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

• Sponsor: Ionis Pharmaceuticals, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT05355402
• Collaborator: (none)
• Enrollment: 112
• Locations: 28
• Arms: 2
• Anticipated Duration (Months): 16.8
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo and the percentage of participants who achieve different thresholds in fasting TG. Another objective is 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).

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia; Atherosclerotic Cardiovascular Disease; Severe Hypertriglyceridemia	Drug: Olezarsen; Drug: Placebo	Phase 2

Detailed Description

This will be a multi-center, randomized, double-blind, placebo-controlled study in approximately 112 participants with hypertriglyceridemia and established or at increased risk for atherosclerotic cardiovascular disease, and/or with severe hypertriglyceridemia. The study will have an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment follow-up period.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 9, 2022
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Olezarsen Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 49 weeks.	Drug: Olezarsen; Olezarsen will be administered by SC injection.; Other Names: ISIS 678354 AKCEA-APOCIII-LRx
Placebo Comparator: Placebo Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.	Drug: Placebo; Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG) [Baseline and Month 6 (average of Weeks 25 and 27)]

Secondary Outcome Measures

1. Proportion of Participants with Baseline TG < 500 mg/dL (5.65 mmol/L) Who Achieve Fasting TG < 150 milligrams per deciliter (mg/dL) (1. 69 millimoles per liter [mmol/L]) at Month 6 [Baseline and Month 6]

2. Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12 [Baseline and Month 12]

3. Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL (5.65 mmol/L) at Month 6 [Baseline and Month 6]

4. Percent Change From Baseline at Months 6 and 12 in Fasting Apolipoprotein C-III (apoC-III) [Baseline, Months 6 and 12]

5. Percent Change From Baseline at Months 6 and 12 in Fasting Very Low-density Lipoprotein Cholesterol (VLDL-C) [Baseline, Months 6 and 12]

6. Percent Change From Baseline at Months 6 and 12 in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) [Baseline, Months 6 and 12]

7. Percent Change From Baseline at Months 6 and 12 in High-density Lipoprotein Cholesterol (HDL-C) [Baseline, Months 6 and 12]

8. Percent Change From Baseline at Months 6 and 12 in Apolipoprotein B (apoB) [Baseline, Months 6 and 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Aged ≥ 18 years at the time of informed consent

2. Fall into at least 1 of the following groups (a or b):

3. 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

4. Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L).

5. Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines.

6. Participants must be willing to comply with diet and lifestyle recommendations as able.

Exclusion Criteria:

1. Diabetes with any of the following:

2. Newly diagnosed within 12 weeks of screening

3. Hemoglobin A1C (HbA1c) ≥ 9.5% at Screening

4. Change in basal insulin regimen > 20% within 3 months prior to Screening

5. For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥ 3 episodes of severe hypoglycemia within 6 months prior to Screening

6. Acute coronary syndrome or stroke/transient ischemic attack (TIA) within 6 months prior to Screening

7. 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

8. Active pancreatitis within 4 weeks prior to Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trials Research	Lincoln	California	United States	95648
2	Catalina Research Institute, LLC	Montclair	California	United States	91763
3	Metabolic Institute of America	Tarzana	California	United States	91356
4	Excel Medical Clinical Trials, LLC	Boca Raton	Florida	United States	33434
5	De La Cruz Research Center	Miami	Florida	United States	33184
6	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
7	Suncoast Clinical Research, Inc.	Palm Harbor	Florida	United States	34684
8	Research Physicians Network Alliance	Winter Park	Florida	United States	32792
9	IACT Health	Columbus	Georgia	United States	31904
10	Evanston Premier Healthcare Research	Evanston	Illinois	United States	60201
11	Clinical Investigation Specialist	Gurnee	Illinois	United States	60031
12	Cardiovascular Research of Northwest Indiana	Munster	Indiana	United States	46321
13	West Broadway Clinic	Council Bluffs	Iowa	United States	51501
14	Louisville Metabolic and Atherosclerosis Research Center (L-MARC)	Louisville	Kentucky	United States	40213
15	Aa Mrc, Llc	Flint	Michigan	United States	48504
16	Clinical Research of South Nevada	Las Vegas	Nevada	United States	89121
17	Palm Research Center, Inc.	Las Vegas	Nevada	United States	89148
18	Green and Seidner Family Practice Associates	Lansdale	Pennsylvania	United States	19446
19	Main Street Physicians Care Waterway	Little River	South Carolina	United States	29566
20	Health Concepts	Rapid City	South Dakota	United States	57702
21	Affinity Health Corp.	Nashville	Tennessee	United States	37203
22	Tennessee Center for Clinical Trials	Tullahoma	Tennessee	United States	37388
23	Southern Endocrinology Associates	Mesquite	Texas	United States	75149
24	Manassas Clinical Research Center	Manassas	Virginia	United States	20110
25	York Clinical Research LLC	Norfolk	Virginia	United States	23504
26	Bluewater Clinical Research Group Inc	Sarnia	Ontario	Canada	N7t 4X3
27	Ecogene-21	Chicoutimi	Quebec	Canada	G7H 7K9
28	Clinique des Maladies Lipidiques de Quebec Inc.	Quebec		Canada	G1V 4W2

Sponsors and Collaborators

• Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05355402
• Other Study ID Numbers: ISIS 678354-CS8
• First Posted: May 2, 2022
• Last Update Posted: Aug 8, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis; Hypertriglyceridemia

Study Results

No Results Posted as of Aug 8, 2022