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Hepatic SteatosisPhase 2NCT03334214

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

A Phase 2 study testing IONIS DGAT2Rx in people with Hepatic Steatosis, run by Ionis Pharmaceuticals, Inc. at 22 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatic Steatosis
What is being tested?
IONIS DGAT2Rx
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
44 participants
Where
22 sitesin 4 countries
Study dates
3 Nov 2017to 28 Nov 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

22 sites in 4 countries.

22 sites in 4 countries

Poland12 sites

  • Ionis Investigational Site

    Bydgoszcz, 85-863

  • Ionis Investigational Site

    Bytom, 41-902

  • Ionis Investigational Site

    Chełm, 22-100

  • Ionis Investigational Site

    Katowice, 40-752

  • Ionis Investigational Site

    Krakow, 31-501

  • Ionis Investigational Site

    Krakow, 31-530

  • Ionis Investigational Site

    Lodz, 93-509

  • Ionis Investigational Site

    Mysłowice, 41-400

  • Ionis Investigational Site

    Wierzchosławice, 33-122

  • Ionis Investigational Site

    Wroclaw, 50-127

  • Ionis Investigational Site

    Wroclaw, 50-220

  • Ionis Investigational Site

    Wroclaw, 50-349

Other trials in Poland

Hungary6 sites

  • Ionis Investigational Site

    Budapest, 1036

  • Ionis Investigational Site

    Budapest, 1083

  • Ionis Investigational Site

    Budapest, 1088

  • Ionis Investigational Site

    Hatvan, 3000

  • Ionis Investigational Site

    Miskolc, 3529

  • Ionis Investigational Site

    Székesfehérvár, 8000

Other trials in Hungary

Canada2 sites

  • Ionis Investigational Site

    Chicoutimi, Quebec, G7H 7K9

  • Ionis Investigational Site

    Halifax, Nova Scotia, B3H 2Y9

Other trials in Canada

United Kingdom2 sites

  • Ionis Investigational Site

    Dundee, DD1 9SY

  • Ionis Investigational Site

    Nottingham, NG7 2UH

Other trials in United Kingdom

About this study

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

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

Read the 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.

Being tested
IONIS DGAT2Rx, Placebo
Keywords
Hepatic Steatosis, IONIS-DGAT2Rx, Type 2 Diabetes
Medical subject headings
Fatty Liver, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IONIS DGAT2RxDrug

    Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks

  • PlaceboDrug

    Saline 0.9%

Study groups in NCT03334214
Study groupRoleWhat they receive
IONIS DGAT2RxExperimentalSingle Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks
Receives: Drug: IONIS DGAT2Rx
Placebo (sterile saline 0.9)Placebo comparatorCalculated volume to match active comparator administered subcutaneously once weekly for 13 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to Week 15

  2. 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.

    Measured: Baseline to Week 15

  3. 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.

    Measured: Up to 176 days

  4. 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.

    Measured: Up to 176 days

Secondary outcomes (6)

  1. Percent Change in Liver Fat Percentage

    Relative percent change in liver fat percentage from baseline to post-treatment MRI.

    Measured: Baseline to Week 15

  2. 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.

    Measured: Week 15

  3. Percent Change in Liver Volume

    Assessed from Baseline MRI to Post-Treatment MRI.

    Measured: Baseline to Week 15

  4. 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).

    Measured: Week 15

  5. 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.

    Measured: Week 14

  6. Absolute Change in Hemoglobin A1C (HbA1C)

    Absolute change in HbA1C from baseline to post-treatment.

    Measured: Week 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2017
  2. Study start3 Nov 2017
  3. Primary completion28 Nov 2018
  4. Study completion28 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03334214
Sponsor's protocol ID
ISIS 484137-CS2
Other IDs
2017-003197-13, 2017
Status last verified
Jan 2020
First submitted
23 Oct 2017
Last updated
27 Jan 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32553151

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IONIS DGAT2Rx in people with Hepatic Steatosis, run by Ionis Pharmaceuticals, Inc. at 22 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Poland, Hungary, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change in Liver Fat Percentage (Randomized Population) (time frame: Baseline to Week 15). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03334214, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.

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