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HypertriglyceridemiaPhase 1NCT02709850

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

A Phase 1 study testing IONIS ANGPTL3-LRx in people with Hypertriglyceridemia and Familial Hypercholesterolemia, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
What is being tested?
IONIS ANGPTL3-LRx
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
1 siteCanada
Study dates
30 Nov 2015to 26 Jun 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Clinical Site

    Toronto, Ontario, M9L 3A2

Other trials in Canada

About this study

Official title: 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.

Being tested
IONIS ANGPTL3-LRx, Placebo
Keywords
ANGPTL-3
Medical subject headings
Hypertriglyceridemia, Hyperlipoproteinemia Type II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IONIS ANGPTL3-LRxDrug

    Also called ISIS 703802

  • PlaceboDrug

    0.9%NaCl, water, riboflavin

Study groups in NCT02709850
Study groupRoleWhat they receive
Cohorts A, D: PlaceboPlacebo comparatorParticipants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
Receives: Drug: Placebo
Cohorts A, D: IONIS ANGPTL3-LRx 20 mgExperimentalParticipants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts A, D: IONIS ANGPTL3-LRx 120 mgExperimentalParticipants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts B, C: PlaceboPlacebo comparatorParticipants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
Receives: Drug: Placebo
Cohorts B, C: IONIS ANGPTL3-LRx 40 mgExperimentalParticipants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts B, C: IONIS ANGPTL3-LRx 80 mgExperimentalParticipants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts AA-DD: PlaceboPlacebo comparatorParticipants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks.
Receives: Drug: Placebo
Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mgExperimentalParticipants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mgExperimentalParticipants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mgExperimentalParticipants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks.
Receives: Drug: IONIS ANGPTL3-LRx
Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mgExperimentalParticipants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks.
Receives: Drug: IONIS ANGPTL3-LRx

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    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.

    Measured: Up to Day 127

  2. Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx.

    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.

    Measured: Up to Day 127

  3. Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels)

    Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline.

    Measured: Up to Day 127

Secondary outcomes (1)

  1. Pharmacodynamic effects of IONIS ANGPTL3-LRx

    Effects of IONIS ANGPTL3-LRx on changes in ANGPTL3 plasma protein compared to baseline.

    Measured: Up to Day 127

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2016 (estimated)
  2. Study start30 Nov 2015
  3. Primary completion12 Apr 2017
  4. Study completion26 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02709850
Sponsor's protocol ID
ISIS 703802-CS1
Other IDs
2015-004003-23, 2015
Status last verified
Nov 2020
First submitted
22 Nov 2015
Last updated
19 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28538111

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IONIS ANGPTL3-LRx in people with Hypertriglyceridemia and Familial Hypercholesterolemia, run by Ionis Pharmaceuticals, Inc. at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02709850, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.

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