Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)
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ClinicalTrials.gov Identifier: NCT03385239 |
Recruitment Status :
Completed
First Posted : December 28, 2017
Last Update Posted : November 20, 2020
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Condition or disease | Intervention/treatment | Phase |
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Hypertriglyceridemia Cardiovascular Diseases | Drug: ISIS 678354 Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 114 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Phase 2 Study of ISIS 678354 Administered Subcutaneously to Patients With Hypertriglyceridemia and Established Cardiovascular Disease (CVD) or at a High Risk for CVD |
Actual Study Start Date : | January 5, 2018 |
Actual Primary Completion Date : | November 25, 2019 |
Actual Study Completion Date : | February 25, 2020 |

Arm | Intervention/treatment |
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Placebo Comparator: Pooled Placebo
Participants in each cohort (A,B,C and D) were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354).
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Drug: Placebo
Sterile Normal Saline (0.9% NaCl). |
Experimental: Cohort A: ISIS 678354: 10 mg Q4W
Cohort A participants received 10 milligrams (mg) ISIS 678354, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.
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Drug: ISIS 678354
ISIS 678354 solution for SC injection.
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx |
Experimental: Cohort C: ISIS 678354: 15 mg Q2W
Cohort C participants received 15 mg ISIS 678354, SC injection, once every 2 weeks (Q2W) for up to 51 weeks and a maximum of 26 doses.
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Drug: ISIS 678354
ISIS 678354 solution for SC injection.
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx |
Experimental: Cohort D: ISIS 678354: 10 mg QW
Cohort D participants received 10 mg ISIS 678354, SC injection, once weekly (QW) for up to 52 weeks and a maximum of 52 doses.
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Drug: ISIS 678354
ISIS 678354 solution for SC injection.
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx |
Placebo Comparator: Cohort B: ISIS 678354: 50 mg Q4W
Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses.
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Drug: ISIS 678354
ISIS 678354 solution for SC injection.
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx |
- Efficacy of different doses and dosing regimens of ISIS 678354 on the reduction in serum triglyceride (TG) levels from baseline at the primary analysis time point. [ Time Frame: 6 months ]The comparison of percent change from baseline to primary analysis time point in fasting serum TG levels between ISIS 678354 treated groups and pooled placebo group.
- The safety of ISIS 678354 by the incidence of treatment-emergent adverse events. [ Time Frame: 6 months and 12 months ]The safety of ISIS 678354 will be assessed by determining adverse effects by dose. Safety results in subjects dosed with ISIS 678354 will be compared with those from subjects dosed with placebo.
- Efficacy of different doses and dosing regimens of ISIS 678354 on serum triglyceride (TG) levels from baseline at the primary analysis time point. [ Time Frame: 6 months ]The comparison of the proportion of patients who achieve serum TG ≤ 150 mg/dL, and the proportion of patients achieving TG ≤ 100 mg/dL as compared to placebo at the primary analysis time point.
- To evaluate the efficacy of ISIS 678354 on serum levels of apolipoprotein C-III (apoC-III). [ Time Frame: 6 months ]Percent change from baseline at the primary analysis time point in apoCIII will be compared between each ISIS 678354 treatment groups and pooled placebo group.
- To evaluate the efficacy of ISIS 678354 on serum levels of cholesterol parameters. [ Time Frame: 6 months ]Percent change from baseline at the primary analysis time point in cholesterol parameters will be compared between each ISIS 678354 treatment groups and pooled placebo group.
- To evaluate the efficacy of ISIS 678354 on serum levels of apolipoprotein B100 (apoB). [ Time Frame: 6 months ]Percent change from baseline at the primary analysis time point in apoB will be compared between each ISIS 678354 treatment groups and pooled placebo group.
- To evaluate the efficacy of ISIS 678354 on serum levels of apolipoprotein A-1 (apoA-I). [ Time Frame: 6 months ]Percent change from baseline at the primary analysis time point in apoA-I will be compared between each ISIS 678354 treatment groups and pooled placebo group.
- Plasma Cmax of ISIS 678354 across different doses and dose regimens. [ Time Frame: 6 months ]Cmax of ISIS 678354 in plasma will be calculated for the treatment groups.
- Plasma Tmax of ISIS 678354 across different doses and dose regimens. [ Time Frame: 6 months ]Tmax of ISIS 678354 in plasma will be calculated for the treatment groups.
- Plasma AUC values of ISIS 678354 across different doses and dose regimens. [ Time Frame: 6 months ]Plasma AUC values of ISIS 678354 will be calculated for the treatment groups.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Clinical diagnosis of CVD (defined as documented coronary artery disease, stroke, or peripheral artery disease).
- Fasting serum triglycerides (TG) greater than or equal to (≥) 200 milligrams per deciliter (mg/dL) (≥ 2.3 millimoles per liter (mmol/L)) and less than or equal to (≤) 500 mg/dL (≥ 5.7 mmol/L) at Screening.
- Fasting TG ≥ 200 mg/dL and ≤ 500 mg/dL at Qualification visit.
- Must be on standard-of-care preventative therapy for known CVD risk factors.
Key Exclusion Criteria:
- Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/transient ischemic attack (TIA).
- Within 3 months of Screening: coronary, carotid, or peripheral arterial revascularization, major non-cardiac surgery, or lipoprotein apheresis.
- Heart failure New York Heart Association (NYHA) class IV.
- Type 1 diabetes mellitus.
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Type 2 diabetes mellitus with any of the following:
- Newly diagnosed within 12 weeks of Screening.
- Glycated hemoglobin (HbA1c) ≥ 9.0% at Screening.
- Recent change in anti-diabetic pharmacotherapy (change in dosage or addition of new medication within 12 weeks of Screening [with the exception of ± 10 units of insulin].
- Body Mass Index (BMI) greater than (>) 40 kilograms per square meter (kg/m^2).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03385239
United States, Arizona | |
Clinical Site | |
Cottonwood, Arizona, United States, 86326 | |
United States, Arkansas | |
Clinical Site | |
Little Rock, Arkansas, United States, 72205 | |
United States, California | |
Clinical Site | |
Carmichael, California, United States, 95608 | |
Clinical Site | |
Fresno, California, United States, 93720 | |
Clinical Site | |
La Jolla, California, United States, 92037-7410 | |
Clinical Site | |
Long Beach, California, United States, 90807 | |
Clinical Site | |
Montclair, California, United States, 91763 | |
United States, Delaware | |
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Wilmington, Delaware, United States, 19803 | |
United States, Florida | |
Clinical Site | |
Boca Raton, Florida, United States, 33434 | |
Clinical Site | |
Jacksonville, Florida, United States, 32216 | |
Clinical Site | |
New Port Richey, Florida, United States, 34652 | |
United States, Indiana | |
Clinical Site | |
Munster, Indiana, United States, 46321 | |
United States, Iowa | |
Clinical Site | |
Ames, Iowa, United States, 50010 | |
United States, Kansas | |
Clinical Site | |
Kansas City, Kansas, United States, 66160 | |
United States, Kentucky | |
Clinical Site | |
Louisville, Kentucky, United States, 40213 | |
United States, Massachusetts | |
Clinical Site | |
Fall River, Massachusetts, United States, 02721 | |
United States, New York | |
Clinical Site | |
Cooperstown, New York, United States, 13326 | |
United States, North Carolina | |
Clinical Site | |
High Point, North Carolina, United States, 27262 | |
United States, Oregon | |
Clinical Site | |
Portland, Oregon, United States, 97239 | |
United States, Pennsylvania | |
Clinical Site | |
Lansdale, Pennsylvania, United States, 19446 | |
United States, Rhode Island | |
Clinical Site | |
Providence, Rhode Island, United States, 02906 | |
United States, South Carolina | |
Clinical Site | |
Greer, South Carolina, United States, 29651 | |
United States, Texas | |
Clinical Site | |
Houston, Texas, United States, 77030 | |
United States, Wisconsin | |
Clinical Site | |
Milwaukee, Wisconsin, United States, 53215 | |
Canada, Ontario | |
Clinical Site | |
Cambridge, Ontario, Canada, N1R 6V6 | |
Clinical Site | |
Sudbury, Ontario, Canada, P3E 5M4 | |
Canada, Quebec | |
Clinical Site | |
Brossard, Quebec, Canada, J4Z 2K9 | |
Clinical Site | |
Chicoutimi, Quebec, Canada | |
Clinical Site | |
Gatineau, Quebec, Canada, J8Y 6S8 | |
Clinical Site | |
Montréal, Quebec, Canada, H1T 1C8 | |
Clinical Site | |
Québec, Quebec, Canada, G1V 4W2 |
Responsible Party: | Akcea Therapeutics |
ClinicalTrials.gov Identifier: | NCT03385239 |
Other Study ID Numbers: |
ISIS 678354-CS2 |
First Posted: | December 28, 2017 Key Record Dates |
Last Update Posted: | November 20, 2020 |
Last Verified: | November 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
AKCEA-APOCIII-LRx IONIS-APOCIII-LRx Dyslipidemia Metabolic Disease Hyperlipidemia |
Cardiac Disease Lipid Metabolism Disorders Triglycerides High Vascular Diseases |
Cardiovascular Diseases Hypertriglyceridemia Hyperlipidemias |
Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases |