A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia

• ClinicalTrials.gov Identifier: NCT05552326
• Recruitment Status: Recruiting
• First Posted: September 23, 2022
• Last Update Posted: May 10, 2024
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: September 20, 2022
• First Posted Date: September 23, 2022
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: August 31, 2022
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 20, 2022): Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo [ Time Frame: Baseline and Month 6 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 26, 2023)

• Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo [ Time Frame: Baseline and Month 12 ]
• 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 [ Time Frame: Month 6 and Month 12 ]
• 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 [ Time Frame: Month 6 and Month 12 ]
• Percentage of Participants Achieving Fasting TG < 1000 mg/dL in Participants with Baseline TG ≥ 1000 mg [ Time Frame: Month 6 and Month 12 ]
• Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and Month 12 ]
• Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• 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 [ Time Frame: Week 1 through Week 53 ]
• Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment [ Time Frame: Week 13 through Week 53 ]
• Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo [ Time Frame: Week 1 through Week 53 ]
• Adjudicated Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo [ Time Frame: Week 13 through Week 53 ]

Original Secondary Outcome Measures (submitted: September 20, 2022)

• Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo [ Time Frame: Baseline and Month 12 ]
• 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 [ Time Frame: Month 6 and Month 12 ]
• 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 [ Time Frame: Month 6 and Month 12 ]
• Percentage of Participants Achieving Fasting TG < 1000 mg/dL in Participants with Baseline TG ≥ 1000 mg [ Time Frame: Month 6 and Month 12 ]
• Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and Month 12 ]
• Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
• 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 [ Time Frame: Week 1 through Week 53 ]
• Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo [ Time Frame: Week 1 through Week 53 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
• Brief Summary: The purpose of this study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Detailed Description

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study in up to approximately 390 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

The Screening Period was extended with no impact to overall study timelines. Endpoints added to provide assessment on the pancreatitis rate after olezarsen reaches steady state levels.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Severe Hypertriglyceridemia

Intervention

• Drug: Olezarsen
  Olezarsen will be administered by SC injection.
  Other Names:

  • ISIS 678354
  • AKCEA-APOCIII-LRx
• Drug: Placebo
  Olezarsen-matching placebo will be administered by SC injection.

Study Arms

• Experimental: Olezarsen
  Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
  Intervention: Drug: Olezarsen
• Placebo Comparator: Placebo
  Olezarsen-matching placebo will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 20, 2022): 390
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
2. Participants 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.
3. Participants must be willing to comply with diet and lifestyle recommendations as able.

Exclusion Criteria:

1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
2. Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
3. Total bilirubin > 1.5 ULN unless due to Gilbert's syndrome
4. Estimated GFR < 30 mL/min/1.73 m^2

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ionis Pharmaceuticals; 844-366-0213; ionisSHTG2study@clinicaltrialmedia.com

• Listed Location Countries: Argentina, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Greece, Hungary, India, Italy, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Slovakia, Spain, Sweden, Taiwan, United States

Administrative Information

• NCT Number: NCT05552326
• Other Study ID Numbers: ISIS 678354-CS6; 2022-501420-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ionis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ionis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ionis Pharmaceuticals, Inc.
• Verification Date: May 2024