Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis

NCT06880770 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AROAPOC3-3011
• Study Type: interventional
• Target: 288
• Locations: 15 countries
• Sites: 79

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Time to First Occurrence of Positively Adjudicated AP Event (Event Occurring More Than 10 Days After First Dose of Study Drug)

  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

  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)

  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)

  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).

  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

  Baseline up to end of Double Blind Treatment Period Study compared to placebo (Approximate Maximum 50 Months)

Study Arms (2)

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

Drug: Plozasiran

Placebo

EXPERIMENTAL

calculated volume to match active treatment by SC injection (randomized period)

Drug: Placebo

Interventions

Plozasiran DRUG

ARO-APOC3 injection

Also known as: ARO-APOC3

Plozasiran Injection

Placebo DRUG

sterile normal saline (0.9% NaCl)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

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.
• 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
• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (83)

Research Site

Los Angeles, California, 90027, United States

RECRUITING

Clinical Research Site 4

Santa Clarita, California, 91321, United States

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New Haven, Connecticut, 06519, United States

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Clinical Research Site 6

Springfield, Illinois, 62702, United States

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Indianapolis, Indiana, 46202, United States

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Kansas City, Kansas, 66160, United States

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Ann Arbor, Michigan, 48109, United States

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St Louis, Missouri, 63110, United States

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Clinical Research Site 5

North Platte, Nebraska, 69101, United States

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Clinical Research Site 3

Greensboro, North Carolina, 27401, United States

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Wilmington, North Carolina, 28412, United States

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Clinical Research Site 7

Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Clinical Research Site 1

Mesquite, Texas, 75149, United States

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Clinical Research Site 2

San Antonio, Texas, 78233, United States

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Seattle, Washington, 98109, United States

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Ramos Mejía, Buenos Aires, 1704, Argentina

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Córdoba, Córdoba Province, 5000, Argentina

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Córdoba, Córdoba Province, X5003DCE, Argentina

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Rosario, Santa Fe Province, 2000, Argentina

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Ciudad Autonoma Buenos Aires, C1430CKE, Argentina

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Graz, 8036, Austria

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Fortaleza, Ceará, 60430-370, Brazil

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Belo Horizonte, Minas Gerais, 30150-274, Brazil

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Belo Horizonte, Minas Gerais, 30150-320, Brazil

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Belo Horizonte, Minas Gerais, 30220-140, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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Pôrto Alegre, Rio Grande do Sul, 90050-170, Brazil

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São Paulo, São Paulo, 05403-900, Brazil

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Burgas, 8000, Bulgaria

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Pleven, 5800, Bulgaria

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Plovdiv, 4002, Bulgaria

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Plovdiv, 4003, Bulgaria

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Rousse, 7013, Bulgaria

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Sofia, 1404, Bulgaria

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Sofia, 1431, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Beijing, Beijing Municipality, 100730, China

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Guiyang, Guizhou, 550000, China

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Harbin, Heilongjiang, 150040, China

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Baotou, Inner Mongolia, 014010, China

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Chifeng, Inner Mongolia, 024099, China

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Nanchang, Jiangxi, 330006, China

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Shanghai, Shanghai Municipality, 201620, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310000, China

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Hangzhou, Zhejiang, 310003, China

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Beijing, 100053, China

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Nanjing, 210002, China

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Barranquilla, 080020, Colombia

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Cali, 760042, Colombia

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Puerto Colombia, 081007, Colombia

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Budapest, 1083, Hungary

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Budapest, 1132, Hungary

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Szeged, 6725, Hungary

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Amman, 11190, Jordan

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Amman, 11821, Jordan

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Amman, 11942, Jordan

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Irbid, 21166, Jordan

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Irbid, 22110, Jordan

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Guadalajara, Jalisco, 44670, Mexico

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Mexico City, Mexico City, 06700, Mexico

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Muscat, 123, Oman

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Riyadh, 11211, Saudi Arabia

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Riyadh, 11426, Saudi Arabia

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Riyadh, 11472, Saudi Arabia

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Belgrade, 11000, Serbia

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Belgrade, 11000, Serbia

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Pančevo, 26000, Serbia

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Zaječar, 19000, Serbia

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Seongnam-si, Gyeonggi-do, 13620, South Korea

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Jeonju, Jeollabuk-do, 54907, South Korea

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Busan, 49201, South Korea

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Sejong, 30099, South Korea

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Seoul, 02841, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Gothenburg, 41345, Sweden

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Stockholm, 14186, Sweden

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Abu Dhabi, 133500, United Arab Emirates

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Abu Dhabi, 51900, United Arab Emirates

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Al Ain City, 15258, United Arab Emirates

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MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

plozasiran

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Medical Monitor

CONTACT

626-304-3400; plozasiran@arrowheadpharma.com

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 12, 2025
• First Posted: March 18, 2025
• Study Start: April 24, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2); SA (3); AR (5); CO (3); HU (3); BR (7); US (16); SE (2); OM (1); AE (3); BU (8); AU (1); JO (5); KR (8); CN (12)