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Akcea Therapeutics
First posted: 2015-04-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Up to 113 days
measure: To evaluate the pharmacokinetics of single and multiple doses of IONIS-APO(a)-LRx (unconjugated and conjugated ASO)
timeFrame: Up to 113 days
measure: To evaluate the plasma pharmacodynamics of IONIS-APO(a)-LRx (Changes in plasma Lp(a) levels)
timeFrame: Up to 113 days
Secondary outcomes:
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
measure: Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx
timeFrame: Up to 113 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Clinical Site
state: Ontario
Study officials:
References:
citation: Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, Marcovina SM, Hughes SG, Graham MJ, Crooke RM, Crooke ST, Witztum JL, Stroes ES, Tsimikas S. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016 Nov 5;388(10057):2239-2253. doi: 10.1016/S0140-6736(16)31009-1. Epub 2016 Sep 21.