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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
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Akcea Therapeutics

Tracking Information
First Submitted Date  ICMJE December 1, 2017
First Posted Date  ICMJE December 28, 2017
Last Update Posted Date November 20, 2020
Actual Study Start Date  ICMJE January 5, 2018
Actual Primary Completion Date November 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)
Official Title  ICMJE 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
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 participants with hypertriglyceridemia and established CVD or at a high risk for CVD.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertriglyceridemia
  • Cardiovascular Diseases
Intervention  ICMJE
  • Drug: ISIS 678354
    ISIS 678354 solution for SC injection.
    Other Name: AKCEA-APOCIII-LRx, IONIS-APOCIII-LRx
  • Drug: Placebo
    Sterile Normal Saline (0.9% NaCl).
Study Arms  ICMJE
  • 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).
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: ISIS 678354
  • 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.
    Intervention: Drug: ISIS 678354
  • 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.
    Intervention: Drug: ISIS 678354
  • 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.
    Intervention: Drug: ISIS 678354
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 Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2020)
114
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2017)
100
Actual Study Completion Date  ICMJE February 25, 2020
Actual Primary Completion Date November 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03385239
Other Study ID Numbers  ICMJE ISIS 678354-CS2
Has Data Monitoring Committee Yes
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
Responsible Party Akcea Therapeutics
Study Sponsor  ICMJE Akcea Therapeutics
Collaborators  ICMJE Ionis Pharmaceuticals, Inc.
Investigators  ICMJE Not Provided
PRS Account Akcea Therapeutics
Verification Date November 2020

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