Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ISIS 681257 · 4 trials · 4 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). |
| 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) |
| 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 drug being studied for elevated lipoprotein(a) and cardiovascular disease, as well as for renal impairment. It is in Phase 2 clinical development for these conditions, with the primary study focusing on participants with hyperlipoproteinemia(a) and cardiovascular disease.
ISIS 681257 is being developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol IONS. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with elevated lipoprotein(a) and related cardiovascular conditions.
ISIS 681257 is in Phase 2 clinical development. The most advanced trial is a Phase 2 study in participants with hyperlipoproteinemia(a) and cardiovascular disease, which has been completed. Earlier Phase 1 studies have also been completed to evaluate the drug's effects and interactions.
ISIS 681257 has completed three clinical trials. The main Phase 2 study (NCT03070782) enrolled 286 participants with elevated lipoprotein(a) and cardiovascular disease. Two Phase 1 drug-drug interaction studies evaluated effects on clopidogrel (NCT03392051) and warfarin (NCT03426033), plus a renal impairment study (NCT03506854).
Yes, ISIS 681257 is also known as AKCEA-APO(a)-LRx. The Phase 2 clinical trial NCT03070782 is titled 'Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease,' confirming that both names refer to the same investigational drug.
ISIS 681257 is not FDA approved. It is an investigational drug currently in clinical development, with completed Phase 1 and Phase 2 trials. The drug has not yet received regulatory approval for any indication, and its safety and efficacy continue to be evaluated in clinical studies.