search
Back to results

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

Primary Purpose

Hepatic Steatosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IONIS DGAT2Rx
Placebo
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Steatosis focused on measuring Hepatic Steatosis, IONIS-DGAT2Rx, Type 2 Diabetes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site
  • Ionis Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IONIS DGAT2Rx

Placebo (sterile saline 0.9)

Arm Description

Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Percent Change in Liver Fat Percentage
Relative percent change in liver fat percentage from baseline to post-treatment MRI.
Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage
Percentage of participants with ≥ 30% relative reduction in liver fat percentage from baseline to post-treatment.
Percent Change in Liver Volume
Assessed from Baseline MRI to Post-Treatment MRI.
Percent Change in Plasma Lipoprotein Profile
Percent change in plasma lipoprotein profile (total cholesterol, apolipoprotein B [ApoB], high density lipoprotein (HDL), low density lipoprotein cholesterol [LDL-C], non-HDL, triglycerides, and very low density lipoproteins [VLDL]) from baseline to the average of the post-treatment values assessed 1 and 2 weeks after the last dose (Post-Treatment 1 and Post-Treatment 2 visits).
Percent Change in Parameters of Insulin Resistance (IR)
Percent change in parameters of IR (fasting plasma glucose [FPG], homeostatic model assessment - insulin resistance [HOMA-IR], and insulin) from baseline to post-treatment.
Absolute Change in Hemoglobin A1C (HbA1C)
Absolute change in HbA1C from baseline to post-treatment.

Full Information

First Posted
October 23, 2017
Last Updated
January 15, 2020
Sponsor
Ionis Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03334214
Brief Title
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 3, 2017 (Actual)
Primary Completion Date
November 28, 2018 (Actual)
Study Completion Date
November 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Steatosis
Keywords
Hepatic Steatosis, IONIS-DGAT2Rx, Type 2 Diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IONIS DGAT2Rx
Arm Type
Experimental
Arm Description
Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks
Arm Title
Placebo (sterile saline 0.9)
Arm Type
Placebo Comparator
Arm Description
Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks
Intervention Type
Drug
Intervention Name(s)
IONIS DGAT2Rx
Intervention Description
Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Saline 0.9%
Primary Outcome Measure Information:
Title
Absolute Change in Liver Fat Percentage (Randomized Population)
Description
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.
Time Frame
Baseline to Week 15
Title
Absolute Change in Liver Fat Percentage (Per Protocol Population)
Description
Absolute change in liver fat percentage as quantified by MRI-PDFF from baseline to post-treatment MRI.
Time Frame
Baseline to Week 15
Title
Percentage of Participants With Adverse Events That Were Related to Treatment With IONIS DGAT2Rx
Description
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.
Time Frame
Up to 176 days
Title
Percentage of Participants With Adverse Events, Graded by Severity, That Were Related to Treatment With IONIS DGAT2Rx
Description
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.
Time Frame
Up to 176 days
Secondary Outcome Measure Information:
Title
Percent Change in Liver Fat Percentage
Description
Relative percent change in liver fat percentage from baseline to post-treatment MRI.
Time Frame
Baseline to Week 15
Title
Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage
Description
Percentage of participants with ≥ 30% relative reduction in liver fat percentage from baseline to post-treatment.
Time Frame
Week 15
Title
Percent Change in Liver Volume
Description
Assessed from Baseline MRI to Post-Treatment MRI.
Time Frame
Baseline to Week 15
Title
Percent Change in Plasma Lipoprotein Profile
Description
Percent change in plasma lipoprotein profile (total cholesterol, apolipoprotein B [ApoB], high density lipoprotein (HDL), low density lipoprotein cholesterol [LDL-C], non-HDL, triglycerides, and very low density lipoproteins [VLDL]) from baseline to the average of the post-treatment values assessed 1 and 2 weeks after the last dose (Post-Treatment 1 and Post-Treatment 2 visits).
Time Frame
Week 15
Title
Percent Change in Parameters of Insulin Resistance (IR)
Description
Percent change in parameters of IR (fasting plasma glucose [FPG], homeostatic model assessment - insulin resistance [HOMA-IR], and insulin) from baseline to post-treatment.
Time Frame
Week 14
Title
Absolute Change in Hemoglobin A1C (HbA1C)
Description
Absolute change in HbA1C from baseline to post-treatment.
Time Frame
Week 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanjay Bhanot
Organizational Affiliation
Ionis Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Ionis Investigational Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
Ionis Investigational Site
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Ionis Investigational Site
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Ionis Investigational Site
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Ionis Investigational Site
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Ionis Investigational Site
City
Hatvan
ZIP/Postal Code
3000
Country
Hungary
Facility Name
Ionis Investigational Site
City
Miskolc
ZIP/Postal Code
3529
Country
Hungary
Facility Name
Ionis Investigational Site
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Ionis Investigational Site
City
Bydgoszcz
ZIP/Postal Code
85-863
Country
Poland
Facility Name
Ionis Investigational Site
City
Bytom
ZIP/Postal Code
41-902
Country
Poland
Facility Name
Ionis Investigational Site
City
Chełm
ZIP/Postal Code
22-100
Country
Poland
Facility Name
Ionis Investigational Site
City
Katowice
ZIP/Postal Code
40-752
Country
Poland
Facility Name
Ionis Investigational Site
City
Kraków
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Ionis Investigational Site
City
Kraków
ZIP/Postal Code
31-530
Country
Poland
Facility Name
Ionis Investigational Site
City
Mysłowice
ZIP/Postal Code
41-400
Country
Poland
Facility Name
Ionis Investigational Site
City
Wierzchosławice
ZIP/Postal Code
33-122
Country
Poland
Facility Name
Ionis Investigational Site
City
Wrocław
ZIP/Postal Code
50-127
Country
Poland
Facility Name
Ionis Investigational Site
City
Wrocław
ZIP/Postal Code
50-220
Country
Poland
Facility Name
Ionis Investigational Site
City
Wrocław
ZIP/Postal Code
50-349
Country
Poland
Facility Name
Ionis Investigational Site
City
Łódź
ZIP/Postal Code
93-509
Country
Poland
Facility Name
Ionis Investigational Site
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
Ionis Investigational Site
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32553151
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs