Phase 2
N=105
Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease
NAFLD · Diabetes Mellitus, Type 2 · Hypertriglyceridemia · Fatty Liver, Nonalcoholic
Bottom Line
View on ClinicalTrials.gov: NCT03371355 ↗Enrolled (actual)
105
Serious AEs
4.8%
Results posted
Feb 2021
Primary outcome: Primary: Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point — -16; -36; -53; -47 percent change — p=0.0343
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); ISIS 703802 40 mg (Drug); ISIS 703802 80 mg (Drug); ISIS 703802 20 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Akcea Therapeutics
- Primary completion
- Nov 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point |
-16; -36; -53; -47 | 0.0343 sig |
| SECONDARY Change From Baseline in Angiopoietin-Like 3 Protein at the Primary Analysis Time Point |
6.77; -43.11; -64.89; -52.98 | <0.0001 sig |
| SECONDARY Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point |
-4.8; -21.3; -41.9; -36.5; -2.5; 5.0 | 0.0327 sig |
| SECONDARY Change From Baseline in Free Fatty Acid (FFA) at Primary Analysis Time Point |
-0.0734; -0.0607; -0.0878; -0.0881 | 0.8299 |
| SECONDARY Change From Baseline in Lipoprotein(a) (Lp[a]) at the Primary Analysis Time Point |
-1.1; 6.8; 0.5; -2.8 | 0.0604 |
| SECONDARY Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point |
8; -41; -59; -54; -2; -11 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Plasma Glucose at the Primary Analysis Time Point |
-4.4; -21.6; 9.4; -2.2 | 0.1799 |
| SECONDARY Change From Baseline in Hemoglobin A1c (HbA1c) at the Primary Analysis Time Point |
0.19; -0.09; 0.26; 0.35 | 0.3995 |
| SECONDARY Change From Baseline in Fasting Insulin at the Primary Analysis Time Point |
-0.10; -1.48; -0.23; 3.48 | 0.7393 |
| SECONDARY Change From Baseline in and HOMA-IR at the Primary Analysis Time Point |
-0.119; -1.914; 0.141; 2.013 | 0.4710 |
| SECONDARY Change From Baseline in Fructosamine at Primary Analysis Time Point |
13.2; -10.0; 1.8; 15.1 | 0.0916 |
| SECONDARY Change From Baseline in Glycated Albumin at the Primary Analysis Time Point |
-0.0033; -0.0553; -0.0133; 0.0280 | 0.3202 |
| SECONDARY Change From Baseline in Weight at the Primary Analysis Time Point |
-1.00; -0.57; -0.99; -1.33 | 0.6157 |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point |
-1.66; 1.13; 0.42; -3.29; -2.35; 1.75 | 0.4431 |
| SECONDARY Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point |
-0.98; -0.40; -1.10; -1.38; -0.55; 1.80 | 0.5299 |
| SECONDARY Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point |
-1.69; -0.71; 2.39; -0.12 | 0.5752 |
| SECONDARY Percent Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point |
-7.09; 5.34; 18.94; 5.18 | 0.3023 |
| SECONDARY Percentage of Participants With HFF ≤ 8% by MRI-PDFF at the Primary Analysis Time Point |
16.0; 8.7; 4.5; 15.8 | — |
| SECONDARY Change From Baseline in Fatty Liver Index (FLI) at the Primary Analysis Time Point |
-3.50; -6.08; -9.21; -8.07 | 0.4583 |
| SECONDARY Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point |
-2.2; 4.8; 12.5; 6.6; -1.8; 3.2 | 0.1294 |
| SECONDARY Change From Baseline in Leptin at the Primary Analysis Time Point |
0.95; -0.24; -0.57; -3.23 | 0.4812 |
| SECONDARY Change From Baseline in Adiponectin at the Primary Analysis Time Point |
0.20; 0.05; -0.18; -0.18 | 0.6227 |
| SECONDARY Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint |
-25.61; -8.55; 7.31; -41.91; 14.83; 19.78 | 0.8591 |
| SECONDARY Change From Baseline in Waist Circumference by Single Slice MRI at the Primary Analysis Timepoint |
-2.25; -2.14; -2.95; -0.59 | 0.9734 |
| SECONDARY Change From Baseline in Waist to Hip Ratio (WHR) at the Primary Analysis Timepoint |
0.01; 0.01; -0.01; 0.01 | 0.8026 |
| SECONDARY Change From Baseline in Body Mass Index (BMI) at the Primary Analysis Timepoint |
-0.27; -0.17; -0.37; -0.50 | 0.7280 |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
18; 21; 24; 23 | — |
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 participants with hypertriglyceridemia, Type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD).
Eligibility Criteria
Key Inclusion Criteria
- Plasma triglycerides (TG) at Screening greater than (>)150 milligrams per deciliter (mg/dL) and at qualification of >150 mg/dL.
- Documented history of hepatic steatosis with baseline magnetic resonance imaging (MRI) indicating hepatic fat fraction (HFF) greater than (>) 8%.
- Diagnosis of Type 2 diabetes mellitus with hemoglobin A1c (HbA1c) >6.5 and less than or equal to (≤) 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 kilograms per meter square (kg/m^2), inclusive, at Screening.
Key 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 New York Heart Association (NYHA) greater than Class II.
- Use of Insulin or insulin analogs, glucagon-like peptide-1 (GLP-1) agonists, and peroxisome proliferator-activated receptor gamma (PPARᵞ) agonists (pioglitazone or rosiglitazone).
- Weight change >5% within 3 months before Screening.
- Conditions contraindicated for magnetic resonance imaging (MRI) procedures including any metal implant (example, heart pacemaker, rods, screws, aneurysm clips).
Data sourced from ClinicalTrials.gov (NCT03371355). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.