Familial Hypercholesterolemia, Hypertriglyceridemia
Conditions
Keywords
ANGPTL-3
Brief summary
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.
Interventions
DRUGIONIS ANGPTL3-LRx
DRUGPlacebo
0.9%NaCl, water, riboflavin
Sponsors
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx. | 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. |
| Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels) | Up to Day 127 | Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic effects of IONIS ANGPTL3-LRx | Up to Day 127 | Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline. |
Countries
Canada
Outcome results
None listed