Clinical trial NCT04270760: Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study
Official title: A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran (AMG 890) in Subjects With Elevated Lipoprotein(a)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Disease
Keywords: Olpasiran
AMG 890
siRNA
lipoprotein (a) Lp(a)
Cardiovascular
Cardiovascular disease
Atherosclerotic cardiovascular disease
Cholesterol
Apolipoprotein (B)
Hyperlipidemia
Dyslipidemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 281
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: Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp\[a\]).


Eligibility criteria: Inclusion Criteria:

* Age 18 to 80 years
* Lipoprotein (a) \> 150 nmol/L
* Evidence of atherosclerotic cardiovascular disease

Exclusion Criteria:

* Severe renal dysfunction
* History or clinical evidence of hepatic dysfunction
* Malignancy within the last 5 years
* Currently receiving, or less than 3 months at Day 1 since receiving \> 200 mg/day Niacin

Primary outcomes:
measure: Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36
timeFrame: Baseline and Week 36
Secondary outcomes:
measure: Percentage Change From Baseline in Lp(a) at Week 48
timeFrame: Baseline and Week 48
measure: Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48
timeFrame: Baseline; Week 36 and Week 48
measure: Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48
timeFrame: Baseline; Week 36 and Week 48
measure: Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48
timeFrame: Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Mooresville
country: United States
facility: Crossroads Clinical Research Inc
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Hurst
country: United States
facility: Protenium Clinical Research
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Milton
country: Australia
facility: Core Research Group Pty Ltd
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: Woolloongabba
country: Australia
facility: Dr Heart Pty Ltd
city: Brampton
country: Canada
facility: LMC Clinical Research Incorporated
state: Ontario
city: Concord
country: Canada
facility: LMC Clinical Research Incorporated Thornhill
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Research Institute of McGill University Health Center - Glen Site
state: Quebec
city: Quebec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Incorporated
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Herlev
country: Denmark
facility: Herlev Gentofte Hospital
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg
city: Kopavogur
country: Iceland
facility: Thjonustumidstod Rannsoknaverkefna
city: Asahi-shi
country: Japan
facility: Asahi General Hospital
state: Chiba
city: Kashiwa-shi
country: Japan
facility: The Jikei University Kashiwa Hospital
state: Chiba
city: Asahikawa-shi
country: Japan
facility: Asahikawa City Hospital
state: Hokkaido
city: Kahoku-gun
country: Japan
facility: Kanazawa Medical University Hospital
state: Ishikawa
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
state: Saitama
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: The Hague
country: Netherlands
facility: Haga Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: O'Donoghue ML, G Lopez JA, Knusel B, Gencer B, Wang H, Wu Y, Kassahun H, Sabatine MS. Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE). Am Heart J. 2022 Sep;251:61-69. doi: 10.1016/j.ahj.2022.05.004. Epub 2022 May 16.
citation: O'Donoghue ML, Rosenson RS, Gencer B, Lopez JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Ran X, Murphy SA, Wang H, Wu Y, Kassahun H, Sabatine MS; OCEAN(a)-DOSE Trial Investigators. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Engl J Med. 2022 Nov 17;387(20):1855-1864. doi: 10.1056/NEJMoa2211023. Epub 2022 Nov 6.
citation: O'Donoghue ML, Rosenson RS, Lopez JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Murphy SA, Wang H, Wu Y, Shah T, Wang J, Wilmanski T, Sohn W, Kassahun H, Sabatine MS; OCEAN(a)-DOSE Trial Investigators. The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results. J Am Coll Cardiol. 2024 Aug 27;84(9):790-797. doi: 10.1016/j.jacc.2024.05.058.
citation: Kaur G, Rosenson RS, Gencer B, Lopez JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Park JG, Wang H, Wu Y, Kassahun H, Sabatine MS, O'Donoghue ML. Olpasiran lowering of lipoprotein(a) according to baseline levels: insights from the OCEAN(a)-DOSE study. Eur Heart J. 2025 Mar 24;46(12):1162-1164. doi: 10.1093/eurheartj/ehae781. No abstract available.
citation: Rosenson RS, Lopez JAG, Gaudet D, Baum SJ, Stout E, Lepor NE, Park JG, Murphy SA, Knusel B, Wang J, Wilmanski T, Wang H, Wu Y, Kassahun H, Sabatine MS, O'Donoghue ML; OCEAN(a)-DOSE Trial Investigators. Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers: Results From the OCEAN(a)-DOSE Trial. JAMA Cardiol. 2025 May 1;10(5):482-486. doi: 10.1001/jamacardio.2024.5433.