Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia
SHASTA-10
A Phase 3 Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia (SHASTA-10 Study)
1 other identifier
interventional
710
24 countries
253
Brief Summary
This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG). Each participant must have completed all required visits per protocol in the parent study AROAPOC3-2003 (USA and Canada participants only; NCT# 05413135), AROAPOC3-3001(Canada and Japan participants only; NCT05089084), AROAPOC3-3003 (NCT06347003), AROAPOC3-3004 (NCT06347016) or AROAPOC3-3009 (Argentina, Italy, South Africa, and Spain; NCT06347133). Subjects who previously met all eligibility requirements for AROAPOC3-3003 or AROAPOC3-3004 and were not permitted to proceed to randomization per the Sponsor's direction in order to prevent excessive over-enrollment may also be enrolled in this trial. The subjects must meet all other applicable eligibility criteria prior to enrollment and have an HbA1c results of \<=10% within 30 days prior to Day 1. Subjects entering this OLE from AROAPOC3-2003 must meet the following additional criteria to be considered for enrollment in addition to applicable eligibility criteria:
- 1.HbA1c ≤10% within 30 days prior to Day 1
- 2.Completed AROAPOC3-2001 prior to entry into AROAPOC3-2003 AND fulfill either (c) or (d)
- 3.Baseline fasting TG level of ≥500 mg/dL and prior history of acute pancreatitis at the time of enrollment into AROAPOC3-2001
- 4.Baseline fasting TG level of ≥1000 mg/dL at the time of enrollment into AROAPOC3-2001
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2025
Typical duration for phase_3
253 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
February 7, 2025
CompletedFirst Posted
Study publicly available on registry
February 12, 2025
CompletedStudy Start
First participant enrolled
April 9, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2028
October 1, 2026
September 1, 2026
3.2 years
February 7, 2025
September 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
From first dose of study drug through Month 24
Secondary Outcomes (20)
Change from Baseline Over Time in Fasting Serum Triglyceride (TG) Levels
From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Fasting Serum TG Levels
From first dose of study drug through Month 24
Change from Baseline Over Time in Apolipoprotein CIII (APOC3)
From first dose of study drug through Month 24
Percent Change from Baseline Over Time in APOC3
From first dose of study drug through Month 24
Change from Baseline Over Time in Remnant Cholesterol
From first dose of study drug through Month 24
- +15 more secondary outcomes
Study Arms (1)
Plozasiran Injection
EXPERIMENTAL8 doses of plozasiran (ARO-APOC3) administered by subcutaneous (SC) injection
Interventions
Eligibility Criteria
You may qualify if:
- Adult males, or nonpregnant (who do not plan to become pregnant), nonlactating adult females, who are able and willing to provide written informed consent prior to the performance of any study-specific procedures
- Completed all required study visits per protocol in the parent study
- Female subjects of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 90 days after the End of Study (EOS) or the last dose of plozasiran, whichever is later. Male subjects must agree to use a condom during the study and for at least 90 days after the EOS or last dose of plozasiran whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days after the EOS or last dose of plozasiran, whichever is later. Female subjects of childbearing potential on hormonal contraceptives must be stable on medication for \>1 menstrual cycle prior to Day 1.
- Subjects 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)
- If the subject has a medical history of clinical atherosclerotic cardiovascular disease (ASCVD) or elevated 10-year ASCVD risk (eg, ≥7.5% per American Heart Association/American College of Cardiology \[AHA/ACC\] risk calculator for subjects ≥40 years of age or Framingham risk score calculator for subjects under the age of 40), the subject must be on appropriate lipid-lowering therapy as per local standard of care (ie, including moderate-to-high intensity statin, as indicated).
- If the subject has diabetes:
- Subject must be on optimized antidiabetic regimen as defined by the local standards, Investigator, and institutional practices
- Subject must have no events of diabetic ketoacidosis, diabetic decompensation/ hyperosmolar hyperglycemic nonketotic coma, diabetes complications, recurrent infections, or hospitalization related to poor glycemic control within 24 weeks of the Day 1 visit - Willing to follow diet counseling and maintain a stable low-fat diet
- HbA1c ≤10% within 30 days prior to Day 1
- Completed AROAPOC3-2001 prior to entry into AROAPOC3-2003 AND either (c) or (d) below:
- Baseline fasting TG level of ≥500 mg/dL and prior history of acute pancreatitis at the time of enrollment into AROAPOC3-2001
- Baseline fasting TG level of ≥1000 mg/dL at the time of enrollment into AROAPOC3-2001
You may not qualify if:
- Subject was permanently discontinued from receiving plozasiran in the parent study due to elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or due to HbA1c elevation that did not respond to antidiabetic regimen
- Subject withdrew consent for continued study treatment in the parent study
- Known hypersensitivity to the active substance or to any of the excipients of plozasiran
- Known hypersensitivity to the active substance or to any of the excipients of plozasiran
- Any new condition or worsening of existing condition or any other situation that in the Investigator's judgment, would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements, or put the subject at an additional safety risk
- Unwilling to limit alcohol consumption to within moderate limits for the duration of the study.
- Poorly controlled glycemia (ie, HbA1c \>10%) based upon the most recent HbA1c level reported in the parent trial prior to Day 1
- Acute pancreatitis within 4 weeks prior to Day 1
- Use of any hepatocyte-targeted siRNA that targets lipids and/or triglycerides within 365 days before Day 1 (except plozasiran or inclisiran, which are permitted). Administration of inclisiran must be separated from administration of plozasiran by at least 4 weeks throughout the treatment period
- 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 PK, whichever is longer.
- Use of an investigational agent (other than plozasiran) or device within 30 days or within 5 half-lives, based on plasma PK, whichever is longer, prior to Day 1 (V1) or current participation in an interventional investigational study.
- Recent unstable or symptomatic cardiac arrhythmia (including any associated medication changes) within 90 days prior to Day 1. Individuals with stable well-controlled atrial arrhythmias will be allowed to participate in the study.
- Uncontrolled hypertension (ie, seated systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg) at Day 1; subject may be re-evaluated when hypertension is controlled.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (253)
Research Site 21
Bakersfield, California, 93311, United States
Research Site 9
Beverly Hills, California, 90211, United States
Research Site 11
Canoga Park, California, 91303, United States
Research Site 40
Garden Grove, California, 92844, United States
Research Site 235
Huntington Beach, California, 92648, United States
Research Site 236
Lake Forest, California, 92630, United States
Research Site 39
Lincoln, California, 95648, United States
Research Site 34
Oxnard, California, 93030, United States
Research Site 229
Palm Springs, California, 92262, United States
Research Site 275
Redding, California, 96001, United States
Research Site 14
Hialeah, Florida, 33016, United States
Research Site 154
Miami, Florida, 33144, United States
Research Site 1
Miami Lakes, Florida, 33014, United States
Research Site 42
Mt. Dora, Florida, 32757, United States
Research Site 41
Orlando, Florida, 32825, United States
Research Site 16
Tamarac, Florida, 33321, United States
Research Site 18
Tampa, Florida, 33614, United States
Research Site 237
Lawrenceville, Georgia, 30044, United States
Research Site 17
Park Ridge, Illinois, 60068, United States
Research Site 43
Elkhart, Indiana, 46514, United States
Research Site 157
Indianapolis, Indiana, 46290, United States
Research Site 28
Overland Park, Kansas, 66211, United States
Research Site 23
Topeka, Kansas, 66606, United States
Research Site 12
Annapolis, Maryland, 21401, United States
Research Site 44
Baltimore, Maryland, 21229, United States
Research Site 30
Flint, Michigan, 48532, United States
Research Site 290
Minneapolis, Minnesota, 55455, United States
Research Site 33
Jackson, Mississippi, 39202, United States
Research Site 32
Olive Branch, Mississippi, 38654, United States
Research Site 2
Jefferson City, Missouri, 65109, United States
Research Site 232
St Louis, Missouri, 63136, United States
Research Site 29
Fremont, Nebraska, 68025, United States
Research Site 3
Omaha, Nebraska, 68144, United States
Research Site 77
Summit, New Jersey, 07901, United States
Research Site 72
Long Island City, New York, 11106, United States
Research Site 233
New York, New York, 10016, United States
Research Site 228
New York, New York, 10029, United States
Research Site 273
Riverhead, New York, 12401, United States
Research Site 37
Asheboro, North Carolina, 27203, United States
Research Site 36
Morehead City, North Carolina, 28557, United States
Research Site 169
Wilmington, North Carolina, 28401, United States
Research Site 22
Beavercreek, Ohio, 45431, United States
Research Site 234
Columbus, Ohio, 43214, United States
Research Site 294
Vandalia, Ohio, 45377, United States
Research Site 76
Norman, Oklahoma, 73072, United States
Research Site 31
Oklahoma City, Oklahoma, 73112, United States
Research Site
Oklahoma City, Oklahoma, 73135, United States
Research Site 26
Horsham, Pennsylvania, 19044, United States
Research Site 8
Newport, Pennsylvania, 17074, United States
Research Site 231
Philadelphia, Pennsylvania, 19104, United States
Research Site 238
Fort Mill, South Carolina, 29707, United States
Research Site 293
Chattanooga, Tennessee, 37411, United States
Research Site 27
El Paso, Texas, 79905, United States
Research Site 160
Fort Worth, Texas, 76132, United States
Research Site 272
Houston, Texas, 77030, United States
Research Site 292
Houston, Texas, 77030, United States
Research Site 73
Houston, Texas, 77061, United States
Research Site 291
Houston, Texas, 77074, United States
Research Site 75
Houston, Texas, 77090, United States
Research Site 24
Houston, Texas, 77095, United States
Research Site 230
Missouri City, Texas, 77459, United States
Research Site 74
Plano, Texas, 75093, United States
Research Site 13
Sugar Land, Texas, 77479, United States
Research Site 170
Tomball, Texas, 77375, United States
Research Site 25
Victoria, Texas, 77901, United States
Research Site 15
Bountiful, Utah, 84010, United States
Research Site 35
St. George, Utah, 84790, United States
Research Site 10
Manassas, Virginia, 20110, United States
Research Site 274
Seattle, Washington, 98109, United States
Research Site 250
Ciudad Autonoma Buenos Aires, Buenos Aires, C1128AAF, Argentina
Research Site 251
Ramos Mejía, Buenos Aires, B1704ETD, Argentina
Research Site 277
Buenos Aires, C1056ABI, Argentina
Research Site 172
Ciudad Autonoma Buenos Aires, 1425, Argentina
Research Site 276
Ciudad Autonoma Buenos Aires, C1417, Argentina
Research Site 173
Ciudad Autonoma Buenos Aires, C1430CKE, Argentina
Research Site 278
Córdoba, 5000, Argentina
Research Site 171
Córdoba, X5000AAW, Argentina
Research Site 239
Córdoba, X5006CBI, Argentina
Research Site 240
Córdoba, X5008HHW, Argentina
Research Site 249
Rosario, 2000, Argentina
Research Site 86
Box Hill, Victoria, 3128, Australia
Research Site 253
Clayton, Victoria, 3168, Australia
Research Site 252
Heidelberg Heights, Victoria, 3081, Australia
Research Site 174
Nedlands, Western Australia, 6009, Australia
Research Site 48
Gozée, 6534, Belgium
Research Site 87
Hasselt, 3500, Belgium
Research Site 90
Mechelen, 97770, Belgium
Research Site 46
Namur, 5000, Belgium
Research Site 89
Namur, 5380, Belgium
Research Site 175
Roeselare, 8800, Belgium
Research Site 45
Wetteren, 9230, Belgium
Research Site 259
Salvador, Estado de Bahia, 41810-010, Brazil
Research Site 257
Brasília, Federal District, 70710-100, Brazil
Research Site 178
Belo Horizonte, Minas Gerais, 30150-274, Brazil
Research Site 255
Belo Horizonte, Minas Gerais, 30220-140, Brazil
Research Site 254
Belém, Pará, 66073-000, Brazil
Research Site 256
Canoas, Rio Grande do Sul, 92425-900, Brazil
Research Site 181
Aracaju, Sergipe, 49055-530, Brazil
Research Site 180
Campinas, São Paulo, 13060-080, Brazil
Research Site 176
Votuporanga, São Paulo, 15500-269, Brazil
Research Site 279
Campina Grande do Sul, 83430-000, Brazil
Research Site 296
Paranã, 80730-150, Brazil
Research Site 281
Salvador, 40170310, Brazil
Research Site 280
Salvador, 40323-010, Brazil
Research Site 177
São Paulo, 04266-010, Brazil
Research Site 179
São Paulo, 05403-900, Brazil
Research Site 187
Burgas, 8000, Bulgaria
Research Site 100
Dimitrovgrad, 6400, Bulgaria
Research Site 98
Kardzhali, 6600, Bulgaria
Research Site 52
Kyustendil, 2500, Bulgaria
Research Site 49
Pleven, 5800, Bulgaria
Research Site 185
Plovdiv, 4001, Bulgaria
Research Site 50
Plovdiv, 4002, Bulgaria
Research Site 94
Rousse, 7013, Bulgaria
Research Site 53
Sofia, 1404, Bulgaria
Research Site 182
Sofia, 1431, Bulgaria
Research Site 186
Sofia, 1431, Bulgaria
Research Site 282
Sofia, 1510, Bulgaria
Research Site 184
Sofia, 1527, Bulgaria
Research Site 260
Sofia, 1582, Bulgaria
Research Site 51
Sofia, 1616, Bulgaria
Research Site 97
Sofia, 1618, Bulgaria
Research Site 283
Sofia, 1756, Bulgaria
Research Site 99
Stara Zagora, 6010, Bulgaria
Research Site 20
Victoria, British Columbia, V8T5G4, Canada
Research Site 103
Halifax, Nova Scotia, NS B3H 1V7, Canada
Research Site 7
London, Ontario, N6A 5K8, Canada
Research Site 55
Sarnia, Ontario, N7T 4X3, Canada
Research Site 241
Toronto, Ontario, M5G 2C4, Canada
Research Site 102
Waterloo, Ontario, N2T 0C1, Canada
Research Site 6
Chicoutimi, Quebec, G7H 7K9, Canada
Research Site 5
Montreal, Quebec, H2W 1R7, Canada
Research Site 4
Québec, Quebec, G1V 4W2, Canada
Research Site 56
Kitchener, N2H5Z8, Canada
Research Site 19
Québec, G1G5X1, Canada
Research Site 191
Bengbu, Anhui, 233004, China
Research Site 104
Beijing, Beijing Municipality, 100034, China
Research Site 193
Beijing, Beijing Municipality, 100091, China
Research Site 62
Guangzhou, Guangdong, 510000, China
Research Site 111
Guangzhou, Guangdong, 510180, China
Research Site 63
Liuzhou, Guangxi Zhuang, 545006, China
Research Site 106
Xingtai, Hebei, 054099, China
Research Site 188
Luoyang, Henan, 471003, China
Research Site 59
Changsha, Hu'nan, 410011, China
Research Site 108
Changsha, Hu'nan, 410015, China
Research Site 261
Wuhan, Hubei, 430060, China
Research Site 115
Baotou, Inner Mongolia, 014010, China
Research Site 192
Suzhou, Jiangsu, 215002, China
Research Site 61
Nanchang, Jiangxi, 330006, China
Research Site 190
Liaocheng, Shandong, 252000, China
Research Site 243
Shanghai, Shanghai Municipality, 200040, China
Research Site 189
Shanghai, Shanghai Municipality, 200050, China
Research Site 105
Yuncheng, Shanxi, 44000, China
Research Site 113
Chengdu, Sichuan, 610072, China
Research Site 242
Tianjin, Tianjin Municipality, 300121, China
Research Site 60
Wenzhou, Zhejiang, 325000, China
Research Site 295
Beijing, 100730, China
Research Site 262
Karlovac, 47000, Croatia
Research Site 194
Zagreb, 10000, Croatia
Research Site 65
Hodonín, 69501, Czechia
Research Site 197
Hradec Králové, 50005, Czechia
Research Site 264
Náchod, 547 01, Czechia
Research Site 118
Olomouc, CZ77900, Czechia
Research Site 119
Prague, 11000, Czechia
Research Site 66
Prague, 11000, Czechia
Research Site 244
Prague, 140 21, Czechia
Research Site 116
Praha 4-Krc, 140 59, Czechia
Research Site 263
Slaný, 27401, Czechia
Research Site 198
Teplice, 41501, Czechia
Research Site 196
Trutnov, 541 01, Czechia
Research Site 195
Ústí nad Labem, 40113, Czechia
Research Site 199
Marseille, Bouches-du-Rhône, 13005, France
Research Site 120
Pessac, Gironde, 33604, France
Research Site 200
Paris, Paris, 75013, France
Research Site 201
Magdeburg, Saxony-Anhalt, 39120, Germany
Research Site 285
Berlin, 13353, Germany
Research Site 284
Deggingen, 73326, Germany
Research Site 204
Budapest, 1033, Hungary
Research Site 123
Budapest, 1051, Hungary
Research Site 68
Budapest, 1132, Hungary
Research Site 265
Budapest, 1152, Hungary
Research Site 205
Miskolc, 3530, Hungary
Research Site 67
Pécs, 7623, Hungary
Research Site 286
Szeged, 6725, Hungary
Research Site 202
Veszprém, 8200, Hungary
Research Site 203
Zalaegerszeg, 8900, Hungary
Research Site 209
Rozzano, Milano, 20089, Italy
Research Site 245
Bologna, 40138, Italy
Research Site 208
Brescia, 25123, Italy
Research Site 207
Milan, 20162, Italy
Research Site 210
Palermo, 90127, Italy
Research Site 206
Roma, 00168, Italy
Research Site
Shimotsuke-shi, Tochigi, 329-0498, Japan
Research Site
Bunkyo-Ku, Tokyo, 113-0033, Japan
Research Site
Chiba, 260-8677, Japan
Research Site 212
Daugavpils, LV-5410, Latvia
Research Site 124
Daugavpils, LV-5417, Latvia
Research Site 211
Riga, LV-1002, Latvia
Research Site 287
Riga, LV-1038, Latvia
Research Site 69
Riga, LV1063, Latvia
Research Site 70
Kaunas, 49387, Lithuania
Research Site 246
Kaunas, 49449, Lithuania
Research Site 213
Kaunas, LT-50177, Lithuania
Research Site 127
Šiauliai, LT-76206, Lithuania
Research Site 214
Vilnius, LT-08661, Lithuania
Research Site 128
Christchurch, 08011, New Zealand
Research Site 129
Wellington, 6021, New Zealand
Research Site 78
Elblag, 82-300, Poland
Research Site 247
Gdynia, 81-338, Poland
Research Site 81
Katowice, 40-156, Poland
Research Site 141
Katowice, 40-752, Poland
Research Site 85
Katowice, 40-752, Poland
Research Site 83
Krakow, 31-501, Poland
Research Site 136
Lodz, 91-363, Poland
Research Site 131
Lodz, 94-255, Poland
Research Site 79
Lodz, 94-255, Poland
Research Site 80
Malbork, 82-200, Poland
Research Site 135
Szczecin, 71- 500, Poland
Research Site 84
Warsaw, 00-215, Poland
Research Site 216
Warsaw, 03-291, Poland
Research Site 267
Wroclaw, 53-030, Poland
Research Site 215
Zamość, 22-400, Poland
Research Site 82
Żarów, 58-130, Poland
Research Site 142
Bucharest, 010192, Romania
Research Site 217
Galati, 800291, Romania
Research Site 143
Ploieşti, 100342, Romania
Research Site 144
Târgu Mureş, 540136, Romania
Research Site 145
Timișoara, 300362, Romania
Research Site 268
Banská Bystrica, 97401, Slovakia
Research Site 147
Bardejov, 08501, Slovakia
Research Site 146
Košice, 04001, Slovakia
Research Site 218
Moldava nad Bodvou, 045 01, Slovakia
Research Site 248
Nitra, 950 01, Slovakia
Research Site 148
Rožňava, 048 01, Slovakia
Research Site 219
Krugersdorp, Gauteng, 1739, South Africa
Research Site 270
Pretoria, Gauteng, 0181, South Africa
Research Site 222
Cape Town, Western Cape, 7500, South Africa
Research Site 220
Cape Town, Western Cape, 7570, South Africa
Research Site 221
Cape Town, Western Cape, 7925, South Africa
Research Site 269
Mossel Bay, Western Cape, 6500, South Africa
Research Site 149
Somerset West, Western Cape, 7130, South Africa
Research Site 288
Cape Town, 7530, South Africa
Research Site 224
A Coruña, La Coruña, 15006, Spain
Research Site 271
Barcelona, 08023, Spain
Research Site 223
Barcelona, 08035, Spain
Research Site 226
Madrid, 28041, Spain
Research Site 289
Santiago de Compostela, 15706, Spain
Research Site 150
Seville, 41013, Spain
Research Site 225
Valencia, 46010, Spain
Research Site 151
Zaragoza, 50009, Spain
Research Site 71
Plymouth, Devon, PL5 3JB, United Kingdom
Research Site 153
Torquay, Devon, TQ2 7AA, United Kingdom
Research Site 227
London, Greater London, EC1M 6BQ, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 7, 2025
First Posted
February 12, 2025
Study Start
April 9, 2025
Primary Completion (Estimated)
July 1, 2028
Study Completion (Estimated)
July 1, 2028
Last Updated
October 1, 2026
Record last verified: 2026-09
Data Sharing
- IPD Sharing
- Will not share