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| Name | Class |
|---|---|
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
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This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 678354 and to assess the efficacy of different doses and dosing regimens of ISIS 678354 for reduction of serum triglyceride (TG) levels in participants with hypertriglyceridemia and established CVD or at a high risk for CVD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pooled Placebo | Placebo Comparator | Participants in each cohort (A, B, C and D) were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354). |
|
| Cohort A: ISIS 678354: 10 mg Q4W | Experimental | Cohort A participants received 10 milligrams (mg) ISIS 678354, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses. |
|
| Cohort C: ISIS 678354: 15 mg Q2W | Experimental | Cohort C participants received 15 mg ISIS 678354, SC injection, once every 2 weeks (Q2W) for up to 51 weeks and a maximum of 26 doses. |
|
| Cohort D: ISIS 678354: 10 mg QW | Experimental | Cohort D participants received 10 mg ISIS 678354, SC injection, once weekly (QW) for up to 52 weeks and a maximum of 52 doses. |
|
| Cohort B: ISIS 678354: 50 mg Q4W | Placebo Comparator | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ISIS 678354 | Drug | ISIS 678354 solution for SC injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | An analysis of covariance (ANCOVA) model was performed on the log ratio of TG value at the Primary Analysis Time Point to TG value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: (ratio of TG value at the Primary Analysis Time Point to TG value at Baseline - 1) × 100. | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (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 to be related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug. | Up to the 13-week post-treatment follow-up period (Up to approximately 15 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I at the Primary Analysis Time Point | An ANCOVA model was performed on the log ratio of Primary Analysis Time Point value to Baseline value for ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I. The estimate of the log ratio was converted back to the original scale and percent change for each lipid parameter was calculated using formula: (ratio of Primary Analysis Time Point value to Baseline value - 1) × 100. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/transient ischemic attack (TIA).
Within 3 months of Screening: coronary, carotid, or peripheral arterial revascularization, major non-cardiac surgery, or lipoprotein apheresis.
Heart failure New York Heart Association (NYHA) class IV.
Type 1 diabetes mellitus.
Type 2 diabetes mellitus with any of the following:
Body Mass Index (BMI) greater than (>) 40 kilograms per square meter (kg/m^2).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Site | Cottonwood | Arizona | 86326 | United States | ||
| Clinical Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35025993 | Derived | Tardif JC, Karwatowska-Prokopczuk E, Amour ES, Ballantyne CM, Shapiro MD, Moriarty PM, Baum SJ, Hurh E, Bartlett VJ, Kingsbury J, Figueroa AL, Alexander VJ, Tami J, Witztum JL, Geary RS, O'Dea LSL, Tsimikas S, Gaudet D. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022 Apr 6;43(14):1401-1412. doi: 10.1093/eurheartj/ehab820. |
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114 participants were randomized in a 1:1:1:1 ratio to Cohorts A, B, C or D. In each cohort, participants were randomized in a 4:1 ratio to receive ISIS 678354 or placebo. Placebo participants from all cohorts were pooled for analysis and presented as the pooled placebo group.
Participants with a clinical diagnosis of hypertriglyceridemia and established cardiovascular disease (CVD) or at high risk for CVD were enrolled in 32 study sites in United States and Canada between 30 January 2018 to 25 February 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pooled Placebo | Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354). |
| FG001 | Cohort A: ISIS 678354: 10 mg Q4W | Cohort A participants received 10 milligrams (mg) ISIS 678354, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses. |
| 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 | Dec 17, 2019 |
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|
| Placebo | Drug | Sterile Normal Saline (0.9% NaCl). |
|
| Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
| Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L]) | The percentage of participants who achieved <= 150 mg/dL or <= 1.7 mmol/L of fasting TG levels at the primary analysis time point were compared between each ISIS 678354 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline TG value as a covariate. | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
| Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) | The percentage of participants who achieved <= 100 mg/dL or <= 1.13 mmol/L of fasting TG levels at the primary analysis time point were compared between each ISIS 678354 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline TG value as a covariate. | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
| Maximum Plasma Concentration (Cmax) of ISIS 678354 | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
| Time to Reach Maximum Plasma Concentration (Tmax) of ISIS 678354 | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of ISIS 678354 | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Clinical Site | Carmichael | California | 95608 | United States |
| Clinical Site | Fresno | California | 93720 | United States |
| Clinical Site | La Jolla | California | 92037-7410 | United States |
| Clinical Site | Long Beach | California | 90807 | United States |
| Clinical Site | Montclair | California | 91763 | United States |
| Clinical Site | Wilmington | Delaware | 19803 | United States |
| Clinical Site | Boca Raton | Florida | 33434 | United States |
| Clinical Site | Jacksonville | Florida | 32216 | United States |
| Clinical Site | New Port Richey | Florida | 34652 | United States |
| Clinical Site | Munster | Indiana | 46321 | United States |
| Clinical Site | Ames | Iowa | 50010 | United States |
| Clinical Site | Kansas City | Kansas | 66160 | United States |
| Clinical Site | Louisville | Kentucky | 40213 | United States |
| Clinical Site | Fall River | Massachusetts | 02721 | United States |
| Clinical Site | Cooperstown | New York | 13326 | United States |
| Clinical Site | High Point | North Carolina | 27262 | United States |
| Clinical Site | Portland | Oregon | 97239 | United States |
| Clinical Site | Lansdale | Pennsylvania | 19446 | United States |
| Clinical Site | Providence | Rhode Island | 02906 | United States |
| Clinical Site | Greer | South Carolina | 29651 | United States |
| Clinical Site | Houston | Texas | 77030 | United States |
| Clinical Site | Milwaukee | Wisconsin | 53215 | United States |
| Clinical Site | Cambridge | Ontario | N1R 6V6 | Canada |
| Clinical Site | Greater Sudbury | Ontario | P3E 5M4 | Canada |
| Clinical Site | Brossard | Quebec | J4Z 2K9 | Canada |
| Clinical Site | Chicoutimi | Quebec | Canada |
| Clinical Site | Gatineau | Quebec | J8Y 6S8 | Canada |
| Clinical Site | Montreal | Quebec | H1T 1C8 | Canada |
| Clinical Site | Québec | Quebec | G1V 4W2 | Canada |
| FG002 | Cohort C: ISIS 678354: 15 mg Q2W | Cohort C participants received 15 mg ISIS 678354, SC injection, once every 2 weeks (Q2W) for up to 51 weeks and a maximum of 26 doses. |
| FG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, once weekly (QW) for up to 52 weeks and a maximum of 52 doses. |
| FG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
| COMPLETED | Completed here refers to participants who completed post-treatment follow-up. |
|
| NOT COMPLETED |
|
|
Full analysis set (FAS) included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo).
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| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Placebo | Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354). |
| BG001 | Cohort A: ISIS 678354: 10 mg Q4W | Cohort A participants received 10 mg ISIS 678354, SC injection, Q4W, for up to 49 weeks and a maximum of 13 doses. |
| BG002 | Cohort C: ISIS 678354: 15 mg Q2W | Cohort C participants received 15 mg ISIS 678354, SC injection, Q2W for up to 51 weeks and a maximum of 26 doses. |
| BG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. |
| BG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Fasting Triglycerides (TG) | Mean | Standard Deviation | milligrams per deciliter (mg/dL) |
| |||||||||||||||
| Apolipoprotein CIII (ApoC-III) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Total Cholesterol (TC) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| LDL Cholesterol (LDL-C) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| HDL Cholesterol (HDL-C) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Non-HDL Cholesterol (Non-HDL-C) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| VLDL Cholesterol (VLDL-C) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Apolipoprotein B (ApoB) | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Apolipoprotein A1 (ApoA-I) | Mean | Standard Deviation | mg/dL |
|
| 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 | Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | An analysis of covariance (ANCOVA) model was performed on the log ratio of TG value at the Primary Analysis Time Point to TG value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: (ratio of TG value at the Primary Analysis Time Point to TG value at Baseline - 1) × 100. | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). Here, 'Number analyzed' ('n') = Participants evaluable for this outcome measure at the specified timepoint. | Posted | Mean | 95% Confidence Interval | percent change | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (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 to be related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug. | Safety set included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). | Posted | Count of Participants | Participants | Up to the 13-week post-treatment follow-up period (Up to approximately 15 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I at the Primary Analysis Time Point | An ANCOVA model was performed on the log ratio of Primary Analysis Time Point value to Baseline value for ApoC-III, TC, LDL-C, HDL-C, Non-HDL-C, VLDL-C, ApoB, and ApoA-I. The estimate of the log ratio was converted back to the original scale and percent change for each lipid parameter was calculated using formula: (ratio of Primary Analysis Time Point value to Baseline value - 1) × 100. | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). Here, 'Number analyzed' ('n') = Participants evaluable for this outcome measure for each specified category. | Posted | Mean | 95% Confidence Interval | percent change | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
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| Secondary | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L]) | The percentage of participants who achieved <= 150 mg/dL or <= 1.7 mmol/L of fasting TG levels at the primary analysis time point were compared between each ISIS 678354 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline TG value as a covariate. | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). | Posted | Number | percentage of participants | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) | The percentage of participants who achieved <= 100 mg/dL or <= 1.13 mmol/L of fasting TG levels at the primary analysis time point were compared between each ISIS 678354 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline TG value as a covariate. | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). | Posted | Number | percentage of participants | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) |
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| Secondary | Maximum Plasma Concentration (Cmax) of ISIS 678354 | Pharmacokinetic (PK) subgroup: Subset of participants who were randomized, received at least (>=) 1 dose of ISIS 678354, had >= 1 evaluable concentration result post first dose and had additional PK sampling after dose administration on Day 1 and Week 21 (Cohorts A and B) or Week 25 (Cohorts C and D). 'Number analyzed' = participants evaluable for this outcome measure at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of ISIS 678354 | PK subgroup: Subset of participants who were randomized, received >= 1 dose of ISIS 678354, had >= 1 evaluable concentration result post first dose and had additional PK sampling after dose administration on Day 1 and Week 21 (Cohorts A and B) or Week 25 (Cohorts C and D). 'Number analyzed' = participants evaluable for this outcome measure at specified time points. | Posted | Median | Full Range | hours (h) | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
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| Secondary | Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of ISIS 678354 | PK subgroup: Subset of participants who were randomized, received >= 1 dose of ISIS 678354, had >= 1 evaluable concentration result post first dose and had additional PK sampling after dose administration on Day 1 and Week 21 (Cohorts A and B) or Week 25 (Cohorts C and D). 'Number analyzed' = participants evaluable for this outcome measure at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Predose, 1, 2, 4, 8, 24 hours post the first dose (Day 1), Week 21 (for Cohorts A and B) and Week 25 (for Cohorts C and D) |
|
Up to the 13-week post-treatment follow-up period (Up to approximately 15 months)
Safety set included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pooled Placebo | Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354). | 0 | 24 | 2 | 24 | 16 | 24 |
| EG001 | Cohort A: ISIS 678354: 10 mg Q4W | Cohort A participants received 10 mg ISIS 678354, SC injection, Q4W, for up to 49 weeks and a maximum of 13 doses. | 0 | 22 | 3 | 22 | 15 | 22 |
| EG002 | Cohort C: ISIS 678354: 15 mg Q2W | Cohort C participants received 15 mg ISIS 678354, SC injection, Q2W for up to 51 weeks and a maximum of 26 doses. | 1 | 23 | 4 | 23 | 19 | 23 |
| EG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. | 0 | 23 | 1 | 23 | 20 | 23 |
| EG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. | 0 | 22 | 3 | 22 | 22 | 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Post polio syndrome | Nervous system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Henoch-Schonlein purpura | Skin and subcutaneous tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Injection site haemorrhage | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Glomerular filtration rate decreased | Investigations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Prostatic specific antigen increased | Investigations | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA Version 20.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 20.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 20.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA Version 20.1 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Akcea Therapeutics | 617-207-0289 | clinicalstudies@akceatx.com |
| Dec 19, 2022 |
| Prot_SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015228 | Hypertriglyceridemia |
| D002318 | Cardiovascular Diseases |
| D050171 | Dyslipidemias |
| D008659 | Metabolic Diseases |
| D006949 | Hyperlipidemias |
| D006331 | Heart Diseases |
| D052439 | Lipid Metabolism Disorders |
| D014652 | Vascular Diseases |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| ANCOVA |
| <0.0001 |
| Mean Difference in % CFB |
| -58 |
| 2-Sided |
| 95 |
| -66 |
| -48 |
Mean difference in % CFB based on difference in LSM of log (Primary Analysis Time Point/Baseline) was estimated. |
| Superiority |
| ANCOVA | <0.0001 | Mean Difference in % CFB | -63 | 2-Sided | 95 | -70 | -54 | Mean difference in % CFB based on difference in LSM of log (Primary Analysis Time Point/Baseline) was estimated. | Superiority |
| ANCOVA | <0.0001 | Mean Difference in % CFB | -62 | 2-Sided | 95 | -69 | -53 | Mean difference in % CFB based on difference in LSM of log (Primary Analysis Time Point/Baseline) was estimated. | Superiority |
| OG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. |
| OG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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Cohort C participants received 15 mg ISIS 678354, SC injection, Q2W for up to 51 weeks and a maximum of 26 doses.
| OG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. |
| OG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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| OG003 | Cohort D: ISIS 678354: 10 mg QW | Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. |
| OG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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| OG003 |
| Cohort D: ISIS 678354: 10 mg QW |
Cohort D participants received 10 mg ISIS 678354, SC injection, QW for up to 52 weeks and a maximum of 52 doses. |
| OG004 | Cohort B: ISIS 678354: 50 mg Q4W | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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| Cohort B: ISIS 678354: 50 mg Q4W |
Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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| OG003 |
| Cohort B: ISIS 678354: 50 mg Q4W |
Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
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