Clinical trial NCT03070782: Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease
Official title: A Randomized, Double-blind, Placebo-Controlled, Dose-Ranging Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) Administered Subcutaneously to Patients With Hyperlipoproteinemia(a) and Established Cardiovascular Disease (CVD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Elevated Lipoprotein(a)
Cardiovascular Disease
Keywords: IONIS-APO(a)-LRx
AKCEA-APO(a)-LRx
Dyslipidemia
Dyslipoproteinemia
Hyperlipidemia
Hyperlipoproteinemia
Hyperlipoproteinemia(a)
Hyperlipoproteinemia a
Lipoprotein
Lipoprotein(a)
Lipoprotein a
Lp(a)
Lp a
Lead sponsor: Akcea Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2017-03-06
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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

Primary outcomes:
measure: Percent Change From Baseline in Fasting Lipoprotein A [Lp(a)] at the Primary Analysis Time Point
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 16 weeks post treatment period (up to approximately 1.3 years)
measure: Number of Participants With TEAEs by Maximum Severity
timeFrame: Up to 16 weeks post treatment period (up to approximately 1.3 years)
measure: Number of Participants With TEAEs Leading to Study Discontinuation
timeFrame: Up to 16 weeks post treatment period (up to approximately 1.3 years)
Secondary outcomes:
measure: Percent Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Percentage of Participants Who Achieved Plasma Lp(a) ≤ 125 Nanomoles Per Liter (Nmol/L) or ≤ 50 Milligrams Per Deciliter (mg/dL)
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Percentage of Participants Who Achieved Plasma Lp(a) ≤ 75 Nmol/L or ≤ 30 mg/dL
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Percent Change From Baseline in the Plasma Levels of Apolipoprotein B (apoB)
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein(a) [OxPL-apo(a)]
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
measure: Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein B (OxPL-apoB)
timeFrame: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)
Other outcomes:
measure: To Evaluate Plasma Cmax of ISIS 681257 Across Different Doses and Dose Regimens.
timeFrame: 6 months
measure: To Evaluate Plasma Tmax of ISIS 681257 Across Different Doses and Dose Regimens.
timeFrame: 6 months
measure: To Evaluate Plasma AUC Values of ISIS 681257 Across Different Doses and Dose Regimens.
timeFrame: 6 months
Locations:
city: Cottonwood
country: United States
facility: Clinical Site
state: Arizona
city: Huntington Beach
country: United States
facility: Clinical Site
state: California
city: La Jolla
country: United States
facility: Clinical Site
state: California
city: Los Angeles
country: United States
facility: Clinical Site
state: California
city: Stanford
country: United States
facility: Clinical Site
state: California
city: Colorado Springs
country: United States
facility: Clinical Site
state: Colorado
city: Boca Raton
country: United States
facility: Clinical Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Site
state: Florida
city: Kansas City
country: United States
facility: Clinical Site
state: Kansas
city: Baltimore
country: United States
facility: Clinical Site
state: Maryland
city: Boston
country: United States
facility: Clinical Site
state: Massachusetts
city: Cooperstown
country: United States
facility: Clinical Site
state: New York
city: New York
country: United States
facility: Clinical Site
state: New York
city: New York
country: United States
facility: Clinical Site
state: New York
city: Cleveland
country: United States
facility: Clinical Site
state: Ohio
city: Portland
country: United States
facility: Clinical Site
state: Oregon
city: Lancaster
country: United States
facility: Clinical Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Site
state: Pennsylvania
city: Providence
country: United States
facility: Clinical Site
state: Rhode Island
city: Houston
country: United States
facility: Clinical Site
state: Texas
city: Falls Church
country: United States
facility: Clinical Site
state: Virginia
city: Milwaukee
country: United States
facility: Clinical Site
state: Wisconsin
city: Chicoutimi
country: Canada
facility: Clinical Site
state: Quebec
city: Montreal
country: Canada
facility: Clinical Site
state: Quebec
city: Montréal
country: Canada
facility: Clinical Site
state: Quebec
city: Québec
country: Canada
facility: Clinical Site
state: Quebec
city: Ottawa
country: Canada
facility: Clinical Site
city: Herlev
country: Denmark
facility: Clinical Site
city: Viborg
country: Denmark
facility: Clinical Site
city: Berlin
country: Germany
facility: Clinical Site
city: Cologne
country: Germany
facility: Clinical Site
city: Amsterdam
country: Netherlands
facility: Clinical Site
Study officials:
References:
citation: 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.
citation: 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.