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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

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).

Condition or disease Intervention/treatment Phase
NAFLD Diabetes Mellitus, Type 2 Hypertriglyceridemia Fatty Liver, Nonalcoholic Drug: ISIS 703802 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : December 18, 2017
Actual Primary Completion Date : November 21, 2019
Actual Study Completion Date : February 24, 2020


Arm Intervention/treatment
Experimental: ISIS 703802 Dose 1
Cohort A
Drug: ISIS 703802
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx

Experimental: ISIS 703802 Dose 2
Cohort B
Drug: ISIS 703802
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx

Experimental: ISIS 703802 Dose 3
Cohort C
Drug: ISIS 703802
Randomly assigned to one of the dosing cohorts.
Other Name: AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx

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. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT03371355


Locations
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United States, Arizona
Clinical Sites
Chandler, Arizona, United States, 85224
Clinical Site
Fountain Hills, Arizona, United States, 85268
Clinical Site
Glendale, Arizona, United States, 85306
Clinical Site
Mesa, Arizona, United States, 85206
Clinical Site
Mesa, Arizona, United States, 85213
Clinical Site
Phoenix, Arizona, United States, 85020
Clinical Site
Phoenix, Arizona, United States, 85023
Clinical Site
Phoenix, Arizona, United States, 85050
United States, California
Clinical Site
Huntington Park, California, United States, 90255
Clinical Site
Los Angeles, California, United States, 90057
Clinical Site
Montclair, California, United States, 91710
Clinical Site
Panorama City, California, United States, 91402
Clinical Site
Poway, California, United States, 92064
United States, Florida
Clinical Site
Boca Raton, Florida, United States, 33487
Clinical Site
Jupiter, Florida, United States, 33458
Clinical Site
Miami, Florida, United States, 33165
Clinical Site
Port Saint Lucie, Florida, United States, 34952
United States, Georgia
Clinical Site
Atlanta, Georgia, United States, 30328
United States, Illinois
Clinical Site
Chicago, Illinois, United States, 60640
United States, Indiana
Clinical Site
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Clinical Site
Louisville, Kentucky, United States, 40213
United States, Minnesota
Clinical Site
Edina, Minnesota, United States, 55435
United States, New Jersey
Clinical Site
Bridgeton, New Jersey, United States, 08302
Clinical Site
Princeton, New Jersey, United States, 08540
United States, North Carolina
Clinical Site
Greensboro, North Carolina, United States, 27410
Clinical Site
High Point, North Carolina, United States, 27265
United States, Ohio
Clinical Site
Cincinnati, Ohio, United States, 45219
Clinical Site
Cincinnati, Ohio, United States, 45227
United States, South Carolina
Clinical Site
Charleston, South Carolina, United States, 29407
United States, Texas
Clinical Site
Austin, Texas, United States, 78735
Clinical Site
Carrollton, Texas, United States, 75010
Clinical Site
Dallas, Texas, United States, 75234
Clinical Site
Houston, Texas, United States, 77058
Clinical Site
Hurst, Texas, United States, 76054
Clinical Site
San Antonio, Texas, United States, 78215
Clinical Site
San Antonio, Texas, United States, 78229
United States, Utah
Clinical Site
Layton, Utah, United States, 84041
Canada, Ontario
Clinical Site
Hamilton, Ontario, Canada, L8L 5G8
Clinical Site
Toronto, Ontario, Canada, M3M 3E5
Canada, Quebec
Clinical Site
Chicoutimi, Quebec, Canada, G7H 7K9
Clinical Site
Montréal, Quebec, Canada, H4A 2C6
Sponsors and Collaborators
Akcea Therapeutics
Ionis Pharmaceuticals, Inc.

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Responsible Party: Akcea Therapeutics
ClinicalTrials.gov Identifier: NCT03371355    
Other Study ID Numbers: ISIS 703802-CS2
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: March 13, 2020
Last Verified: March 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-ANGPTL3-Lrx
Type 2 Diabetes
Hepatic Steatosis
Triglycerides
IONIS-ANGPTL3-Lrx
Fatty Liver
Fatty Liver Without Mention of Alcohol
Liver Fat
Liver Diseases
Diabetes Mellitus Type 2 in Nonobese
Diabetes Mellitus
Triglycerides High
High Triglycerides
Metabolic Disease
Endocrine System Diseases
Digestive System Disease
Glucose Metabolism Disorders
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertriglyceridemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Liver Extracts
Hematinics