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

Elevated Lipoprotein(a) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02414594
• Other study ID #: IONIS-APO(a)-LRx
• Status: Completed
• Phase: Phase 1
• Start date: April 2015
• Est. completion date: February 2016

Study information

• Verified date: December 2018
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Elevated Lipoprotein(a)

Intervention

Drug:
• IONIS-APO(a)-LRx
Ascending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection
• Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

Locations

Country	Name	City	State
Canada	Clinical Site	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.	Akcea Therapeutics

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 113 days
Primary	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.	Up to 113 days
Primary	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.	Up to 113 days
Secondary	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.	Up to 113 days
Secondary	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.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of IONIS-APO(a)-LRx on changes in Lp-PLA2 compared to baseline.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of IONIS-APO(a)-LRx on changes in sPLA2 compared to baseline.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of IONIS-APO(a)-LRx on changes in apo(a) isoform size compared to baseline.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of ISIS-APO(a)-LRx on changes in lipid panel compared to baseline.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of IONIS-APO(a)-LRx on changes in systemic markers of inflammation compared to baseline.	Up to 113 days
Secondary	Exploratory pharmacodynamic effects of IONIS-APO(a)-LRx	Effects of IONIS-APO(a)-LRx on changes in plasminogen/coagulation compared to baseline.	Up to 113 days