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

NCT03334214 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ISIS 484137-CS22017-003197-13
• Study Type: interventional
• Target: 44
• Locations: 4 countries
• Sites: 22

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.

Conditions

Hepatic Steatosis

Keywords

Hepatic Steatosis; IONIS-DGAT2Rx; Type 2 Diabetes

Outcome Measures

Primary Outcomes (4)

• Absolute Change in Liver Fat Percentage (Randomized Population)

  Absolute change in liver fat percentage as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) from baseline to post-treatment MRI.

  Baseline to Week 15

• Absolute Change in Liver Fat Percentage (Per Protocol Population)

  Absolute change in liver fat percentage as quantified by MRI-PDFF from baseline to post-treatment MRI.

  Baseline to Week 15

• Percentage of Participants With Adverse Events That Were Related to Treatment With IONIS DGAT2Rx

  An adverse event (AE) is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product.

  Up to 176 days

• Percentage of Participants With Adverse Events, Graded by Severity, That Were Related to Treatment With IONIS DGAT2Rx

  AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, June 2010. Grades: mild - the event is easily tolerated by the participant and does not affect the participant's usual daily activities; moderate - the event causes the participant more discomfort and interrupts the participant's usual daily activities; severe - the event is incapacitating and causes considerable interference with the participant's usual daily activities.

  Up to 176 days

Secondary Outcomes (6)

• Percent Change in Liver Fat Percentage

  Baseline to Week 15

• Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage

  Week 15

• Percent Change in Liver Volume

  Baseline to Week 15

• Percent Change in Plasma Lipoprotein Profile

  Week 15

• Percent Change in Parameters of Insulin Resistance (IR)

  Week 14

Study Arms (2)

IONIS DGAT2Rx

EXPERIMENTAL

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

Drug: IONIS DGAT2Rx

Placebo (sterile saline 0.9)

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

IONIS DGAT2Rx DRUG

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

IONIS DGAT2Rx

Placebo DRUG

Saline 0.9%

Placebo (sterile saline 0.9)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Clinically-significant abnormalities in medical history or physical examination.
• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (22)

Ionis Investigational Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Ionis Investigational Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Ionis Investigational Site

Budapest, 1036, Hungary

Location

Ionis Investigational Site

Budapest, 1083, Hungary

Location

Ionis Investigational Site

Budapest, 1088, Hungary

Location

Ionis Investigational Site

Hatvan, 3000, Hungary

Location

Ionis Investigational Site

Miskolc, 3529, Hungary

Location

Ionis Investigational Site

Székesfehérvár, 8000, Hungary

Location

Ionis Investigational Site

Bydgoszcz, 85-863, Poland

Location

Ionis Investigational Site

Bytom, 41-902, Poland

Location

Ionis Investigational Site

Chełm, 22-100, Poland

Location

Ionis Investigational Site

Katowice, 40-752, Poland

Location

Ionis Investigational Site

Krakow, 31-501, Poland

Location

Ionis Investigational Site

Krakow, 31-530, Poland

Location

Ionis Investigational Site

Lodz, 93-509, Poland

Location

Ionis Investigational Site

Mysłowice, 41-400, Poland

Location

Ionis Investigational Site

Wierzchosławice, 33-122, Poland

Location

Ionis Investigational Site

Wroclaw, 50-127, Poland

Location

Ionis Investigational Site

Wroclaw, 50-220, Poland

Location

Ionis Investigational Site

Wroclaw, 50-349, Poland

Location

Ionis Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

Ionis Investigational Site

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32553151 DERIVED

MeSH Terms

Conditions

Fatty Liver; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

patients@ionisph.com

800-679-4747

Study Officials

• Sanjay Bhanot

  Ionis Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: November 7, 2017
• Study Start: November 3, 2017
• Primary Completion: November 28, 2018
• Study Completion: November 28, 2018
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); HU (6); PL (12); GB (2)