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

January 15, 2020 updated by: Ionis Pharmaceuticals, Inc.

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Ionis Investigational Site
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Ionis Investigational Site
  • Hungary
      • Budapest, Hungary, 1036
        • Ionis Investigational Site
      • Budapest, Hungary, 1083
        • Ionis Investigational Site
      • Budapest, Hungary, 1088
        • Ionis Investigational Site
      • Hatvan, Hungary, 3000
        • Ionis Investigational Site
      • Miskolc, Hungary, 3529
        • Ionis Investigational Site
      • Szekesfehervar, Hungary, 8000
        • Ionis Investigational Site
  • Poland
      • Bydgoszcz, Poland, 85-863
        • Ionis Investigational Site
      • Bytom, Poland, 41-902
        • Ionis Investigational Site
      • Chełm, Poland, 22-100
        • Ionis Investigational Site
      • Katowice, Poland, 40-752
        • Ionis Investigational Site
      • Kraków, Poland, 31-501
        • Ionis Investigational Site
      • Kraków, Poland, 31-530
        • Ionis Investigational Site
      • Mysłowice, Poland, 41-400
        • Ionis Investigational Site
      • Wierzchosławice, Poland, 33-122
        • Ionis Investigational Site
      • Wrocław, Poland, 50-127
        • Ionis Investigational Site
      • Wrocław, Poland, 50-220
        • Ionis Investigational Site
      • Wrocław, Poland, 50-349
        • Ionis Investigational Site
      • Łódź, Poland, 93-509
        • Ionis Investigational Site
  • United Kingdom
      • Dundee, United Kingdom, DD1 9SY
        • Ionis Investigational Site
      • Nottingham, United Kingdom, NG7 2UH
        • Ionis Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: IONIS DGAT2Rx
Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks
Drug: IONIS DGAT2Rx
Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks
Placebo Comparator: Placebo (sterile saline 0.9)
Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks
Drug: Placebo
Saline 0.9%

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Absolute Change in Liver Fat Percentage (Randomized Population)
Time Frame: Baseline to Week 15
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)
Time Frame: Baseline to Week 15
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
Time Frame: Up to 176 days
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
Time Frame: Up to 176 days
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change in Liver Fat Percentage
Time Frame: Baseline to Week 15
Relative percent change in liver fat percentage from baseline to post-treatment MRI.
Baseline to Week 15
Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage
Time Frame: Week 15
Percentage of participants with ≥ 30% relative reduction in liver fat percentage from baseline to post-treatment.
Week 15
Percent Change in Liver Volume
Time Frame: Baseline to Week 15
Assessed from Baseline MRI to Post-Treatment MRI.
Baseline to Week 15
Percent Change in Plasma Lipoprotein Profile
Time Frame: Week 15
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).
Week 15
Percent Change in Parameters of Insulin Resistance (IR)
Time Frame: Week 14
Percent change in parameters of IR (fasting plasma glucose [FPG], homeostatic model assessment - insulin resistance [HOMA-IR], and insulin) from baseline to post-treatment.
Week 14
Absolute Change in Hemoglobin A1C (HbA1C)
Time Frame: Week 14
Absolute change in HbA1C from baseline to post-treatment.
Week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Sanjay Bhanot, Ionis Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 3, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 28, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 28, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISIS 484137-CS2
  • 2017-003197-13 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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