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Trial record 4 of 4 for:    AKCEA-ANGPTL3-Lrx

Study of ISIS 703802 in Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

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: NCT03371355
Recruitment Status : Completed
First Posted : December 13, 2017
Last Update Posted : March 13, 2020
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Akcea Therapeutics

Tracking Information
First Submitted Date  ICMJE November 27, 2017
First Posted Date  ICMJE December 13, 2017
Last Update Posted Date March 13, 2020
Actual Study Start Date  ICMJE December 18, 2017
Actual Primary Completion Date November 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Percent change in fasting TG level from Baseline at the primary analysis time point. [ Time Frame: 6 months ]
Analysis will be the pairwise comparison of percent change from Baseline to primary analysis time point in TG between ISIS 703802 treatment groups and pooled placebo group.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • The safety of ISIS 703802 by the incidence of treatment-emergent adverse events [ Time Frame: 6 months ]
    The safety of ISIS 703802 will be assessed by determining adverse effects by dose. Safety results in subjects dosed with ISIS 703802 will be compared with those from subjects dosed with placebo.
  • The effect of ISIS 703802 on changes from Baseline at End-of-Treatment on glucose metabolism [ Time Frame: 6 months ]
    Analysis will be the change at the primary analysis time point in blood glucose metabolism.
  • The effect of ISIS 703802 on changes from Baseline at End-of-Treatment lipid metabolism [ Time Frame: 6 months ]
    Analysis will be the change at the primary analysis time point in markers of lipid metabolism.
  • The effect of ISIS 703802 on changes from Baseline at End-of-Treatment on liver fat [ Time Frame: 6 months ]
    Analysis will be the change of hepatic fat fraction (HFF) by MRI-PDFF compared between each ISIS 703802 treatment groups and pooled. placebo group.
  • Plasma Cmax of ISIS 703802 across different doses and dose regimens [ Time Frame: 6 months ]
    Cmax of ISIS 703802 in plasma will be calculated for the treatment groups.
  • Plasma Tmax of ISIS 703802 across different doses and dose regimens [ Time Frame: 6 months ]
    Tmax of ISIS 703802 in plasma will be calculated for the treatment groups.
  • Plasma AUC values of ISIS 703802 across different doses and dose regimens [ Time Frame: 6 months ]
    Plasma AUC values of ISIS 703802 will be calculated for the treatment groups.
  • The effect of ISIS 703802 on changes from Baseline on biomarkers related to liver inflammation [ Time Frame: 6 months ]
    Absolute change in ALT and AST and various markers of liver inflammation and fibrosis will be compared between each ISIS 703802 treatment group and pooled placebo group.
  • The effect of ISIS 703802 on changes from Baseline on adipose tissue as related to body composition [ Time Frame: 6 months ]
    Absolute change in body composition as measured by single slice MRI of adipose tissue will be compared between each ISIS 703802 treatment group and pooled placebo group.
  • The effect of ISIS 703802 on changes from Baseline on WHR (waist-to-hip ratio) as related to body composition. [ Time Frame: 6 months ]
    Absolute change in Body composition as measured WHR (waist-to-hip ratio) will be compared between each ISIS 703802 treatment group and pooled placebo group.
  • The effect of ISIS 703802 on changes from Baseline on BMI (Body Mass Index) as related to body composition [ Time Frame: 6 months ]
    Absolute change in Body composition as measured by BMI will be compared between each ISIS 703802 treatment group and pooled placebo group.
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 703802 in Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Finding Study of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus (T2DM), and Nonalcoholic Fatty Liver Disease (NAFLD)
Brief Summary This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 703802 and to assess the efficacy of different doses and dosing regimens of ISIS 703802 on glucose and lipid metabolism, and liver fat in subjects with Hypertriglyceridemia, Type 2 Diabetes Mellitus (T2DM), and Nonalcoholic Fatty Liver Disease (NAFLD).
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
  • NAFLD
  • Diabetes Mellitus, Type 2
  • Hypertriglyceridemia
  • Fatty Liver, Nonalcoholic
Intervention  ICMJE
  • Drug: ISIS 703802
    Randomly assigned to one of the dosing cohorts.
    Other Name: AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx
  • 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)
Study Arms  ICMJE
  • Experimental: ISIS 703802 Dose 1
    Cohort A
    Intervention: Drug: ISIS 703802
  • Experimental: ISIS 703802 Dose 2
    Cohort B
    Intervention: Drug: ISIS 703802
  • Experimental: ISIS 703802 Dose 3
    Cohort C
    Intervention: Drug: ISIS 703802
  • 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
    Intervention: Drug: Placebo
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: March 12, 2020)
105
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
144
Actual Study Completion Date  ICMJE February 24, 2020
Actual Primary Completion Date November 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Plasma TG at Screening > 150 mg/dL and at qualification of > 150 mg/dL
  • Documented history of hepatic steatosis with baseline MRI indicating hepatic fat fraction (HFF) ≥ 10%
  • Diagnosis of Type 2 Diabetes Mellitus with Hemoglobin A1c > 6.5 and ≤ 10% at Screening
  • Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months prior to Screening
  • Body mass index between 27- 40 kg/m2, inclusive, at Screening

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Active chronic liver disease, alcoholic liver disease, Wilson's disease hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, known or suspected hepatocellular carcinoma, history of or planned liver transplant for end-stage liver disease of any etiology
  • Documented history of advanced liver fibrosis
  • History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy, or variceal bleeding
  • History of clinically significant acute cardiac event within 6 months before Screening
  • History of heart failure with NYHA greater than Class II
  • Use of Insulin or insulin analogs, GLP-1 agonists, and PPARᵞ agonists (pioglitazone or rosiglitazone)
  • Weight change > 5% within 3 months before Screening
  • Conditions contraindicated for MRI procedures including any metal implant (e.g., heart pacemaker, rods, screws, aneurysm clips)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 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 NCT03371355
Other Study ID Numbers  ICMJE ISIS 703802-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 Not Provided
Responsible Party Akcea Therapeutics
Study Sponsor  ICMJE Akcea Therapeutics
Collaborators  ICMJE Ionis Pharmaceuticals, Inc.
Investigators  ICMJE Not Provided
PRS Account Akcea Therapeutics
Verification Date March 2020

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