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

NCT ID: NCT02709850

Last Updated: 2020-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-06-26

Brief Summary

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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.

Detailed Description

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Conditions

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Hypertriglyceridemia Familial Hypercholesterolemia

Keywords

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ANGPTL-3

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cohorts A, D: Placebo

Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0.9%NaCl, water, riboflavin

Cohorts A, D: IONIS ANGPTL3-LRx 20 mg

Participants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts A, D: IONIS ANGPTL3-LRx 120 mg

Participants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts B, C: Placebo

Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0.9%NaCl, water, riboflavin

Cohorts B, C: IONIS ANGPTL3-LRx 40 mg

Participants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts B, C: IONIS ANGPTL3-LRx 80 mg

Participants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts AA-DD: Placebo

Participants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0.9%NaCl, water, riboflavin

Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg

Participants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg

Participants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg

Participants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg

Participants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks.

Group Type EXPERIMENTAL

IONIS ANGPTL3-LRx

Intervention Type DRUG

Interventions

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IONIS ANGPTL3-LRx

Intervention Type DRUG

Placebo

0.9%NaCl, water, riboflavin

Intervention Type DRUG

Other Intervention Names

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ISIS 703802

Eligibility Criteria

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Inclusion Criteria

* 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


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


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


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


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


* 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

* 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


* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Akcea Therapeutics

INDUSTRY

Sponsor Role collaborator

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Site

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Graham MJ, Lee RG, Brandt TA, Tai LJ, Fu W, Peralta R, Yu R, Hurh E, Paz E, McEvoy BW, Baker BF, Pham NC, Digenio A, Hughes SG, Geary RS, Witztum JL, Crooke RM, Tsimikas S. Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides. N Engl J Med. 2017 Jul 20;377(3):222-232. doi: 10.1056/NEJMoa1701329. Epub 2017 May 24.

Reference Type DERIVED
PMID: 28538111 (View on PubMed)

Other Identifiers

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2015-004003-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 703802-CS1

Identifier Type: -

Identifier Source: org_study_id