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

NCT ID: NCT03070782

Last Updated: 2020-10-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

286 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-07

Study Completion Date

2018-11-13

Brief Summary

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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).

Detailed Description

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Conditions

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Elevated Lipoprotein(a) Cardiovascular Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Cohort A: ISIS 681257: 20 mg Q4W

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.

Group Type EXPERIMENTAL

ISIS 681257

Intervention Type DRUG

ISIS 681257 solution for SC injection.

Cohort B: ISIS 681257: 40 mg Q4W

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

Group Type EXPERIMENTAL

ISIS 681257

Intervention Type DRUG

ISIS 681257 solution for SC injection.

Cohort C: ISIS 681257: 60 mg Q4W

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

Group Type EXPERIMENTAL

ISIS 681257

Intervention Type DRUG

ISIS 681257 solution for SC injection.

Cohort D: ISIS 681257: 20 mg Q2W

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.

Group Type EXPERIMENTAL

ISIS 681257

Intervention Type DRUG

ISIS 681257 solution for SC injection.

Cohort E: ISIS 681257: 20 mg QW

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.

Group Type EXPERIMENTAL

ISIS 681257

Intervention Type DRUG

ISIS 681257 solution for SC injection.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sterile normal saline (0.9% NaCl)

Interventions

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ISIS 681257

ISIS 681257 solution for SC injection.

Intervention Type DRUG

Placebo

Sterile normal saline (0.9% NaCl)

Intervention Type DRUG

Other Intervention Names

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AKCEA-APO(a)-LRx, IONIS-APO(a)-LRx, TQJ230 and Pelacarsen

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Akcea Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Site

Cottonwood, Arizona, United States

Site Status

Clinical Site

Huntington Beach, California, United States

Site Status

Clinical Site

La Jolla, California, United States

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Clinical Site

Los Angeles, California, United States

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Clinical Site

Stanford, California, United States

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Colorado Springs, Colorado, United States

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Boca Raton, Florida, United States

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Clinical Site

Jacksonville, Florida, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Cooperstown, New York, United States

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New York, New York, United States

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New York, New York, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Lancaster, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Houston, Texas, United States

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Falls Church, Virginia, United States

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Milwaukee, Wisconsin, United States

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Ottawa, , Canada

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Herlev, , Denmark

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Viborg, , Denmark

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Berlin, , Germany

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Cologne, , Germany

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Clinical Site

Amsterdam, , Netherlands

Site Status

Countries

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United States Canada Denmark Germany Netherlands

References

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Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.

Reference Type DERIVED
PMID: 39331470 (View on PubMed)

Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, Dzobo KE, Cupido AJ, Tsimikas S, Stroes ESG, de Winther MPJ, Bahjat M. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-2271. doi: 10.1093/eurheartj/ehaa171.

Reference Type DERIVED
PMID: 32268367 (View on PubMed)

Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, Shapiro MD, Stroes ES, Moriarty PM, Nordestgaard BG, Xia S, Guerriero J, Viney NJ, O'Dea L, Witztum JL; AKCEA-APO(a)-LRx Study Investigators. Lipoprotein(a) Reduction in Persons with Cardiovascular Disease. N Engl J Med. 2020 Jan 16;382(3):244-255. doi: 10.1056/NEJMoa1905239. Epub 2020 Jan 1.

Reference Type DERIVED
PMID: 31893580 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003373-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 681257-CS6

Identifier Type: -

Identifier Source: org_study_id