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

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ClinicalTrials.gov Identifier: NCT03334214
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Hepatic Steatosis Drug: IONIS DGAT2Rx Drug: Placebo Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 3, 2017
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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%



Primary Outcome Measures :
  1. Incidence and severity of adverse events that are related to treatment with IONIS DGAT2Rx [ Time Frame: Up to 176 days ]
    The safety and tolerability of IONIS DGAT2Rx will be assessed by determining the incidence and severity of adverse events that are related to treatment with IONIS DGAT2Rx

  2. Absolute change in liver fat percentage [ Time Frame: Week 15 ]
    Absolute change in liver fat percentage as quantified by MRI-PDFF from Baseline to Post-Treatment MRI


Secondary Outcome Measures :
  1. Relative percent change in liver fat percentage [ Time Frame: Week 15 ]
    Relative percent change in liver fat percentage from Baseline to Post-Treatment MRI

  2. Proportion of subjects with ≥ 30% relative reduction in liver fat percentage [ Time Frame: Week 15 ]
    Proportion of subjects with ≥ 30% relative reduction in liver fat percentage from Baseline to Post-Treatment

  3. Percent change in plasma lipoprotein profile [ Time Frame: Week 14 ]
    Percent change in plasma lipoprotein profile (triglycerides, total cholesterol, LDL-C, apolipoprotein B (apoB), very low density lipoproteins (VLDL), HDL, and Non-HDL) 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)

  4. Percent change in parameters of IR [ Time Frame: Week 14 ]
    Percent change in parameters of IR (FPG, insulin, and homeostatic model assessment - insulin resistance (HOMA-IR)) from Baseline to Post-Treatment

  5. Absolute change in HbA1C [ Time Frame: Week 14 ]
    Absolute change in HbA1C from Baseline to Post-Treatment



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • BMI ≥ 27.0 - ≤ 39.0 kg/m².
  • Diagnosis of Type 2 Diabetes Mellitus with an 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 subject 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03334214


Contacts
Contact: Ionis Pharmaceuticals 1-800-679-4747 patients@ionisph.com

Locations
Canada, Nova Scotia
Ionis Investigational Site Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Ionis Investigational Site Recruiting
Chicoutimi, Quebec, Canada, G7H 7K9
Hungary
Ionis Investigational Site Recruiting
Budapest, Hungary, 1036
Ionis Investigational Site Not yet recruiting
Budapest, Hungary, 1083
Ionis Investigational Site Not yet recruiting
Budapest, Hungary, 1088
Ionis Investigational Site Recruiting
Hatvan, Hungary, 3000
Ionis Investigational Site Recruiting
Miskolc, Hungary, 3529
Ionis Investigational Site Recruiting
Szekesfehervar, Hungary, 8000
Poland
Ionis Investigational Site Recruiting
Bydgoszcz, Poland, 85-863
Ionis Investigational Site Recruiting
Bytom, Poland, 41-902
Ionis Investigational Site Not yet recruiting
Chełm, Poland, 22-100
Ionis Investigational Site Recruiting
Katowice, Poland, 40-752
Ionis Investigational Site Recruiting
Kraków, Poland, 31-501
Ionis Investigational Site Not yet recruiting
Kraków, Poland, 31-530
Ionis Investigational Site Recruiting
Mysłowice, Poland, 41-400
Ionis Investigational Site Recruiting
Wierzchosławice, Poland, 33-122
Ionis Investigational Site Recruiting
Wrocław, Poland, 50-127
Ionis Investigational Site Recruiting
Wrocław, Poland, 50-220
Ionis Investigational Site Recruiting
Wrocław, Poland, 50-349
Ionis Investigational Site Recruiting
Łódź, Poland, 93-509
United Kingdom
Ionis Investigational Site Not yet recruiting
Dundee, United Kingdom, DD1 9SY
Ionis Investigational Site Not yet recruiting
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Investigators
Study Director: Sanjay Bhanot Ionis Pharmaceuticals, Inc.

Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03334214     History of Changes
Other Study ID Numbers: 484137-CS2
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ionis Pharmaceuticals, Inc.:
Hepatic Steatosis
IONIS-DGAT2Rx
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Fatty Liver
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases