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NAFLDPhase 2NCT03371355

Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

A Phase 2 study testing ISIS 703802 40 mg, ISIS 703802 80 mg and ISIS 703802 20 mg in people with NAFLD and Diabetes Mellitus, Type 2, run by Akcea Therapeutics at 42 sites in 2 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

This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 703802 and to assess the efficacy of different doses and dosing regimens of ISIS 703802 on glucose and lipid metabolism, and liver fat in participants with… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
ISIS 703802 40 mg, ISIS 703802 80 mg and ISIS 703802 20 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
105 participants
Where
42 sitesin 2 countries
Study dates
21 Dec 2017to 24 Feb 2020
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Plasma triglycerides (TG) at Screening greater than (>)150 milligrams per deciliter (mg/dL) and at qualification of >150 mg/dL.
  • Documented history of hepatic steatosis with baseline magnetic resonance imaging (MRI) indicating hepatic fat fraction (HFF) greater than (>) 8%.
  • Diagnosis of Type 2 diabetes mellitus with hemoglobin A1c (HbA1c) >6.5 and less than or equal to (≤) 10% at Screening.
  • Must have been on a stable dose of oral antidiabetic therapy for a minimum of 3 months prior to Screening.
  • Body mass index between 27- 40 kilograms per meter square (kg/m^2), inclusive, at Screening.

Who cannot join

  • Type 1 diabetes mellitus.
  • Active chronic liver disease, alcoholic liver disease, Wilson's disease hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, known or suspected hepatocellular carcinoma, history of or planned liver transplant for end-stage liver disease of any etiology.
  • Documented history of advanced liver fibrosis.
  • History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy, or variceal bleeding.
  • History of clinically significant acute cardiac event within 6 months before Screening.
  • History of heart failure with New York Heart Association (NYHA) greater than Class II.
Show all 9Show fewer
  • Use of Insulin or insulin analogs, glucagon-like peptide-1 (GLP-1) agonists, and peroxisome proliferator-activated receptor gamma (PPARᵞ) agonists (pioglitazone or rosiglitazone).
  • Weight change >5% within 3 months before Screening.
  • Conditions contraindicated for magnetic resonance imaging (MRI) procedures including any metal implant (example, heart pacemaker, rods, screws, aneurysm clips).

Trial locations and contacts

42 sites in 2 countries.

42 sites in 2 countries

United States38 sites

  • Clinical Site

    Atlanta, Georgia, 30328

  • Clinical Site

    Austin, Texas, 78735

  • Clinical Site

    Boca Raton, Florida, 33487

  • Clinical Site

    Bridgeton, New Jersey, 08302

  • Clinical Site

    Carrollton, Texas, 75010

  • Clinical Sites

    Chandler, Arizona, 85224

  • Clinical Site

    Charleston, South Carolina, 29407

  • Clinical Site

    Chicago, Illinois, 60640

  • Clinical Site

    Cincinnati, Ohio, 45219

  • Clinical Site

    Cincinnati, Ohio, 45227

  • Clinical Site

    Dallas, Texas, 75234

  • Clinical Site

    Edina, Minnesota, 55435

  • Clinical Site

    Fountain Hills, Arizona, 85268

  • Clinical Site

    Glendale, Arizona, 85306

  • Clinical Site

    Greensboro, North Carolina, 27410

  • Clinical Site

    High Point, North Carolina, 27265

  • Clinical Site

    Houston, Texas, 77058

  • Clinical Site

    Huntington Park, California, 90255

  • Clinical Site

    Hurst, Texas, 76054

  • Clinical Site

    Indianapolis, Indiana, 46260

  • Clinical Site

    Jensen Beach, Florida, 34957

  • Clinical Site

    Jupiter, Florida, 33458

  • Clinical Site

    Layton, Utah, 84041

  • Clinical Site

    Los Angeles, California, 90057

  • Clinical Site

    Louisville, Kentucky, 40213

  • Clinical Site

    Mesa, Arizona, 85206

  • Clinical Site

    Mesa, Arizona, 85213

  • Clinical Site

    Miami, Florida, 33165

  • Clinical Site

    Montclair, California, 91710

  • Clinical Site

    Panorama City, California, 91402

  • Clinical Site

    Phoenix, Arizona, 85020

  • Clinical Site

    Phoenix, Arizona, 85023

  • Clinical Site

    Phoenix, Arizona, 85050

  • Clinical Site

    Port Saint Lucie, Florida, 34952

  • Clinical Site

    Poway, California, 92064

  • Clinical Site

    Princeton, New Jersey, 08540

  • Clinical Site

    San Antonio, Texas, 78215

  • Clinical Site

    San Antonio, Texas, 78229

Other trials in United States

Canada4 sites

  • Clinical Site

    Chicoutimi, Quebec, G7H 7K9

  • Clinical Site

    Hamilton, Ontario, L8L 5G8

  • Clinical Site

    Montreal, Quebec, H4A 2C6

  • Clinical Site

    Toronto, Ontario, M3M 3E5

Other trials in Canada

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Finding Study of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus (T2DM), and Nonalcoholic Fatty Liver Disease (NAFLD)

This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 703802 and to assess the efficacy of different doses and dosing regimens of ISIS 703802 on glucose and lipid metabolism, and liver fat in participants with hypertriglyceridemia, Type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD).

Being tested
Placebo, ISIS 703802 40 mg, ISIS 703802 80 mg, ISIS 703802 20 mg
Keywords
Type 2 Diabetes, Hepatic Steatosis, Triglycerides, AKCEA-ANGPTL3-Lrx, IONIS-ANGPTL3-Lrx, Fatty Liver, Fatty Liver Without Mention of Alcohol, Liver Fat, Liver Diseases, Diabetes Mellitus Type 2 in Nonobese, Diabetes Mellitus, Triglycerides High, High Triglycerides, Metabolic Disease, Endocrine System Diseases, Digestive System Disease, Glucose Metabolism Disorders, Vupanorsen
Medical subject headings
Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Hypertriglyceridemia, Fatty Liver, Liver Diseases, Diabetes Mellitus, Metabolic Diseases, Endocrine System Diseases

What participants receive

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

  • PlaceboDrug

    Also called Sterile Normal Saline (0.9% NaCl)

    Placebo (Matched with ISIS 703802)

  • ISIS 703802 40 mgDrug

    Also called AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx, Vupanorsen

    ISIS 703802 40 mg, administered via SC injection, once every 4 weeks for 6 doses.

  • ISIS 703802 80 mgDrug

    Also called AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx, Vupanorsen

    ISIS 703802 80 mg, administered via SC injection, once every 4 weeks for 6 doses.

  • ISIS 703802 20 mgDrug

    Also called AKCEA-ANGPTL3-LRx, IONIS-ANGPTL3-LRx, Vupanorsen

    ISIS 703802 20 mg, administered via SC injection, once every week for 26 doses.

Study groups in NCT03371355
Study groupRoleWhat they receive
Pooled PlaceboPlacebo comparatorParticipants from each cohort received placebo at a dose-matched volume of study drug, subcutaneously (SC).
Receives: Drug: Placebo
Cohort B: ISIS 703802, 40 mg Q4WExperimentalParticipants received ISIS 703802, 40 milligrams (mg) SC once every 4 weeks for 6 doses.
Receives: Drug: ISIS 703802 40 mg
Cohort C: ISIS 703802, 80 mg Q4WExperimentalParticipants received ISIS 703802, 80 mg SC once every 4 weeks for 6 doses.
Receives: Drug: ISIS 703802 80 mg
Cohort A: ISIS 703802, 20 mg QWExperimentalParticipants received ISIS 703802, 20 mg once every week for 26 doses.
Receives: Drug: ISIS 703802 20 mg

What is being measured

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

  1. Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point

    An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Secondary outcomes (26)

  1. Change From Baseline in Angiopoietin-Like 3 Protein at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  2. Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  3. Change From Baseline in Free Fatty Acid (FFA) at Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  4. Change From Baseline in Lipoprotein(a) (Lp[a]) at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  5. Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point

    An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  6. Change From Baseline in Fasting Plasma Glucose at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  7. Change From Baseline in Hemoglobin A1c (HbA1c) at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  8. Change From Baseline in Fasting Insulin at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  9. Change From Baseline in and HOMA-IR at the Primary Analysis Time Point

    HOMA-IR is a method used to quantify insulin resistance. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/mL) * fasting plasma glucose (mmol/L)/22.5. A negative change from Baseline indicates improvement. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  10. Change From Baseline in Fructosamine at Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  11. Change From Baseline in Glycated Albumin at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  12. Change From Baseline in Weight at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  13. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  14. Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point

    An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C6

  15. Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  16. Percent Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point

    An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  17. Percentage of Participants With HFF ≤ 8% by MRI-PDFF at the Primary Analysis Time Point

    The percentage of participants who achieved HFF ≤ 8% at the Primary Analysis Time Point was compared between each ISIS 703802 treatment group and pooled placebo group using a logistic regression model.

    Measured: Week 27 for Cohort A, and Week 25 for Cohorts B and C

  18. Change From Baseline in Fatty Liver Index (FLI) at the Primary Analysis Time Point

    The FLI was calculated by the following formula: FLI =(e0.953×loge[triglycerides]+0.139× Body Mass Index [BMI]+0.718×loge Gamma- Glutamyl Transferase [GGT]+0.053×waistcircumference-15.745)/ (1 + e0.953×loge[triglycerides]+0.139×BMI+0.718×loge [GGT]+0.053×waistcircumference-15.745) × 100. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  19. Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  20. Change From Baseline in Leptin at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  21. Change From Baseline in Adiponectin at the Primary Analysis Time Point

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  22. Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  23. Change From Baseline in Waist Circumference by Single Slice MRI at the Primary Analysis Timepoint

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  24. Change From Baseline in Waist to Hip Ratio (WHR) at the Primary Analysis Timepoint

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  25. Change From Baseline in Body Mass Index (BMI) at the Primary Analysis Timepoint

    An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

    Measured: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

  26. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    An AE was defined as 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 was considered related to the investigational drug product. TEAEs were defined as adverse events that occurred after the first administration of study drug.

    Measured: Up to 13 weeks post treatment period (up to 39 weeks)

Timeline

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

  1. First posted13 Dec 2017
  2. Study start21 Dec 2017
  3. Primary completion21 Nov 2019
  4. Study completion24 Feb 2020

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03371355
Sponsor's protocol ID
ISIS 703802-CS2
Status last verified
Dec 2020
First submitted
27 Nov 2017
Last updated
1 Feb 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ISIS 703802 40 mg, ISIS 703802 80 mg and ISIS 703802 20 mg in people with NAFLD and Diabetes Mellitus, Type 2, run by Akcea Therapeutics at 42 sites in 2 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 5 inclusion and 9 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 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States, Canada. 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 1 Feb 2021). 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?

Percent Change From Baseline in Fasting Triglycerides Level at the Primary Analysis Time Point (time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C). 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 NCT03371355.

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 1 Feb 2021; AzTrials last refreshed its copy on 7 Nov 2026.

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