Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03070782 | Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease | PHASE2 | COMPLETED | 286 | — | — | Mar 7, 2017 | Nov 13, 2018 | Oct 30, 2020 | 32 | United States, Canada +3 |
| NCT03392051 | Drug-drug Interaction Study to Evaluate the Effect of ISIS 681257 on Clopidogrel | PHASE1 | COMPLETED | 18 | — | — | Dec 28, 2017 | Mar 18, 2018 | Apr 5, 2018 | 1 | Canada |
| NCT03426033 | Drug-drug Interaction Study to Evaluate the Effect of ISIS 681257 on Warfarin | PHASE1 | COMPLETED | 18 | — | — | Dec 15, 2017 | Feb 25, 2018 | Apr 5, 2018 | 1 | Canada |
An ANCOVA model was performed on the log ratio of Lp(a) value at the Primary Analysis Time Point to Lp(a) 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 Lp(a) value at the Primary Analysis Time Point to Lp(a) value at Baseline - 1) × 100.
An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), 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 was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study.
An AE was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), 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 was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. The severity of TEAEs was assessed based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.
An AE was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), 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. TEAE was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study.
The plasma concentrations of Clopidogrel and ISIS 681257 will be measured at each individual time point.
To evaluate the effect of multiple doses of ISIS 681257 40 mg subcutaneous injections on the pharmacokinetics of a single oral dose of warfarin in healthy adult subjects.
| Arm | Type | Description |
|---|---|---|
| Cohort A: ISIS 681257: 20 mg Q4W | EXPERIMENTAL | Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses. |
| Cohort B: ISIS 681257: 40 mg Q4W | EXPERIMENTAL | Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses. |
| Cohort C: ISIS 681257: 60 mg Q4W | EXPERIMENTAL | Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses. |
| Cohort D: ISIS 681257: 20 mg Q2W | EXPERIMENTAL | Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses. |
| Cohort E: ISIS 681257: 20 mg QW | EXPERIMENTAL | Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses. |
| Placebo | PLACEBO_COMPARATOR | Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257). |
| Clopidogrel Dosing | EXPERIMENTAL | Multiple doses of Clopidogrel to obtain pharmacokinetic information. |
| Clopidogrel in combination with ISIS 681257 | EXPERIMENTAL | Multiple doses of clopidogrel administered with 2 doses of ISIS 681257 at 2 individual timepoints to obtain pharmacokinetic information. |
| Single dose of warfarin | EXPERIMENTAL | Single dose of warfarin administered to obtain pharmacokinetic information. |
| Warfarin in combination with ISIS 681257 | EXPERIMENTAL | ISIS 681257 administered and pharmacokinetic assessments are taken. Then ISIS 681257 is administered with warfarin and additional pharmacokinetic information is obtained. |
| Name | Type | Description |
|---|---|---|
| ISIS 681257 | DRUG | ISIS 681257 solution for SC injection. |
| Placebo | DRUG | Sterile normal saline (0.9% NaCl) |
| Clopidogrel | DRUG | 75mg tablet administered orally |
| Warfarin | DRUG | 25mg tablet administered orally |
Key Inclusion Criteria: * Clinical diagnosis of CVD defined as documented coronary artery disease, stroke, or peripheral artery disease * Lp(a) plasma level ≥ 60 mg/dL * Must be on standard-of-care preventative therapy for other than elevated Lp(a) CVD risk factors Key Exclusion Criteria: * Withi...