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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02414594
Recruitment Status : Completed
First Posted : April 13, 2015
Last Update Posted : December 5, 2018
Sponsor:
Collaborator:
Akcea Therapeutics
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Elevated Lipoprotein(a) Drug: IONIS-APO(a)-LRx Drug: Sterile Normal Saline (0.9% NaCl) Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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 Start Date : April 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016
Arms and Interventions
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Arm Intervention/treatment
Experimental: IONIS-APO(a)-LRx
Drug: IONIS-APO(a)-LRx
 Drug: IONIS-APO(a)-LRx
Ascending single and multiple doses of IONIS-APO(a)-LRx by subcutaneous (SC) injection
Placebo Comparator: Placebo (Normal Saline)
Drug: Sterile Normal Saline (0.9% NaCl)
 Drug: Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02414594


Locations
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Canada, Ontario
Clinical Site
Toronto, Ontario, Canada, M9L 3A2
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Akcea Therapeutics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02414594    
Other Study ID Numbers: IONIS-APO(a)-LRx
First Posted: April 13, 2015    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018