Phase 2
Completed N=44
Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes
Source: ClinicalTrials.gov NCT03334214 ↗Enrolled (actual)
44
Serious AEs
9.1%
Results posted
Jan 2020
Primary outcomePrimary: Absolute Change in Liver Fat Percentage (Randomized Population) — -0.04; -5.37 liver fat percentage — p=0.003
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Change in Liver Fat Percentage (Randomized Population) |
-0.04; -5.37 | 0.003 sig |
| PRIMARY Absolute Change in Liver Fat Percentage (Per Protocol Population) |
-0.64; -5.15 | 0.026 sig |
| PRIMARY Percentage of Participants With Adverse Events That Were Related to Treatment With IONIS DGAT2Rx |
13.3; 48.3 | — |
| PRIMARY Percentage of Participants With Adverse Events, Graded by Severity, That Were Related to Treatment With IONIS DGAT2Rx |
6.7; 37.9; 6.7; 6.9; 0.0; 3.4 | — |
| SECONDARY Percent Change in Liver Fat Percentage |
-2.4; -25.5 | 0.024 sig |
| SECONDARY Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage |
16.7; 48.0 | 0.0774 |
| SECONDARY Percent Change in Liver Volume |
-1.9; -6.3 | 0.183 |
| SECONDARY Percent Change in Plasma Lipoprotein Profile |
-4.4; -2.9; -8.1; -6.7; 1.0; 2.2 | 0.682 |
| SECONDARY Percent Change in Parameters of Insulin Resistance (IR) |
-6.3; -6.9; -16.9; 2.6; -10.3; 10.1 | 0.902 |
| SECONDARY Absolute Change in Hemoglobin A1C (HbA1C) |
-0.2; -0.2 | 0.933 |
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
Data sourced from ClinicalTrials.gov (NCT03334214). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.