This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05079919
Recruitment Status : Recruiting
First Posted : October 15, 2021
Last Update Posted : January 29, 2024
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 4, 2021
First Posted Date  ICMJE October 15, 2021
Last Update Posted Date January 29, 2024
Actual Study Start Date  ICMJE October 25, 2021
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 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  ICMJE
 (submitted: October 4, 2021)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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 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 12 ]
  • 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 [ 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 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 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  ICMJE
 (submitted: October 4, 2021)
  • 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 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 12 ]
  • 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 [ 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 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  ICMJE A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
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, randomized, double-blind, placebo-controlled study in up to approximately 540 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Severe Hypertriglyceridemia
Intervention  ICMJE
  • Drug: Olezarsen
    Olezarsen will be administered by SC injection.
    Other Names:
    • AKCEA-APOCIII-LRx
    • ISIS 678354
  • Drug: Placebo
    Olezarsen-matching placebo will be administered by SC injection.
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 9, 2022)
540
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2021)
450
Estimated Study Completion Date  ICMJE February 2025
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key 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.

Key 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 < 30 mL/min/1.73 m^2
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ionis Pharmaceuticals (844) 980-5110 ionisNCT05079919study@clinicaltrialmedia.com
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   New Zealand,   Norway,   Poland,   Portugal,   Slovakia,   South Africa,   Spain,   Sweden,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05079919
Other Study ID Numbers  ICMJE ISIS 678354-CS5
2021-002192-19 ( EudraCT Number )
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: No
Current Responsible Party Ionis Pharmaceuticals, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date January 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP