Clinical trial NCT03334214: Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes
Official title: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Pharmacodynamics of ISIS 484137 (IONIS-DGAT2Rx, an Antisense Inhibitor of Diacylglycerol Acyltransferase 2) Administered Once-Weekly for 13 Weeks in Adult Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatic Steatosis
Keywords: Hepatic Steatosis
IONIS-DGAT2Rx
Type 2 Diabetes
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose is to assess the Safety, Tolerability, and Pharmacodynamics effect of IONIS DGAT2Rx in up to 45 Adult Patients with Type 2 Diabetes.

Detailed description: This short-term study will assess changes in hepatic steatosis over a 13-week treatment period in a patient population with higher risk for development of Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH), obese type 2 diabetes mellitus (T2DM) with elevated HbA1c.

Eligibility criteria: Inclusion Criteria:

* Must have given written informed consent and be able to comply with all study requirements.
* Males or females aged 18-75, inclusive, at the time of Informed Consent.
* Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal.
* Males must be surgically sterile, abstinent or using an acceptable contraceptive method.
* Body mass index (BMI) ≥ 27.0 - ≤ 39.0 kilograms per square meter (kg/m\^2).
* Diagnosis of Type 2 Diabetes Mellitus with an Hemoglobin A1C (HbA1c) ≥7.3% and ≤9.5% at screening.
* Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months prior to Screening.
* ≥ 10% liver fat prior to randomization assessed by MRI-PDFF.
* Stable body weight for at least 3 months before screening.

Exclusion Criteria:

* Clinically-significant abnormalities in medical history or physical examination.
* Clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion, per Sponsor.
* Evidence of uncorrected hypothyroidism or hyperthyroidism results at Screening.
* History of solid organ transplantation or renal dialysis.
* Clinically-significant complications of diabetes.
* Treatment with another Study Drug, biological agent, or device within one-month of screening.
* Known history or evidence of liver disease with a positive test for human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or chronic Hepatitis B virus (HBV), or chronic liver disease other than NASH.
* Recent history of, or current drug or alcohol abuse.
* Current use of concomitant medications known to significantly impact body weight or that may cause liver toxicity, per Investigator
* Use of anticoagulant/Antiplatelet agents unless the dose has been stable for 4 weeks prior to the first dose of study drug\]
* Use of non-steroidal anti-inflammatory drug nimesulide or any other drug influencing coagulation (except lose-dose aspirin).
* Use of obeticholic acid or ursodeoxycholic acid
* Considered unsuitable for inclusion by the Principal Investigator

Primary outcomes:
measure: Absolute Change in Liver Fat Percentage (Randomized Population)
timeFrame: Baseline to Week 15
measure: Absolute Change in Liver Fat Percentage (Per Protocol Population)
timeFrame: Baseline to Week 15
measure: Percentage of Participants With Adverse Events That Were Related to Treatment With IONIS DGAT2Rx
timeFrame: Up to 176 days
measure: Percentage of Participants With Adverse Events, Graded by Severity, That Were Related to Treatment With IONIS DGAT2Rx
timeFrame: Up to 176 days
Secondary outcomes:
measure: Percent Change in Liver Fat Percentage
timeFrame: Baseline to Week 15
measure: Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage
timeFrame: Week 15
measure: Percent Change in Liver Volume
timeFrame: Baseline to Week 15
measure: Percent Change in Plasma Lipoprotein Profile
timeFrame: Week 15
measure: Percent Change in Parameters of Insulin Resistance (IR)
timeFrame: Week 14
measure: Absolute Change in Hemoglobin A1C (HbA1C)
timeFrame: Week 14
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: Ionis Investigational Site
state: Nova Scotia
city: Chicoutimi
country: Canada
facility: Ionis Investigational Site
state: Quebec
city: Budapest
country: Hungary
facility: Ionis Investigational Site
city: Budapest
country: Hungary
facility: Ionis Investigational Site
city: Budapest
country: Hungary
facility: Ionis Investigational Site
city: Hatvan
country: Hungary
facility: Ionis Investigational Site
city: Miskolc
country: Hungary
facility: Ionis Investigational Site
city: Szekesfehervar
country: Hungary
facility: Ionis Investigational Site
city: Bydgoszcz
country: Poland
facility: Ionis Investigational Site
city: Bytom
country: Poland
facility: Ionis Investigational Site
city: Chełm
country: Poland
facility: Ionis Investigational Site
city: Katowice
country: Poland
facility: Ionis Investigational Site
city: Kraków
country: Poland
facility: Ionis Investigational Site
city: Kraków
country: Poland
facility: Ionis Investigational Site
city: Mysłowice
country: Poland
facility: Ionis Investigational Site
city: Wierzchosławice
country: Poland
facility: Ionis Investigational Site
city: Wrocław
country: Poland
facility: Ionis Investigational Site
city: Wrocław
country: Poland
facility: Ionis Investigational Site
city: Wrocław
country: Poland
facility: Ionis Investigational Site
city: Łódź
country: Poland
facility: Ionis Investigational Site
city: Dundee
country: United Kingdom
facility: Ionis Investigational Site
city: Nottingham
country: United Kingdom
facility: Ionis Investigational Site
Study officials:
affiliation: Ionis Pharmaceuticals, Inc.
name: Sanjay Bhanot
role: STUDY_DIRECTOR
References:
citation: Loomba R, Morgan E, Watts L, Xia S, Hannan LA, Geary RS, Baker BF, Bhanot S. Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2020 Sep;5(9):829-838. doi: 10.1016/S2468-1253(20)30186-2. Epub 2020 Jun 15.