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

• ClinicalTrials.gov Identifier: NCT04568434
• Recruitment Status: Completed
• First Posted: September 29, 2020
• Last Update Posted: May 10, 2024
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: September 23, 2020
• First Posted Date: September 29, 2020
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: November 16, 2020
• Actual Primary Completion Date: July 14, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 23, 2020): Percent Change from Baseline in Fasting TG at 6 Months (average of Weeks 23, 25, and 27) compared to placebo [ Time Frame: Baseline and Month 6 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2024)

• 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 ]
• Percent Change in Fasting apoC-III from Baseline at 6 Months and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and Month 12 ]
• Change from Baseline in the Proportion of Participants who Achieve ≥ 40% Reduction in Fasting TG at 6 Months Compared to Placebo [ Time Frame: Baseline and Month 6 ]
• Percent Change from Baseline in Fasting Apolipoprotein B-48 (apoB-48) at 6 Months and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and Month 12 ]
• Percent Change in Fasting non-HDL-C from Baseline at 6 Months and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and Month 12 ]
• Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo in Patients with a History of Pancreatitis within 10 Years Prior to Screening [ Time Frame: Week 1 through Week 53 and Week 13 through Week 53 ]
• Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo [ Time Frame: Week 1 through Week 53 and Week 13 through Week 53 ]
• Change from Baseline in the Proportion of Participants Who Achieve ≥ 70% Reduction in Fasting TG at 6 Months Compared to Placebo [ Time Frame: Baseline and Month 6 ]
• Proportion of Participants Who Achieve Fasting TG ≤ 880 mg/dL at 6 Months Compared to Placebo [ Time Frame: Week 1 through Week 53 ]
• 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 and Week 13 through Week 53 ]
• Proportion of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 6 Months Compared to Placebo [ Time Frame: At Month 6 ]

Original Secondary Outcome Measures (submitted: September 23, 2020)

• 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 ]
• Change from Baseline in the Proportion of Participants who Achieve ≥ 40% Reduction in Fasting TG at 6 Months Compared to Placebo [ Time Frame: Baseline and Month 6 ]
• Percent Change form Baseline in Fasting Apolipoprotein B-48 (apoB-48) at 6 Months Compared to Placebo [ Time Frame: At Month 6 ]
• Proportion of Participants who Achieve Fasting TG ≤ 750 mg/dL at 6 Months compared to placebo [ Time Frame: At Month 6 ]
• 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 ]
• Change from Baseline in the Proportion of Participants who Achieve ≥ 70% Reduction in Fasting TG at 6 Months Compared to Placebo [ Time Frame: Baseline and Month 6 ]
• Proportion of Participants who Achieve Fasting TG ≤ 500 mg/dL at 6 Months Compared to Placebo [ Time Frame: At Month 6 ]

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

Descriptive Information

• Brief Title: A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
• Brief Summary: The purpose of the 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 multi-center, double-blind, Phase 3 study in up to 60 patients with FCS. Participants will be 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 is approximately 74 weeks, which includes 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 may have the option of enrolling in an open label extension study.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Familial Chylomicronemia Syndrome

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 SC injection from Week 1 through Week 49.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 5, 2022): 66
• Original Estimated Enrollment (submitted: September 23, 2020): 60
• Actual Study Completion Date: October 17, 2023
• Actual Primary Completion Date: July 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Hungary, Israel, Italy, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04568434
• Other Study ID Numbers: ISIS 678354-CS3; 2020-002536-67 ( 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
• Product Manufactured in and Exported from the U.S.: Yes

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