Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes

NCT ID: NCT03334214

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-03
• Study Completion Date: 2018-11-28

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.

Conditions

Hepatic Steatosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IONIS DGAT2Rx

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

Group Type: EXPERIMENTAL

IONIS DGAT2Rx

Intervention Type: DRUG

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

Placebo (sterile saline 0.9)

Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline 0.9%

Interventions

IONIS DGAT2Rx

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

Intervention Type: DRUG

Placebo

Saline 0.9%

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sanjay Bhanot

Role: STUDY_DIRECTOR

Ionis Pharmaceuticals, Inc.

Locations

Ionis Investigational Site

Halifax, Nova Scotia, Canada

Ionis Investigational Site

Chicoutimi, Quebec, Canada

Ionis Investigational Site

Budapest, , Hungary

Ionis Investigational Site

Budapest, , Hungary

Ionis Investigational Site

Budapest, , Hungary

Ionis Investigational Site

Hatvan, , Hungary

Ionis Investigational Site

Miskolc, , Hungary

Ionis Investigational Site

Székesfehérvár, , Hungary

Ionis Investigational Site

Bydgoszcz, , Poland

Ionis Investigational Site

Bytom, , Poland

Ionis Investigational Site

Chełm, , Poland

Ionis Investigational Site

Katowice, , Poland

Ionis Investigational Site

Krakow, , Poland

Ionis Investigational Site

Krakow, , Poland

Ionis Investigational Site

Lodz, , Poland

Ionis Investigational Site

Mysłowice, , Poland

Ionis Investigational Site

Wierzchosławice, , Poland

Ionis Investigational Site

Wroclaw, , Poland

Ionis Investigational Site

Wroclaw, , Poland

Ionis Investigational Site

Wroclaw, , Poland

Ionis Investigational Site

Dundee, , United Kingdom

Ionis Investigational Site

Nottingham, , United Kingdom

Countries

Canada; Hungary; Poland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 32553151 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-003197-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 484137-CS2

Identifier Type: -

Identifier Source: org_study_id