Trial · NCT03385239
Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)
NCT03385239, Phase 2, Completed, Akcea Therapeutics; results first posted 2023-01-11
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD). Trials, record NCT03385239. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03385239
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)
- NCT number
- NCT03385239
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 114 participants, actual
- Lead sponsor
- Akcea Therapeutics
- Conditions
- Hypertriglyceridemia, Cardiovascular Diseases
- Interventions
- ISIS 678354, Placebo
- First posted
- 2017-12-28
- Last updated
- 2023-01-11
- Results first posted
- 2023-01-11
Source ClinicalTrials.gov
Registered outcomes8
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. |
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to the 13-week post-treatment follow-up period (Up to approximately 15 months) | 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. |
| 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 | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. |
| Secondary | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L]) | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. |
| Secondary | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. |
| Secondary | 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) | |
| Secondary | 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) | |
| Secondary | 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) |
Source ClinicalTrials.gov
Outcomes8
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. | percent change | MEAN |
| PRIMARY | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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). | Participants | COUNT_OF_PARTICIPANTS |
| 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 | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | 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. | percent change | MEAN |
| SECONDARY | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 150 mg/dL (<= 1.7 Millimoles Per Liter [mmol/L]) | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). | percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants Who Achieved Fasting Triglycerides (TG) <= 100 mg/dL (<= 1.13 mmol/L) | Baseline and Month 6 (Week 25 for Cohorts A and B and Week 27 for Cohorts C and D) | FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 678354 or placebo). | percentage of participants | NUMBER |
| SECONDARY | 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) | 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. | nanograms per milliliter (ng/mL) | GEOMETRIC_MEAN |
| SECONDARY | 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) | 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. | hours (h) | MEDIAN |
| SECONDARY | 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) | 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. | nanograms*hours per milliliter (ng*h/mL) | GEOMETRIC_MEAN |
Source ClinicalTrials.gov
Results by group84
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Pooled Placebo | 6 | 95% Confidence Interval -9 to 23 | percent change | |
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Cohort A: ISIS 678354: 10 mg Q4W | -23 | 95% Confidence Interval -34 to -10 | percent change | |
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Cohort C: ISIS 678354: 15 mg Q2W | -56 | 95% Confidence Interval -62 to -49 | percent change | |
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Cohort D: ISIS 678354: 10 mg QW | -60 | 95% Confidence Interval -66 to -54 | percent change | |
| Percent Change From Baseline in Fasting Triglycerides (TG) at the Primary Analysis Time Point | Cohort B: ISIS 678354: 50 mg Q4W | -60 | 95% Confidence Interval -65 to -53 | percent change | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Pooled Placebo | 20 | Participants | ||
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Cohort A: ISIS 678354: 10 mg Q4W | 17 | Participants | ||
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Cohort C: ISIS 678354: 15 mg Q2W | 20 | Participants | ||
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Cohort D: ISIS 678354: 10 mg QW | 22 | Participants | ||
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Cohort B: ISIS 678354: 50 mg Q4W | 21 | Participants |
1 to 10 of 84Source ClinicalTrials.gov
See all 84 results by groupParticipant flow15
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Pooled Placebo | 24 | |
| Overall Study | STARTED | Cohort A: ISIS 678354: 10 mg Q4W | 22 | |
| Overall Study | STARTED | Cohort C: ISIS 678354: 15 mg Q2W | 23 | |
| Overall Study | STARTED | Cohort D: ISIS 678354: 10 mg QW | 23 | |
| Overall Study | STARTED | Cohort B: ISIS 678354: 50 mg Q4W | 22 | |
| Overall Study | COMPLETED | Pooled Placebo | 22 | |
| Overall Study | COMPLETED | Cohort A: ISIS 678354: 10 mg Q4W | 19 | |
| Overall Study | COMPLETED | Cohort C: ISIS 678354: 15 mg Q2W | 20 | |
| Overall Study | COMPLETED | Cohort D: ISIS 678354: 10 mg QW | 19 | |
| Overall Study | COMPLETED | Cohort B: ISIS 678354: 50 mg Q4W | 22 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 participant flowAdverse events290
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Nasopharyngitis | Infections and infestations | Pooled Placebo | 3 | 24 | |
| other | Nasopharyngitis | Infections and infestations | Cohort A: ISIS 678354: 10 mg Q4W | 3 | 22 | |
| other | Nasopharyngitis | Infections and infestations | Cohort C: ISIS 678354: 15 mg Q2W | 4 | 23 | |
| other | Nasopharyngitis | Infections and infestations | Cohort D: ISIS 678354: 10 mg QW | 5 | 23 | |
| other | Nasopharyngitis | Infections and infestations | Cohort B: ISIS 678354: 50 mg Q4W | 4 | 22 | |
| other | Upper respiratory tract infection | Infections and infestations | Pooled Placebo | 3 | 24 | |
| other | Upper respiratory tract infection | Infections and infestations | Cohort A: ISIS 678354: 10 mg Q4W | 2 | 22 | |
| other | Upper respiratory tract infection | Infections and infestations | Cohort C: ISIS 678354: 15 mg Q2W | 3 | 23 | |
| other | Upper respiratory tract infection | Infections and infestations | Cohort D: ISIS 678354: 10 mg QW | 4 | 23 | |
| other | Upper respiratory tract infection | Infections and infestations | Cohort B: ISIS 678354: 50 mg Q4W | 3 | 22 |
1 to 10 of 290Source ClinicalTrials.gov
See all 290 adverse eventsAdverse event totals15
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Pooled Placebo | 0 | 24 |
| Total, all-cause mortality | Cohort A: ISIS 678354: 10 mg Q4W | 0 | 22 |
| Total, all-cause mortality | Cohort C: ISIS 678354: 15 mg Q2W | 1 | 23 |
| Total, all-cause mortality | Cohort D: ISIS 678354: 10 mg QW | 0 | 23 |
| Total, all-cause mortality | Cohort B: ISIS 678354: 50 mg Q4W | 0 | 22 |
| Total, other adverse events | Pooled Placebo | 16 | 24 |
| Total, other adverse events | Cohort A: ISIS 678354: 10 mg Q4W | 15 | 22 |
| Total, other adverse events | Cohort C: ISIS 678354: 15 mg Q2W | 19 | 23 |
| Total, other adverse events | Cohort D: ISIS 678354: 10 mg QW | 20 | 23 |
| Total, other adverse events | Cohort B: ISIS 678354: 50 mg Q4W | 22 | 22 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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