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Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Patients With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03385239
Recruitment Status : Active, not recruiting
First Posted : December 28, 2017
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Akcea Therapeutics

Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 678354 and to assess the efficacy of different doses and dosing regimens of ISIS 678354 for reduction of serum triglyceride (TG) levels in patients with hypertriglyceridemia and established CVD or at a high risk for CVD.

Condition or disease Intervention/treatment Phase
Hypertriglyceridemia Cardiovascular Diseases Drug: ISIS 678354 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 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
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Triglycerides

Arm Intervention/treatment
Experimental: ISIS 678354 Dose 1
Cohort A
Drug: ISIS 678354
Randomly assigned to one of the dosing cohorts
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx

Experimental: ISIS 678354 Dose 2
Cohort B
Drug: ISIS 678354
Randomly assigned to one of the dosing cohorts
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx

Experimental: ISIS 678354 Dose 3
Cohort C
Drug: ISIS 678354
Randomly assigned to one of the dosing cohorts
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx

Experimental: ISIS 678354 Dose 4
Cohort D
Drug: ISIS 678354
Randomly assigned to one of the dosing cohorts
Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx

Placebo Comparator: Placebo Comparator: Placebo: Sterile Normal Saline
Sterile Normal Saline (0.9% NaCl) by volume to match dose and regimen of active comparator depending on Cohort assignment
Drug: Placebo
Randomly assigned to one of the dosing cohorts. Dose of placebo in each cohort will match volume of active in that cohort.
Other Name: Sterile Normal Saline (0.9% NaCl)




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Clinical diagnosis of CVD (defined as documented coronary artery disease, stroke, or peripheral artery disease
  • Fasting serum TG ≥ 200 mg/dL (≥ 2.3 mmol/L) and ≤ 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/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
  • Type 2 diabetes mellitus with any of the following:

    • Newly diagnosed within 12 weeks of screening
    • 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
  • BMI > 40 kg/m2

Information from the National Library of Medicine

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


Locations
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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
Clinical Site
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
Sponsors and Collaborators
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.

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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: February 17, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Akcea Therapeutics:
AKCEA-APOCIII-LRx
IONIS-APOCIII-LRx
Dyslipidemia
Metabolic Disease
Hyperlipidemia
Cardiac Disease
Lipid Metabolism Disorders
Triglycerides High
Vascular Diseases
Additional relevant MeSH terms:
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Hypertriglyceridemia
Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases