Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Pelacarsen, AKCEA-APO(a)-LRx, TQJ230
ISIS 681257 · 5 trials · 5 indications
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 ISIS 681257 will be measured.
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). |
| SAD: Placebo | PLACEBO_COMPARATOR | Single dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 20 milligrams (mg) | EXPERIMENTAL | Single dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 40 mg | EXPERIMENTAL | Single dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| SAD: Pelacarsen 80 mg | EXPERIMENTAL | Single dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period. |
| MD: Placebo | PLACEBO_COMPARATOR | Multiple doses of Pelacarsen-matching placebo administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. |
| MD: Pelacarsen 80 mg | EXPERIMENTAL | Multiple doses of Pelacarsen, 80 mg, administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period. |
| Normal Renal Function | EXPERIMENTAL | Subjects with normal renal function will be matched by age (±10 years), weight (± 20%), and gender to the pooled mean values of subjects with the moderate renal impairment. Subjects will receive 1 dose of ISIS 681257. |
| Moderate Renal Impairment | EXPERIMENTAL | Presence of moderate renal impairment (eGFR 30-59 mL/min/1.73m2). Subjects will receive 1 dose of 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) |
| Pelacarsen | DRUG | Pelacarsen administered by SC injection. |
| 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...
ISIS 681257 is an investigational therapy being developed for elevated lipoprotein(a) in patients with cardiovascular disease. It has also been studied in people with renal impairment. It is designed to lower lipoprotein(a) levels, a risk factor for cardiovascular events. The drug is not yet approved and remains in clinical development.
ISIS 681257 is being developed by Ionis Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker IONS. Ionis is the sponsor of the clinical program, including the Phase 2 study in hyperlipoproteinemia(a) and cardiovascular disease.
ISIS 681257 has completed a Phase 2 clinical trial and is currently in Phase 2 development. The Phase 2 study, NCT03070782, evaluated the drug in participants with hyperlipoproteinemia(a) and cardiovascular disease. The program also includes completed Phase 1 trials. The drug is investigational and has not been approved by the FDA.
ISIS 681257 has been evaluated in four completed clinical trials. The Phase 2 trial is NCT03070782, which enrolled 286 participants with hyperlipoproteinemia(a) and cardiovascular disease. Phase 1 trials include NCT03506854 in renal impairment, NCT03426033 evaluating a warfarin interaction, and NCT03392051 evaluating a clopidogrel interaction.
Yes, ISIS 681257 is also known as AKCEA-APO(a)-LRx. The two names refer to the same investigational drug developed by Ionis Pharmaceuticals. The alternative name appears in the title of the Phase 2 trial, NCT03070782, which studied the drug in participants with hyperlipoproteinemia(a) and cardiovascular disease.