A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)

Ionis Pharmaceuticals, Inc.66 enrolled

Overview

The purpose of the study was to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

This was a multi-center, double-blind, Phase 3 study in up to 60 patients with FCS. Participants were randomized in a 2:1 ratio to receive Olezarsen or matching placebo in a 53-week treatment period. The length of participation in the study was approximately 74 weeks, which included an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period. Following the treatment period, eligible patients had the option to enroll in the Open-label Extension (OLE) Study ISIS 678354-CS13 (NCT05130450).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Familial Chylomicronemia Syndrome

Interventions

OlezarsenDRUG

Olezarsen was administered by SC injection.

PlaceboDRUG

Olezarsen-matching placebo was administered by SC injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) * Fasting TG ≥ 880 mg/dL (10 millimoles per liter (mmol/L) at Screening * History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 35% * Stable doses of statins, omega-3 fatty acids, fibrates, or other lipid-lowering medications are allowed Key Exclusion Criteria: * Acute coronary syndrome within 6 months of Screening * Major surgery within 3 months of Screening * Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with participating in or completing the study

Locations (47)

Outcomes

Primary Outcomes

Percent Change From Baseline in Fasting TG at Month 6

Time frame: Baseline, Month 6

Secondary Outcomes

Percent Change From Baseline in Fasting TG at Month 12

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12

Time frame: Baseline, Months 6 and 12

Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6

Percentages are rounded off to the nearest single decimal place.

Time frame: Month 6

Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12

Time frame: Baseline, Months 6 and 12

Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12

Time frame: Baseline, Months 6 and 12

Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the Acute Pancreatitis Adjudication Committee (PAC) Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Time frame: During the treatment period Week 1 through Week 53

Data from ClinicalTrials.gov

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Diabetes/Lipid Management & Research Center

Huntington Beach, California, United States

University of California, San Francisco (UCSF) - Medical Center

San Francisco, California, United States

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

NorthShore University Health System

Evanston, Illinois, United States

Advocate Health and Hospitals Corporation - Lutheran General Hospital

Park Ridge, Illinois, United States

Ascension St. Vincent Cardiovascular Research Institute

Indianapolis, Indiana, United States

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, United States

University of Michigan- Endocrinology & Metabolism

Ann Arbor, Michigan, United States

New York University (NYU) Langone Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

...and 37 more locations

Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53)

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Time frame: During the treatment period Week 1 through Week 53

Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Time frame: Week 13 through Week 53

Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Time frame: Week 13 through Week 53

Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6

Percentages are rounded off to the nearest single decimal place.

Time frame: Month 6

Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6

Percentages are rounded off to the nearest single decimal place.

Time frame: Month 6

Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Time frame: During the treatment period Week 1 through Week 53

Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Time frame: Week 13 to Week 53

Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6

Percentages are rounded off to the nearest single decimal place.

Time frame: Month 6