Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia

November 17, 2020 updated by: Ionis Pharmaceuticals, Inc.

A Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ISIS 703802, Targeting ANGPTL3, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides and Subjects With Familial Hypercholesterolemia

The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS ANGPTL3-LRx (ISIS 703802) given to healthy volunteer subjects with elevated triglycerides and subjects with familial hypercholesterolemia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M9L 3A2
        • Clinical Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria for All Cohorts:

  • Must have given written informed consent and be able to comply with all study requirements
  • Males or females 18 to 65 years, inclusive, at the time of informed consent
  • Body Mass Index (BMI) ≤ 35.0 kg/m2
  • Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal.
  • Males must be surgically sterile, abstinent or using an acceptable contraceptive method

Inclusion criteria for Cohorts, A, D, and AA to DD only:

  • Fasting triglycerides (TG) ≥ 150 mg/dL at Screening
  • Fasting low density lipoprotein cholesterol (LDL-C) > 70 mg/dL at Screening

Inclusion criteria for Cohorts B and C only:

  • Fasting TG 90 - 150 mg/dL at Screening
  • Fasting LDL-C > 70 mg/dL at Screening

Inclusion Criteria for Cohort EE Only:

  • Homozygous FH diagnosis and fasting LDL-C ≥ 190 mg/dL (4.9 mmol/L)

Inclusion Criteria for Cohort FF Only:

  • Heterozygous FH diagnosis and fasting LDL-C ≥ 160 mg/dL (4.1 mmol/L)

Inclusion Criteria for Cohorts EE and FF Only:

  • Maximally tolerated stable LDL-C lowering agents (stable for at least 12 weeks)
  • On stable low-fat diet
  • Stable weight (± 4 kg) for ≥ 6 weeks prior to screening

Exclusion Criteria for All Cohorts:

  • Known history or positive test for Human Immunodeficiency Virus (HIV), Hepatitis C (HCV), or Hepatitis B (HBV)
  • Treatment with another Study Drug, biological agent, or device within one-month or 5-half-lives of screening
  • Regular use of alcohol within 6 months of screening
  • Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
  • Known contraindication and/or allergy to heparin
  • Smoking > 10 cigarettes a day
  • Considered unsuitable for inclusion by the Principal Investigator

Exclusion Criteria for Cohorts EE and FF:

  • Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to screening, or cerebrovascular accident within 24 weeks prior to screening. Participants with adequately treated stable angina, per Investigator assessment, may be included
  • Congestive heart failure defined by NYHA Classes III or IV
  • Type 2 diabetes mellitus (T2DM) with HbA1c > 8.0%
  • Prior treatment with gene therapy
  • Currently receiving apheresis treatments or last apheresis treatment was within 8 weeks of screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Cohorts A, D: Placebo
Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
Drug: Placebo
0.9%NaCl, water, riboflavin
Experimental: Cohorts A, D: IONIS ANGPTL3-LRx 20 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Experimental: Cohorts A, D: IONIS ANGPTL3-LRx 120 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Placebo Comparator: Cohorts B, C: Placebo
Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
Drug: Placebo
0.9%NaCl, water, riboflavin
Experimental: Cohorts B, C: IONIS ANGPTL3-LRx 40 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Experimental: Cohorts B, C: IONIS ANGPTL3-LRx 80 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Placebo Comparator: Cohorts AA-DD: Placebo
Participants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks.
Drug: Placebo
0.9%NaCl, water, riboflavin
Experimental: Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg
Participants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Experimental: Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg
Participants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Experimental: Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg
Participants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802
Experimental: Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg
Participants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks.
Drug: IONIS ANGPTL3-LRx
Other Names:
  • ISIS 703802

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
Time Frame: Up to Day 127
The safety and tolerability of IONIS ANGPTL3-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 ANGPTL3-LRx will be compared with those from subjects dosed with placebo.
Up to Day 127
Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx.
Time Frame: Up to Day 127
The plasma pharmacokinetics (concentration-time results) of IONIS ANGPTL3-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of IONIS ANGPTL3-LRx excreted in urine at selected 24-hour intervals will also be determined.
Up to Day 127
Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels)
Time Frame: Up to Day 127
Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline.
Up to Day 127

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamic effects of IONIS ANGPTL3-LRx
Time Frame: Up to Day 127
Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline.
Up to Day 127

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Akcea Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 12, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 26, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 22, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISIS 703802-CS1
  • 2015-004003-23 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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