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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003197-13 | EudraCT Number |
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The purpose is to assess the Safety, Tolerability, and Pharmacodynamics effect of IONIS DGAT2Rx in up to 45 Adult Patients with Type 2 Diabetes.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IONIS DGAT2Rx | Experimental | Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks |
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| Placebo (sterile saline 0.9) | Placebo Comparator | Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IONIS DGAT2Rx | Drug | Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Week 15 |
| 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. | Baseline to Week 15 |
| 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. | Up to 176 days |
| 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. | Up to 176 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Liver Fat Percentage | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sanjay Bhanot | Ionis Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ionis Investigational Site | Halifax | Nova Scotia | B3H 2Y9 | Canada | ||
| Ionis Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32553151 | Derived | 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. |
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A total of 173 participants were screened for the study and 44 participants were randomized and received study drug.
44 participants were randomized at multiple study centers in Canada, Hungary, and Poland.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks. |
| FG001 | IONIS DGAT2Rx 250 mg | Single dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 6, 2018 |
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| Placebo | Drug | Saline 0.9% |
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Percentage of participants with ≥ 30% relative reduction in liver fat percentage from baseline to post-treatment.
| Week 15 |
| Percent Change in Liver Volume | Assessed from Baseline MRI to Post-Treatment MRI. | Baseline to Week 15 |
| 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). | Week 15 |
| 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. | Week 14 |
| Absolute Change in Hemoglobin A1C (HbA1C) | Absolute change in HbA1C from baseline to post-treatment. | Week 14 |
| Chicoutimi |
| Quebec |
| G7H 7K9 |
| Canada |
| Ionis Investigational Site | Budapest | 1036 | Hungary |
| Ionis Investigational Site | Budapest | 1083 | Hungary |
| Ionis Investigational Site | Budapest | 1088 | Hungary |
| Ionis Investigational Site | Hatvan | 3000 | Hungary |
| Ionis Investigational Site | Miskolc | 3529 | Hungary |
| Ionis Investigational Site | Székesfehérvár | 8000 | Hungary |
| Ionis Investigational Site | Bydgoszcz | 85-863 | Poland |
| Ionis Investigational Site | Bytom | 41-902 | Poland |
| Ionis Investigational Site | Chełm | 22-100 | Poland |
| Ionis Investigational Site | Katowice | 40-752 | Poland |
| Ionis Investigational Site | Krakow | 31-501 | Poland |
| Ionis Investigational Site | Krakow | 31-530 | Poland |
| Ionis Investigational Site | Lodz | 93-509 | Poland |
| Ionis Investigational Site | Mysłowice | 41-400 | Poland |
| Ionis Investigational Site | Wierzchosławice | 33-122 | Poland |
| Ionis Investigational Site | Wroclaw | 50-127 | Poland |
| Ionis Investigational Site | Wroclaw | 50-220 | Poland |
| Ionis Investigational Site | Wroclaw | 50-349 | Poland |
| Ionis Investigational Site | Dundee | DD1 9SY | United Kingdom |
| Ionis Investigational Site | Nottingham | NG7 2UH | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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Randomized Population: All subjects who are randomized into the study regardless of whether they received Study Drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks. |
| BG001 | IONIS DGAT2Rx 250 mg | Single dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Liver Fat Percentage (Randomized Population) | Mean | Standard Deviation | fat percentage |
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| Liver Fat Percentage (Per Protocol Population) | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Mean | Standard Deviation | fat percentage |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The randomized population included all participants who are randomized into the study regardless of whether they received the study drug. | Posted | Mean | Standard Deviation | liver fat percentage | Baseline to Week 15 |
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| Primary | 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. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Mean | Standard Deviation | liver fat percentage | Baseline to Week 15 |
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| Primary | 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. | The safety set included all randomized participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Up to 176 days |
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| Primary | 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. | The safety set included all randomized participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Up to 176 days |
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| Secondary | Percent Change in Liver Fat Percentage | Relative percent change in liver fat percentage from baseline to post-treatment MRI. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Mean | Standard Deviation | percent change | Baseline to Week 15 |
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| Secondary | 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. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Number | percentage of participants | Week 15 |
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| Secondary | Percent Change in Liver Volume | Assessed from Baseline MRI to Post-Treatment MRI. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Mean | Standard Deviation | percent change | Baseline to Week 15 |
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| Secondary | 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). | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Mean | Standard Deviation | percent change | Week 15 |
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| Secondary | 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. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. Number analyzed were the participants with analysis values at specified time point. | Posted | Mean | Standard Deviation | percent change | Week 14 |
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| Secondary | Absolute Change in Hemoglobin A1C (HbA1C) | Absolute change in HbA1C from baseline to post-treatment. | The per protocol set included all randomized participants who received at least 10 of the prescribed doses and received the first 4 doses in the first 5 weeks, not missing 3 consecutive weekly doses and having no significant protocol deviations. | Posted | Mean | Standard Deviation | percentage of total hemoglobin | Week 14 |
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Up to 176 days
The safety set included all randomized participants who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks. | 0 | 15 | 0 | 15 | 10 | 15 |
| EG001 | IONIS DGAT2Rx 250 mg | Single dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks. | 0 | 29 | 4 | 29 | 20 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac arrest | Cardiac disorders | MedDRA (21.0) | Systematic Assessment |
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| Pancreatitis acute | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Ischaemic cerebral infarction | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site erythema | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Injection site bruising | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Vulvovaginal mycotic infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Carotid arteriosclerosis | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Carpal tunnel syndrome | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA (21.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ionis Pharmaceuticals, Inc. | Ionis Pharmaceuticals, Inc. | 800-679-4747 | patients@ionisph.com |
| Nov 22, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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