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Completed

NCT Number: NCT02414594

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

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

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Key information

Conditions

Elevated Lipoprotein(a)

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Site

Toronto, Ontario, M9L 3A2, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

IONIS-APO(a)-LRx

Drug

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

Primary outcomes

  1. 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)

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: Up to 113 days

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

Secondary outcomes

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

    Time frame: Up to 113 days

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

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

    Time frame: Up to 113 days

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

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

    Time frame: Up to 113 days

    Effects of IONIS-APO(a)-LRx on changes in Lp-PLA2 compared to baseline.

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

    Time frame: Up to 113 days

    Effects of IONIS-APO(a)-LRx on changes in sPLA2 compared to baseline.

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

    Time frame: Up to 113 days

    Effects of IONIS-APO(a)-LRx on changes in apo(a) isoform size compared to baseline.

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

    Time frame: Up to 113 days

    Effects of ISIS-APO(a)-LRx on changes in lipid panel compared to baseline.

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

    Time frame: Up to 113 days

    Effects of IONIS-APO(a)-LRx on changes in systemic markers of inflammation compared to baseline.

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

    Time frame: Up to 113 days

    Effects of IONIS-APO(a)-LRx on changes in plasminogen/coagulation compared to baseline.

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Collaborators

  • Akcea Therapeutics

Registry information

Official study 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)

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Apr 13, 2015
Registry last updated
Dec 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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