Severe HypertriglyceridemiaPhase 3SHASTA-5NCT06880770
Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis
A Phase 3 study testing Plozasiran in people with Severe Hypertriglyceridemia, run by Arrowhead Pharmaceuticals at 140 sites in 27 countries.
Trial summary
This study will evaluate the efficacy and safety of plozasiran in approximately 288 adult participants with severe hypertriglyceridemia (SHTG) and history of at least two prior acute pancreatitis (AP) events not attributed to other etiologies, with at least one occurring within the last 12 months prior to screening. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Hypertriglyceridemia
- What is being tested?
- Plozasiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 140 sitesin 27 countries
- Study dates
- 24 Apr 2025to Jun 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males, or nonpregnant (who do not plan to become pregnant) nonlactating females
- Established diagnosis of SHTG and prior documented evidence of fasting TG levels of ≥ 880 mg/dL (≥ 10 mmol/L)
- Documented evidence of at least 1 prior AP event not attributed to other etiologies occurring within the last 60 months prior to Screening.
- Fasting low-density lipoprotein cholesterol (LDL-C) ≤ 130 mg/dL (≤ 3.37 mmol/L) at Screening
- Screening hemoglobin A1c (HbA1c) ≤ 9.5%
- 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, or a treatment failure as determined by the Investigator)
Who cannot join
- Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1, except inclisiran.
- Use of any other hepatocyte targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5 half-lives lives before day 1. Whichever is longer.
- AP ≤ 4 weeks prior to Randomization/Day 1
- Body mass index (BMI) > 45 kg/m^2
- Any planned bariatric surgery or similar procedures to induce weight lost starting at consent through End of Study (EOS)
- Planned coronary intervention (e.g. stent placement or heart bypass) during the study
Show all 16Show fewer
- History of arterial revascularization within 16 weeks of Screening
- History of acute coronary syndrome event within 24 weeks of Screening
- Recent atherosclerotic cardiovascular disease (ASCVD) event within 24 weeks of Screening
- Recent unstable or symptomatic cardiac arrhythmia (including any associated medication changes) within 90 days of Screening. Individuals with stable well-controlled atrial arrhythmia will be allowed to participate in the study
- History of pacemaker or automatic implantable cardioverter defibrillators implant within 30 days before Screening
- New York Heart Association Class III-IV heart failure or last known ejection fraction of < 30%
- Current diagnosis of nephrotic syndrome
- Chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m^2
- Liver disease defined as cirrhosis or Child-Pugh Class B and C, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5× Upper Limit of Normal (ULN) at Screening
- Note: Additional Inclusion/Exclusion Criteria may apply per protocol
Trial locations and contacts
140 sites in 27 countries. Contact the study team or a site near you to ask about taking part.
140 sites in 27 countries
China22 sites, 22 recruiting
- Recruiting
Research Center
Baotou, Inner Mongolia, 014010
- Recruiting
Research Center
Beijing, Beijing Municipality, 100730
- Recruiting
Research Site
Beijing, 100053
- Recruiting
Research Site
Ch’ang-ch’un, 130021
- Recruiting
Research Site
Changsha, 410015
- Recruiting
Research Site
Chengdu, Sichuan, 610041
- Recruiting
Research Site
Chengdu, 610074
- Recruiting
Research Site
Chifeng, Inner Mongolia, 024099
- Recruiting
Research Site
Guangzhou, Guangdong, 510080
- Recruiting
Research Site
Guiyang, Guizhou, 550000
- Recruiting
Research Center
Hangzhou, Zhejiang, 310000
- Recruiting
Research Site
Hangzhou, Zhejiang, 310003
- Recruiting
Research Site
Harbin, Heilongjiang, 150040
- Recruiting
Research Site
Luoyang, Henan, 471000
- Recruiting
Research Site
Luoyang, Henan, 471002
- Recruiting
Research Center
Nanchang, Jiangxi, 330006
- Recruiting
Research Site
Nanjing, 210002
- Recruiting
Research Site
Nanyang, Henan, 473000
- Recruiting
Research Center
Shanghai, Shanghai Municipality, 201620
- Recruiting
Research Site
Shenyang, Liaoning, 110016
- Recruiting
Research Site
Wenzhou, Zhejiang, 325000
- Recruiting
Research Site
Zhuzhou, Hunan, 412000
United States17 sites, 17 recruiting
- Recruiting
Research Site
Ann Arbor, Michigan, 48109
- Recruiting
Clinical Research Site 3
Greensboro, North Carolina, 27401
- Recruiting
Research Site
Indianapolis, Indiana, 46202
- Recruiting
Research Site
Kansas City, Kansas, 66160
- Recruiting
Research Site
Los Angeles, California, 90027
- Recruiting
Clinical Research Site 1
Mesquite, Texas, 75149
- Recruiting
Research Site
New Haven, Connecticut, 06519
- Recruiting
Research Site
New York, New York, 10029
- Recruiting
Clinical Research Site 5
North Platte, Nebraska, 69101
- Recruiting
Clinical Research Site 7
Philadelphia, Pennsylvania, 19107
- Recruiting
Research Site
Pittsburgh, Pennsylvania, 15213
- Recruiting
Clinical Research Site 2
San Antonio, Texas, 78233
- Recruiting
Clinical Research Site 4
Santa Clarita, California, 91321
- Recruiting
Research Site
Seattle, Washington, 98109
- Recruiting
Clinical Research Site 6
Springfield, Illinois, 62702
- Recruiting
Research Site
St Louis, Missouri, 63110
- Recruiting
Research Site
Wilmington, North Carolina, 28412
Brazil11 sites, 11 recruiting
- Recruiting
Research Site
Belo Horizonte, Minas Gerais, 30150-274
- Recruiting
Research Site
Belo Horizonte, Minas Gerais, 30150-320
- Recruiting
Research Site
Belo Horizonte, Minas Gerais, 30220-140
- Recruiting
Research Site
Curitiba, Paraná, 80230-130
- Recruiting
Research Site
Fortaleza, Ceará, 60430-370
- Recruiting
Research Site
Porto Alegre, Rio Grande do Sul, 90035-903
- Recruiting
Research Site
Porto Alegre, Rio Grande do Sul, 90620-001
- Recruiting
Research Site
Pôrto Alegre, Rio Grande do Sul, 90050-170
- Recruiting
Research Site
São Paulo, São Paulo, 05403-900
- Not yet recruiting
Research Site
São Paulo, São Paulo, 99999
- Recruiting
Research Site
São Paulo, 01221-020
Bulgaria9 sites, 9 recruiting
- Recruiting
Research Site
Burgas, 8000
- Recruiting
Research Site
Dimitrovgrad, 6400
- Recruiting
Research Site
Pleven, 5800
- Recruiting
Research Center
Plovdiv, 4002
- Recruiting
Research Site
Plovdiv, 4003
- Recruiting
Research Site
Rousse, 7013
- Recruiting
Research Site
Sofia, 1404
- Recruiting
Research Site
Sofia, 1431
- Recruiting
Research Site
Stara Zagora, 6000
Israel8 sites, 8 recruiting
- Recruiting
Research Site
Ashkelon, 7830604
- Recruiting
Research Site
Beersheba, 8410101
- Recruiting
Research Site
Haifa, 3109601
- Recruiting
Research Site
Jerusalem, 9103102
- Recruiting
Research Site
Petah Tikva, 4941492
- Recruiting
Research Site
Ramat Gan, 5265601
- Recruiting
Research Site
Rehovot, 7610001
- Recruiting
Research Site
Tel Aviv, 6423906
South Korea8 sites, 8 recruiting
- Recruiting
Research Site
Busan, 49201
- Recruiting
Research Site
Jeonju, Jeollabuk-do, 54907
- Recruiting
Research Site
Sejong, 30099
- Recruiting
Research Site
Seongnam-si, Gyeonggi-do, 13620
- Recruiting
Research Site
Seoul, 02841
- Recruiting
Research Site
Seoul, 05505
- Recruiting
Research Site
Seoul, 06351
- Recruiting
Research Site
Seoul, 06591
Colombia7 sites, 7 recruiting
- Recruiting
Research Site
Barranquilla, 080020
- Recruiting
Research Site
Bogotá, 111211
- Recruiting
Research Site
Bogotá, 111411
- Recruiting
Research Site
Cali, 760042
- Recruiting
Research Site
Cali, 760046
- Recruiting
Research Site
Floridablanca, 681004
- Recruiting
Research Site
Puerto Colombia, 081007
Argentina5 sites, 5 recruiting
- Recruiting
Research Site
Ciudad Autonoma Buenos Aires, C1430CKE
- Recruiting
Research Site
Córdoba, Córdoba Province, 5000
- Recruiting
Research Site
Córdoba, Córdoba Province, X5003DCE
- Recruiting
Research Site
Ramos Mejía, Buenos Aires, 1704
- Recruiting
Research Site
Rosario, Santa Fe Province, 2000
Georgia5 sites, 5 recruiting
- Recruiting
Research Site
Batumi, 6010
- Recruiting
Research Site
Tbilisi, 0159
- Recruiting
Research Site
Tbilisi, 0160
- Recruiting
Research Site
Tbilisi, 0177
- Recruiting
Research Site
Tbilisi, 0186
Jordan5 sites, 5 recruiting
- Recruiting
Research Site
Amman, 11190
- Recruiting
Research Center
Amman, 11821
- Recruiting
Research Site
Amman, 11942
- Recruiting
Research Center
Irbid, 21166
- Recruiting
Research Center
Irbid, 22110
Hungary4 sites, 4 recruiting
- Recruiting
Research Site
Budapest, 1083
- Recruiting
Research Site
Budapest, 1132
- Recruiting
Research Site
Pécs, 7624
- Recruiting
Research Site
Szeged, 6725
Mexico4 sites, 4 recruiting
- Recruiting
Research Site
Durango, 34000
- Recruiting
Research Site
Guadalajara, Jalisco, 44670
- Recruiting
Research Site
Mexico City, Mexico City, 06700
- Recruiting
Research Site
Querétaro City, Querétaro, 76000
Serbia4 sites, 4 recruiting
- Recruiting
Research Center
Belgrade, 11000
- Recruiting
Research Site
Belgrade, 11000
- Recruiting
Research Site
Pančevo, 26000
- Recruiting
Research Center
Zaječar, 19000
Austria3 sites, 3 recruiting
- Recruiting
Research Site
Graz, 8036
- Recruiting
Research Site
Linz, 4021
- Recruiting
Research Site
Vienna, 1130
Latvia3 sites, 3 recruiting
- Recruiting
Research Site
Riga, 1002
- Recruiting
Research Site
Riga, LV-1079
- Recruiting
Research Site
Tukums, LV-3101
Saudi Arabia3 sites, 3 recruiting
- Recruiting
Research Site
Riyadh, 11211
- Recruiting
Research Site
Riyadh, 11426
- Recruiting
Research Site
Riyadh, 11472
Slovakia3 sites, 3 recruiting
- Recruiting
Research Site
Moldava nad Bodvou, 045 01
- Recruiting
Research Site
Nitra, 950 01
- Recruiting
Research Site
Rožňava, 04801
United Arab Emirates3 sites, 3 recruiting
- Recruiting
Research Site
Abu Dhabi, 133500
- Recruiting
Research Site
Abu Dhabi, 51900
- Recruiting
Research Site
Al Ain City, 15258
United Kingdom3 sites, 3 recruiting
- Recruiting
Research Site
Dundee, Tayside Region, DD1 9SY
- Recruiting
Research Site
London, Greater London, EC1M 6BQ
- Recruiting
Research Site
Torquay, Devon, TQ2 7AA
Belgium2 sites, 2 recruiting
- Recruiting
Research Site
Brussels, 1070
- Recruiting
Research Site
Ghent, 9000
Croatia2 sites, 2 recruiting
- Recruiting
Research Site
Rijeka, 51000
- Recruiting
Research Site
Zagreb, 10000
Lithuania2 sites, 2 recruiting
- Recruiting
Research Site
Kaunas, LT-49387
- Recruiting
Research Site
Kaunas, LT-49449
Singapore2 sites, 2 recruiting
- Recruiting
Research Site
Singapore, 119074
- Recruiting
Research Site
Singapore, 768828
Sweden2 sites, 2 recruiting
- Recruiting
Research Center
Gothenburg, 41345
- Recruiting
Research Center
Stockholm, 14186
About this study
Official title: Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia at High Risk of Acute Pancreatitis (SHASTA-5 Study)
This study will evaluate the efficacy and safety of plozasiran in approximately 288 adult participants with severe hypertriglyceridemia (SHTG) and history of at least two prior acute pancreatitis (AP) events not attributed to other etiologies, with at least one occurring within the last 12 months prior to screening. Eligible participants will be randomly assigned in a double-blind manner to either receive plozasiran 25 mg by subcutaneous (SC) injection every three months (Q3M) or matching placebo. Enrolled participants will be counseled to remain on the specified low-fat diet and background medications throughout the study. Following completion of the double-blind treatment period, or if the participant has a positively adjudicated AP event (whichever occurs first), participants will transition to the 12-month Open-Label Extension (OLE) treatment period receiving plozasiran 25 mg by SC injection Q3M.
- Conditions
- Severe Hypertriglyceridemia
- Being tested
- Plozasiran, Placebo
- Medical subject headings
- Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlozasiranDrug
Also called ARO-APOC3
ARO-APOC3 injection
PlaceboDrug
sterile normal saline (0.9% NaCl)
| Study group | Role | What they receive |
|---|---|---|
| Plozasiran Injection | Experimental | Plozasiran by SC injection every 3 months (Q3M) through completion of the randomized period
Plozasiran by SC injection Q3M through completion of the OLE period Receives: Drug: Plozasiran |
| Placebo | Experimental | calculated volume to match active treatment by SC injection (randomized period) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Occurrence of Positively Adjudicated AP Event (Event Occurring More Than 10 Days After First Dose of Study Drug)
Measured: Randomization up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
Secondary outcomes (8)
Percent Change from Baseline in Fasting Serum Triglyceride (TG) Levels
Measured: Baseline up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)
Proportion of Participants Who Achieve Average Fasting TG Levels of < 880 mg/dL (10 mmol/L)
Measured: From Month 3 up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)
Proportion of Participants Who Achieve Fasting TG Levels of < 500 mg/dL (5.65 mmol/L)
Measured: From Month 3 up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)
Time to First Occurrence of Major Abdominal Pain Event (Event Occurring More Than 10 Days After the First Dose of Study Drug).
Measured: Randomization up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)
Change from Baseline in Patient-Reported Productivity and Activity Impairment as Assessed by the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP) Score
Measured: Baseline up to end of Double Blind Treatment Period Study compared to placebo (Approximate Maximum 50 Months)
Change from Baseline in Patient-Reported Health Status as Assessed by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Score
Measured: Baseline up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) compared to placebo
Measured: From first dose of study drug up to Study Completion (Approximate Maximum 62 Months)
Rate of Occurrence of Adjudicated Major Cardiovascular Events (MACE)
Measured: From first dose of study drug up to Study Completion (Approximate Maximum 62 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2025
- Study start24 Apr 2025
- Primary completionMar 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06880770
- Sponsor's protocol ID
- AROAPOC3-3011
- Acronym
- SHASTA-5
- Status last verified
- Sep 2026
- First submitted
- 12 Mar 2025
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No