HypertriglyceridemiaPhase 2NCT05355402
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia
A Phase 2 study testing Olezarsen in people with Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, run by Ionis Pharmaceuticals, Inc. at 24 sites in 2 countries.
Trial summary
The purpose of the study was to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12 and the proportion of participants who achieve different thresholds in fasting TG. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertriglyceridemia, Atherosclerotic Cardiovascular Disease, Severe Hypertriglyceridemia
- What is being tested?
- Olezarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 154 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 9 May 2022to 21 Dec 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 years at the time of informed consent
- Fall into at least 1 of the following groups (a or b):
- Hypertriglyceridemia with fasting TG ≥ 150 mg/dL (1.69 millimoles per liter [mmol/L]) and < 500 mg/dL (5.65 mmol/L) with either clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or at increased risk for ASCVD
- Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L).
- Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines.
- Participants must be willing to comply with diet and lifestyle recommendations as able.
Who cannot join
- Diabetes with any of the following:
- Newly diagnosed within 12 weeks of screening
- Hemoglobin A1C (HbA1c) ≥ 9.5% at Screening
- Change in basal insulin regimen > 20% within 3 months prior to Screening
- For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥ 3 episodes of severe hypoglycemia within 6 months prior to Screening
- Acute coronary syndrome or stroke/transient ischemic attack (TIA) within 6 months prior to Screening
- Major surgery, peripheral revascularization, or non-urgent percutaneous coronary intervention (PCI) within 3 months prior to Screening, or upcoming planned major surgery or major procedure (e.g., arterial revascularization) during the course of the study
- Active pancreatitis within 4 weeks prior to Screening
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States21 sites
Excel Medical Clinical Trials, LLC
Boca Raton, Florida, 33434
IACT Health
Columbus, Georgia, 31904
West Broadway Clinic
Council Bluffs, Iowa, 51501
Evanston Premier Healthcare Research
Evanston, Illinois, 60201
Aa Mrc, Llc
Flint, Michigan, 48504
Clinical Investigation Specialist
Gurnee, Illinois, 60031
Green and Seidner Family Practice Associates
Lansdale, Pennsylvania, 19446
Clinical Research of South Nevada
Las Vegas, Nevada, 89121
Palm Research Center, Inc.
Las Vegas, Nevada, 89148
Clinical Trials Research
Lincoln, California, 95648
Main Street Physicians Care Waterway
Little River, South Carolina, 29566
Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
Louisville, Kentucky, 40213
Manassas Clinical Research Center
Manassas, Virginia, 20110
Southern Endocrinology Associates
Mesquite, Texas, 75149
De La Cruz Research Center
Miami, Florida, 33184
Catalina Research Institute, LLC
Montclair, California, 91763
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652
York Clinical Research LLC
Norfolk, Virginia, 23504
Health Concepts
Rapid City, South Dakota, 57702
Tennessee Center for Clinical Trials
Tullahoma, Tennessee, 37388
Research Physicians Network Alliance
Winter Park, Florida, 32792
Canada3 sites
Ecogene-21
Chicoutimi, Quebec, G7H 7K9
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, G1V 4W2
Bluewater Clinical Research Group Inc
Sarnia, Ontario, N7t 4X3
About this study
Official title: A Randomized, Double-blind, Placebo-Controlled, Phase 2b Study of ISIS 678354 in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia
The purpose of the study was to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12 and the proportion of participants who achieve different thresholds in fasting TG. Other objectives were to evaluate the effect of olezarsen on percent change in fasting apolipoprotein C-III (apoC-III), very low-density lipoprotein cholesterol (VLDL-C), remnant cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, total cholesterol (TC), apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A-1 (apoA-1).
Read the detailed description
This was a multi-center, randomized, double-blind, placebo-controlled study in participants with hypertriglyceridemia (triglycerides > 150 milligrams per deciliter [mg/dL]) and established or at increased risk for atherosclerotic cardiovascular disease, and/or with severe hypertriglyceridemia. The study had an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment follow-up period.
- Being tested
- Olezarsen, Placebo
- Medical subject headings
- Hypertriglyceridemia, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlezarsenDrug
Also called ISIS 678354, AKCEA-APOCIII-LRx
SC injection.
PlaceboDrug
SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received olezarsen-matching placebo, as a single subcutaneous (SC) injection, once every 4 weeks for 53 weeks treatment period. Receives: Drug: Placebo |
| Olezarsen 50 mg | Experimental | Participants received olezarsen 50 mg, as a single 0.5 milliliters (mL) SC injection, once every 4 weeks for 53 weeks treatment period. Receives: Drug: Olezarsen |
| Olezarsen 80 mg | Experimental | Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period. Receives: Drug: Olezarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Fasting TG at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the jump to reference (J2R) approach.
Measured: Baseline, Month 6
Secondary outcomes (25)
Percent Change From Baseline in Fasting TG at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 Millimoles Per Liter [mmol/L]) at Month 6 With Baseline TG <500 mg/dL (5.65 mmol/L)
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 mmol/L) at Month 12 With Baseline TG <500 mg/dL (5.65 mmol/L)
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Apolipoprotein C-III (ApoC-III) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting ApoC-III at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Very Low-density Lipoprotein Cholesterol (VLDL-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in VLDL-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting Non-HDL-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting High-density Lipoprotein Cholesterol (HDL-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting HDL-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline Fasting Remnant Cholesterol (Remnant-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting Remnant-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting ApoB at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Apolipoprotein A-1 (ApoA-1) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting ApoA-1 at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting LDL-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Total Cholesterol (Total-C) at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percent Change From Baseline in Fasting Total-C at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 6
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 6
Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 12
Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.
Measured: Baseline, Month 12
Number of Participants With Adjudicated Acute Pancreatitis Events
All adverse events (AEs) and serious adverse events (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. Number of participants with adjudicated acute pancreatitis events were reported.
Measured: Up to 12 months
Number of Participants With Adjudicated Acute Pancreatitis Events (≥2 Events in 5 Years Prior to Enrollment)
The adjudicated acute pancreatitis event rates were compared between pooled olezarsen treatment and placebo group using a negative binomial regression model or Poisson regression model with the treatment group and natural log transformed baseline fasting TG as the factors, and number of adjudicated acute pancreatitis events in 5 years prior to enrollment as a covariate. The logarithm of time in year that each participant observed during the treatment period were used as an offset variable. Number of participants with adjudicated acute pancreatitis events with ≥2 events in 5 years prior to enrollment were reported.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2022
- Study start9 May 2022
- Primary completion22 Mar 2023
- Study completion21 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05355402
- Sponsor's protocol ID
- ISIS 678354-CS8
- Status last verified
- Apr 2026
- First submitted
- 26 Apr 2022
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Murphy SA, Goodrich EL, Zhang S, Gaudet D, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS; Bridge-TIMI 73a Investigators. Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk. N Engl J Med. 2024 May 16;390(19):1770-1780. doi: 10.1056/NEJMoa2402309. Epub 2024 Apr 7.
PubMed 38587249