A Phase 3 study of investigational drug ISIS 678354 administered under skin to patients with severely increased amount of triglycerides in blood.

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients with Severe Hypertriglyceridemia

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-002192-19-BG

Enrollment

450

Registered

2022-05-26

Start date

2022-08-23

Completion date

Unknown

Last updated

2024-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Severe hypertryglyceridemia MedDRA version: 20.0 Level: PT Classification code 10059183 Term: Familial hypertriglyceridaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: LLT Classification code 10020607 Term: Hyperchylomicronemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Interventions

Product Name: ISIS 678354 Product Code: ISIS 678354 Pharmaceutical Form: Solution for injection INN or Proposed INN: olezarsen Other descriptive name: ISIS 678354 sodium salt Concentration unit: mg/ml

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Fasting TG = 500 mg/dL (5.65 mmol/L) at Screening and Qualification - Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study. Other protocol defined criteria will apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 490 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

Exclusion criteria: • Hemoglobin A1c (HbA1c) = 9.5% at Screening • Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal • Total bilirubin > upper limit of normal unless due to Gilbert's syndrome • Estimated GFR < 40 mL/min/1.73 m^2 Other Protocol defined exclusion criteria will apply.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting TG from Baseline;Secondary Objective: To evaluate the efficacy of olezarsen as compared to placebo on: 1/ Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L) 2/ Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L) 3/ Proportion of patients who achieve fasting TG < 1000 mg/dL (11.29 mmol/L) 4/ Adjudicated acute pancreatitis event rate in patients with = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment 5/ Adjudicated acute pancreatitis event rate;Primary end point(s): The primary endpoint is the percent change in fasting TG from Baseline at Month 6 (average of Weeks 25 and 27) compared to placebo.;Timepoint(s) of evaluation of this end point: baseline, 6 months	—

Measure

Time frame

Main Objective: To evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting TG from Baseline;Secondary Objective: To evaluate the efficacy of olezarsen as compared to placebo on: 1/ Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L) 2/ Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L) 3/ Proportion of patients who achieve fasting TG < 1000 mg/dL (11.29 mmol/L) 4/ Adjudicated acute pancreatitis event rate in patients with = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment 5/ Adjudicated acute pancreatitis event rate;Primary end point(s): The primary endpoint is the percent change in fasting TG from Baseline at Month 6 (average of Weeks 25 and 27) compared to placebo.;Timepoint(s) of evaluation of this end point: baseline, 6 months

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Secondary

Measure	Time frame
Secondary end point(s): 1. Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo 2. Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo 3. Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 880 mg/dL 4. Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 1000 mg/dL 5. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo 6. Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo 7. Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo 8. Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo 9. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with = 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment 10. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo ;Timepoint(s) of evaluation of this end point: 1, 2) Baseline and Month 12 3, 4) Month 6 and 12 5, 6, 7, 8) Baseline, Month 6 and 12 9, 10) Week 1 through Week 53	—

Measure

Time frame

Secondary end point(s): 1. Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo 2. Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo 3. Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 880 mg/dL 4. Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 1000 mg/dL 5. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo 6. Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo 7. Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo 8. Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo 9. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with = 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment 10. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo ;Timepoint(s) of evaluation of this end point: 1, 2) Baseline and Month 12 3, 4) Month 6 and 12 5, 6, 7, 8) Baseline, Month 6 and 12 9, 10) Week 1 through Week 53

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Countries

Australia, Bulgaria, Canada, Czech Republic, Denmark, Finland, Hungary, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, Türkiye, United Kingdom, United States

Contacts

Public ContactStacy Woeppel

Ionis Pharmaceuticals, Inc.

globalregulatoryaffairs@ionisph.com1760 603-2346

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026