Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia
SHASTA-3
Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia
2 other identifiers
interventional
446
17 countries
196
Brief Summary
This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2024
196 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2024
CompletedFirst Posted
Study publicly available on registry
April 4, 2024
CompletedStudy Start
First participant enrolled
July 22, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2026
October 27, 2025
October 1, 2025
1.9 years
March 29, 2024
October 24, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo
Baseline, Month 12
Secondary Outcomes (20)
Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo
Baseline, Month 10
Proportion of Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 12 Compared to Placebo
Baseline, Month 12
Proportion of Participants Who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 12 Compared to Placebo
Baseline, Month 12
Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 compared to placebo
Baseline, Month 12
Percent change in non-HDL-C from baseline to Month 12 compared to placebo
Baseline, Month 12
- +15 more secondary outcomes
Study Arms (2)
Plozasiran Injection
EXPERIMENTAL4 doses of plozasiran (ARO-APOC3) by subcutaneous (sc) injection
Placebo
PLACEBO COMPARATORcalculated volume to match active treatment by sc injection
Interventions
Eligibility Criteria
You may qualify if:
- Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening
- Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/L)
- Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
- Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
- Screening HbA1C ≤9.0%
- Willing to follow diet counseling and maintain a stable low-fat diet
- Must be on standard of care lipid and TG lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or due to a previous adverse reaction associated with, attributed to, or caused by specific drug)
You may not qualify if:
- Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks
- Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer
- Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1-causing genes
- Acute pancreatitis within 4 weeks prior to screening
- Body mass index \>45kg/m\^2
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (196)
Research Center 1
Garden Grove, California, 92844, United States
Research Center 2
Lake Forest, California, 92630, United States
Research Center 3
Montclair, California, 91763, United States
Research Center 4
Panorama City, California, 91402, United States
Research Center 5
Redding, California, 96001, United States
Research Center 6
Colorado Springs, Colorado, 80909, United States
Research Center 7
Hialeah, Florida, 33016, United States
Research Center 8
Lake City, Florida, 32055, United States
Research Center 9
Miami Lakes, Florida, 33014, United States
Research Center 10
Mt. Dora, Florida, 32757, United States
Research Center 11
Orlando, Florida, 32825, United States
Research Center 12
Pensacola, Florida, 32503, United States
Research Center 13
Tamarac, Florida, 33321, United States
Research Center 14
Tampa, Florida, 33614, United States
Research Center 15
Macon, Georgia, 31210, United States
Research Center 16
Savannah, Georgia, 31401, United States
Research Center 17
Park Ridge, Illinois, 60068, United States
Research Center 18
Eunice, Louisiana, 70535, United States
Research Center 19
Baltimore, Maryland, 21229, United States
Research Center 20
Flint, Michigan, 48532, United States
Research Center 21
Minneapolis, Minnesota, 55455, United States
Research Center 22
Olive Branch, Mississippi, 38654, United States
Research Center 23
Jefferson City, Missouri, 65109, United States
Research Center 24
St Louis, Missouri, 63136, United States
Research Center 26
Omaha, Nebraska, 68114, United States
Research Center 25
Omaha, Nebraska, 68144, United States
Research Center 27
Las Vegas, Nevada, 89119, United States
Research Center 29
Long Island City, New York, 11106, United States
Research Center 30
New York, New York, 10016, United States
Research Center 31
Rochester, New York, 14642, United States
Research Center 28
The Bronx, New York, 10455, United States
Research Center 32
Vestal, New York, 13850, United States
Research Center 33
Morehead City, North Carolina, 28557, United States
Research Center 34
Winston-Salem, North Carolina, 27157, United States
Research Center 35
Cincinnati, Ohio, 45219, United States
Research Center 36
Columbus, Ohio, 43210, United States
Research Center 37
Norman, Oklahoma, 73072, United States
Research Center 38
Oklahoma City, Oklahoma, 73111, United States
Research Center 39
Powell, Tennessee, 37849, United States
Research Center 40
El Paso, Texas, 79905, United States
Research Center 47
Houston, Texas, 77029, United States
Research Center 45
Houston, Texas, 77030, United States
Research Center 46
Houston, Texas, 77030, United States
Research Center 42
Houston, Texas, 77061, United States
Research Center 44
Houston, Texas, 77074, United States
Research Center 43
Houston, Texas, 77079, United States
Research Center 41
Houston, Texas, 77095, United States
Research Center 48
Laredo, Texas, 78041, United States
Research Center 49
Missouri City, Texas, 77459, United States
Research Center 50
Plano, Texas, 75093, United States
Research Center 51
San Antonio, Texas, 78230, United States
Research Center 52
Seattle, Washington, 98109, United States
Research Center 8
Ramos Mejía, Buenos Aires, B1704ETD, Argentina
Research Center 10
San Isidro, Buenos Aires, 1642, Argentina
Research Center 7
Temperley, Buenos Aires, B1834GUK, Argentina
Research Center 4
Córdoba, Córdoba Province, 5000, Argentina
Research Center 9
Córdoba, Córdoba Province, 5008, Argentina
Research Center 5
Córdoba, Córdoba Province, X5000AAW, Argentina
Research Center 3
Córdoba, Córdoba Province, X5006CBI, Argentina
Research Center 6
Buenos Aires, C1417, Argentina
Research Center 2
Buenos Aires, C1425AGC, Argentina
Research Center 1
Buenos Aires, C1430, Argentina
Research Center 1
Blacktown, New South Wales, 2148, Australia
Research Center 4
Concord, New South Wales, 2139, Australia
Research Center 5
Merewether, New South Wales, 2291, Australia
Research Center 2
Box Hill, Victoria, 3138, Australia
Research Center 7
Clayton, Victoria, 3168, Australia
Research Center 3
Heidelberg, Victoria, 3084, Australia
Research Center 6
Crawley, Western Australia, 6009, Australia
Research Center 4
Gozée, 6534, Belgium
Research Center 6
Hasselt, 3500, Belgium
Research Center 3
Mechelen, 2800, Belgium
Research Center 2
Namur, 5101, Belgium
Research Center 5
Roeselare, 8800, Belgium
Research Center 1
Wetteren, 9230, Belgium
Research Center 10
Vitória, Espírito Santo, 29055-450, Brazil
Research Center 12
Salvador, Estado de Bahia, 40050-410, Brazil
Research Center 13
Salvador, Estado de Bahia, 40323-010, Brazil
Research Center 14
Salvador, Estado de Bahia, 41810-010, Brazil
Research Center 5
Belo Horizonte, Minas Gerais, 30220-140, Brazil
Research Center 8
Campina Grande do Sul, Paraná, 83430-000, Brazil
Research Center 2
Curitiba, Paraná, 80730-150, Brazil
Research Center 4
Belém, Pará, 66073-000, Brazil
Research Center 6
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Research Center 9
Porto Alegre, Rio Grande do Sul, 90430-001, Brazil
Research Center 1
Campinas, São Paulo, 13083-190, Brazil
Research Center 7
São Paulo, São Paulo, 04266-010, Brazil
Research Center 11
São Paulo, São Paulo, 05403-000, Brazil
Research Center 3
Votuporanga, São Paulo, 15501-405, Brazil
Research Center 8
Burgas, Burgas, 8000, Bulgaria
Research Center 11
Rousse, Ruse, 7000, Bulgaria
Research Center 15
Sofia, Sofia, 1527, Bulgaria
Research Center 7
Sofia, Sofia, 1527, Bulgaria
Research Center 12
Blagoevgrad, 2700, Bulgaria
Research Center 10
Kardzhali, 6600, Bulgaria
Research Center 1
Pleven, 5800, Bulgaria
Research Center 3
Pleven, 5800, Bulgaria
Research Center 4
Plovdiv, 4001, Bulgaria
Research Center 2
Plovdiv, 4002, Bulgaria
Research Center 9
Plovdiv, 4004, Bulgaria
Research Center 13
Sofia, 1336, Bulgaria
Research Center 6
Sofia, 1404, Bulgaria
Research Center 5
Sofia, 1431, Bulgaria
Research Center 14
Sofia, 1680, Bulgaria
Research Center 3
Victoria, British Columbia, V8T 5G4, Canada
Research Center 1
Brampton, Ontario, L6S 0C6, Canada
Research Center 8
London, Ontario, N6A 5A5, Canada
Research Center 2
Sarnia, Ontario, N7T 4X3, Canada
Research Center 5
Waterloo, Ontario, N2TOC1, Canada
Research Center 6
Montreal, Quebec, H2W 1R7, Canada
Research Center 4
Québec, Quebec, G1V 4W2, Canada
Research Center 7
Halifax, B3H 1V7, Canada
Research Center 11
Bengbu, Anhui, 233004, China
Research Center 23
Beijing, Beijing Municipality, 100191, China
Research Center 22
Beijing, Beijing Municipality, 100730, China
Research Center 7
Guangzhou, Guangdong, 510180, China
Research Center 19
Guanzhou, Guangdong, 510080, China
Research Center 8
Liuchow, Guangxi Zhuang, 545006, China
Research Center 13
Xingtai, Hebei, 054099, China
Research Center 6
Luoyang, Henan, 471003, China
Research Center 21
Wuhan, Hubei, 430060, China
Research Center 4
Changsha, Hunan, 410011, China
Research Center 18
Changsha, Hunan, 410015, China
Research Center 16
Baotou, Inner Mongolia, 14010, China
Research Center 10
Suzhou, Jiangsu, 215002, China
Research Center 9
Shanghai, Shanghai Municipality, 2000040, China
Research Center 12
Shanghai, Shanghai Municipality, 200050, China
Research Center 2
Yuncheng, Shanxi, 44000, China
Research Center 17
Chengdu, Sichuan, 610072, China
Research Center 20
Tianjin, Tianjin Municipality, 300121, China
Research Center 1
Beijing, Xicheng, 10034, China
Research Center 15
Wenzhou, Zhejiang, 325000, China
Research Center 5
Hangzhou, 311100, China
Research Center 3
Liaocheng, 252000, China
Research Center 14
Nanchang, 330006, China
Research Center 1
Zagreb, City of Zagreb, 10000, Croatia
Research Center 2
Krapinske Toplice, 49217, Croatia
Research Center 3
Zagreb, 10000, Croatia
Research Center 4
Zagreb, 10000, Croatia
Research Center 8
Prague, Prague, 140 21, Czechia
Research Center 4
Prague, Prague, 140 59, Czechia
Research Center 3
Hodonín, 69501, Czechia
Research Center 6
Hradec Králové, 50005, Czechia
Research Center 1
Ostrava, 70200, Czechia
Research Center 7
Praha 1-Nove Mesto, 11000, Czechia
Research Center 5
Praha 4-Krc, 140 59, Czechia
Research Center 2
Uherské Hradiště, 68601, Czechia
Research Center 9
Ústí nad Labem, 40113, Czechia
Research Center 1
Budapest, 1033, Hungary
Research Center 4
Budapest, 1051, Hungary
Research Center 2
Budapest, 1132, Hungary
Research Center 6
Budapest, 1152, Hungary
Research Center 3
Szeged, 6725, Hungary
Research Center 5
Veszprém, 8200, Hungary
Research Center 3
Rozzano, Milano, 20089, Italy
Research Center 2
Palermo, Sicily, 90127, Italy
Research Center 6
Bologna, 40138, Italy
Research Center 5
Brescia, 25123, Italy
Research Center 4
Milan, 20162, Italy
Research Center 1
Roma, 00168, Italy
Research Center 15
Żarów, Swidnica, 58-130, Poland
Research Center 7
Bydgoszcz, 85-231, Poland
Research Center 11
Elblag, 82-300, Poland
Research Center 10
Katowice, 40-752, Poland
Research Center 13
Krakow, 30-727, Poland
Research Center 17
Krakow, 31-202, Poland
Research Center 8
Krakow, 31-501, Poland
Research Center 12
Lodz, 91-363, Poland
Research Center 18
Warsaw, 00-215, Poland
Research Center 9
Warsaw, 03-291, Poland
Research Center 16
Wroclaw, 53-030, Poland
Research Center 14
Wroclaw, 53-673, Poland
Research Center 3
Brasov, Brașov County, 500091, Romania
Research Center 1
Bucharest, București, 010192, Romania
Research Center 2
Cluj-Napoca, Cluj, 400000, Romania
Research Center 6
Alba Iulia, Jud. Alba, 510053, Romania
Research Center 4
Ploieşti, Jud. Prahova, 100342, Romania
Research Center 5
Timișoara, Timiș County, 300362, Romania
Research Center 8
Deva, 330084, Romania
Research Center 7
Galati, 800291, Romania
Research Center 9
Târgu Mureş, 540136, Romania
Research Center 4
Banská Bystrica, Banská Bystrica Region, 97401, Slovakia
Research Center 1
Košice, Košice Region, 040 01, Slovakia
Research Center 3
Moldava nad Bodvou, Košice Region, 045 01, Slovakia
Research Center 6
Bardejov, 08501, Slovakia
Research Center 5
Bratislava, 81109, Slovakia
Research Center 2
Žilina, Žilina Region, 10010, Slovakia
Research Center 2
Barcelona, 08023, Spain
Research Center 3
Barcelona, 08035, Spain
Research Center 1
Valencia, 46010, Spain
Research Center 4
Zaragoza, 50009, Spain
Research Center 3
Torpoint, Cornwall, PL11 2TB, United Kingdom
Research Center 5
Torquay, Devon, TQ2 7AA, United Kingdom
Research Center 2
Plymouth, Devpn, PL5 3JB, United Kingdom
Research Center 1
London, EC1M 6BQ, United Kingdom
Research Center 4
London, N12 8BU, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2024
First Posted
April 4, 2024
Study Start
July 22, 2024
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
September 1, 2026
Last Updated
October 27, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will not share