Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease

Akcea Therapeutics

Status and phase: Completed; Phase 2

Conditions: Elevated Lipoprotein(a); Cardiovascular Disease

Treatments: Drug: ISIS 681257; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03070782

2016-003373-18 (EudraCT Number)

ISIS 681257-CS6

Details and patient eligibility

About

This is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 681257 and to assess the efficacy of different doses and dosing regimens of ISIS 681257 for reduction of plasma Lipoprotein(a) [Lp(a)] levels in participants with hyperlipoproteinemia(a) and established cardiovascular disease (CVD).

Enrollment: 286 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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:

• Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or stroke/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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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286 participants in 6 patient groups, including a placebo group

Cohort A: ISIS 681257: 20 mg Q4W

Experimental group

Description:

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.

Treatment:

Drug: ISIS 681257

Cohort B: ISIS 681257: 40 mg Q4W

Experimental group

Description:

Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.

Treatment:

Drug: ISIS 681257

Cohort C: ISIS 681257: 60 mg Q4W

Experimental group

Description:

Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.

Treatment:

Drug: ISIS 681257

Cohort D: ISIS 681257: 20 mg Q2W

Experimental group

Description:

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.

Treatment:

Drug: ISIS 681257

Cohort E: ISIS 681257: 20 mg QW

Experimental group

Description:

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.

Treatment:

Drug: ISIS 681257

Placebo

Placebo Comparator group

Description:

Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).

Treatment:

Drug: Placebo