Study of Plozasiran in Adults With Severe Hypertriglyceridemia

NCT06347016 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: AROAPOC3-30042023-509301-80
• Study Type: interventional
• Target: 311
• Locations: 16 countries
• Sites: 149

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.

Conditions

Severe Hypertriglyceridemia

Outcome Measures

Primary Outcomes (1)

• Percent change in fasting serum TG levels from baseline to Month 12 compared to placebo

  Baseline, Month 12

Secondary Outcomes (19)

• Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo

  Baseline, Month 10

• Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 compared to placebo

  Baseline, Month 12

• Proportion of Subjects 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

Study Arms (2)

Plozasiran Injection

EXPERIMENTAL

4 doses of plozasiran (ARO-APOC3) by subcutaneous (sc) injection

Drug: Plozasiran Injection

Placebo

PLACEBO COMPARATOR

calculated volume to match active treatment by sc injection

Drug: Placebo

Interventions

Plozasiran Injection 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:

• Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/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%
• Must be on standard of care lipid-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 (except inclisiran, which is permitted)
• 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
• Body mass index \>45kg/m\^2

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (149)

Research Site 1

Birmingham, Alabama, 35205, United States

Location

Research Site 2

Mobile, Alabama, 36604, United States

Location

Research Site 3

Beverly Hills, California, 90211, United States

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Research Site 4

Canoga Park, California, 91303, United States

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Research Site 5

Huntington Beach, California, 92648, United States

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Research Site 6

Lincoln, California, 95648, United States

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Research Site 7

Long Beach, California, 90822, United States

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Research Site 8

Oxnard, California, 93030, United States

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Research Site 9

Clearwater, Florida, 33756, United States

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Research Site 10

North Miami, Florida, 33162, United States

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Research Site 11

Sarasota, Florida, 34239, United States

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Research Site 12

Lawrenceville, Georgia, 30044, United States

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Research Site 13

Sugar Hill, Georgia, 30518, United States

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Research Site 14

Elkhart, Indiana, 46514, United States

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Research Site 15

Indianapolis, Indiana, 46290, United States

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Research Site 16

South Bend, Indiana, 46617, United States

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Research Site 17

Overland Park, Kansas, 66211, United States

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Research Site 18

Topeka, Kansas, 66606, United States

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Research Site 19

Metairie, Louisiana, 70001, United States

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Research Site 20

Annapolis, Maryland, 21401, United States

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Research Site 21

Jackson, Mississippi, 39202, United States

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Research Site 22

Fremont, Nebraska, 68025, United States

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Research Site 23

Norfolk, Nebraska, 68701, United States

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Research Site 24

Morristown, New Jersey, 07960, United States

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Research Site 26

New York, New York, 10029, United States

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Research Site 27

Riverhead, New York, 11901, United States

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Research Site 25

The Bronx, New York, 10461, United States

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Research Site 28

Asheboro, North Carolina, 27203, United States

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Research Site 29

Wilmington, North Carolina, 28412, United States

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Research Site 30

Beavercreek, Ohio, 45431, United States

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Research Site 31

Columbus, Ohio, 43214, United States

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Research Site 32

Oklahoma City, Oklahoma, 73112, United States

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Research Site 33

Horsham, Pennsylvania, 19044, United States

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Research Site 34

Newport, Pennsylvania, 17074, United States

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Research Site 35

Philadelphia, Pennsylvania, 19104, United States

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Research Site 36

Philadelphia, Pennsylvania, 19104, United States

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Research Site 37

Fort Mill, South Carolina, 29707, United States

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Research Site 38

Greenville, South Carolina, 29607, United States

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Research Site 39

Chattanooga, Tennessee, 37411, United States

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Research Site 40

Fort Worth, Texas, 76132, United States

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Research Site 41

Houston, Texas, 77040, United States

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Research Site 42

Houston, Texas, 77090, United States

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Research Site 43

Houston, Texas, 77090, United States

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Research Site 44

Sugar Land, Texas, 77479, United States

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Research Site 45

Tomball, Texas, 77375, United States

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Research Site 46

Victoria, Texas, 77901, United States

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Research Site 47

Bountiful, Utah, 84010, United States

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Research Site 48

St. George, Utah, 84790, United States

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Research Site 49

Manassas, Virginia, 20110, United States

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Research Site 50

Roanoke, Virginia, 24014, United States

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Research Site 52

CABA, Buenos Aires, 1128, Argentina

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Research Site 51

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1056ABJ, Argentina

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Research Site 54

Córdoba, Córdoba Province, 5003, Argentina

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Research Site 53

Godoy Cruz, Mendoza Province, 5501, Argentina

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Research Site 55

Rosario, Santa Fe Province, 2000, Argentina

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Research Site 61

Salvador, Estado de Bahia, 40170, Brazil

Location

Research Site 56

Brasília, Federal District, 70710, Brazil

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Research Site 59

Belo Horizonte, Minas Gerais, 30150, Brazil

Location

Research Site 62

Aracaju, Sergipe, 49055-530, Brazil

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Research Site 57

Campinas, São Paulo, 13060, Brazil

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Research Site 58

Santo André, São Paulo, 09080, Brazil

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Research Site 60

São José do Rio Preto, São Paulo, 15090, Brazil

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Research Site 63

Recife, 52051-380, Brazil

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Research Site 64

Byala, 7100, Bulgaria

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Research Site 65

Dimitrovgrad, 6400, Bulgaria

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Research Site 66

Haskovo, 6300, Bulgaria

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Research Site 67

Kyustendil, 2500, Bulgaria

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Research Site 68

Rousse, 7013, Bulgaria

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Research Site 69

Sevlievo, 5400, Bulgaria

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Research Site 76

Sofia, 1202, Bulgaria

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Research Site 70

Sofia, 1431, Bulgaria

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Research Site 73

Sofia, 1431, Bulgaria

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Research Site 71

Sofia, 1510, Bulgaria

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Research Site 75

Sofia, 1616, Bulgaria

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Research Site 72

Sofia, 1680, Bulgaria

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Research Site 74

Sofia, 1750, Bulgaria

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Research Site 77

Stara Zagora, 6003, Bulgaria

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Research Site 78

North Vancouver, British Columbia, V7M 2H4, Canada

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Research Site 79

Chicoutimi, Quebec, G7H 7K9, Canada

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Research Site 80

Laval, Quebec, H7T 2P5, Canada

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Research Site 81

Québec, Quebec, G1G 3Y8, Canada

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Research Site 82

Terrebonne, Quebec, J6V2H2, Canada

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Research Site 83

Brno, 65691, Czechia

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Research Site 84

Náchod, 547 01, Czechia

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Research Site 85

Olomouc, 77900, Czechia

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Research Site 86

Prague, 100 00, Czechia

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Research Site 88

Slaný, 15006, Czechia

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Research Site 89

Teplice, 41501, Czechia

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Research Site 87

Trutnov, 541 01, Czechia

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Research Site 91

Marseille, Bouches-du-Rhône, 13005, France

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Research Site 92

Pessac, Gironde, 33604, France

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Research Site 93

Bayonne, Pyrenees Atlantiques, 64100, France

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Research Site 94

Lyon, Rhone, 69007, France

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Research Site 90

Paris, 75013, France

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Research Site 95

Deggingen, Baden-Wurttemberg, 73326, Germany

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Research Site 96

Wallerfing, Bavaria, 94574, Germany

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Research Site 97

Magdeburg, Saxony-Anhalt, Germany

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Research Site 98

Berlin, State of Berlin, 13353, Germany

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Research Site 99

Békéscsaba, 5600, Hungary

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Research Site 100

Kaposvár, 7400, Hungary

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Research Site 101

Miskolc, 3530, Hungary

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Research Site 102

Pécs, 7623, Hungary

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Research Site 104

Pécs, 7635, Hungary

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Research Site 103

Zalaegerszeg, 8900, Hungary

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Research Site 107

Daugavpils, LV-5410, Latvia

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Research Site 105

Daugavpils, LV-5417, Latvia

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Research Site 106

Daugavpils, LV-5417, Latvia

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Research Site 108

Kuldīga, LV-3301, Latvia

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Research Site 109

Riga, LV-1002, Latvia

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Research Site 110

Riga, LV-1038, Latvia

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Research Site 111

Riga, LV-1050, Latvia

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Research Site 112

Tukums, LV-3101, Latvia

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Research Site 115

Kaunas, LT-48259, Lithuania

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Research Site 113

Kaunas, LT-49387, Lithuania

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Research Site 114

Kaunas, LT-50177, Lithuania

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Research Site 118

Šiauliai, LT-76206, Lithuania

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Research Site 116

Vilnius, LT-08406, Lithuania

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Research Site 117

Vilnius, LT-08406, Lithuania

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Research Site 119

Christchurch, 8011, New Zealand

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Research Site 120

New Plymouth, 4310, New Zealand

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Research Site 121

Newtown, 6021, New Zealand

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Research Site 122

Bydgoszcz, 85-065, Poland

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Research Site 123

Gdynia, 81-338, Poland

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Research Site 124

Katowice, 40-156, Poland

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Research Site 129

Lodz, 94-255, Poland

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Research Site 125

Malbork, 82-200, Poland

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Research Site 126

Szczecin, 71-500, Poland

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Research Site 130

Torun, 87-100, Poland

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Research Site 127

Wroclaw, 51-314, Poland

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Research Site 128

Zamość, 22-400, Poland

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Research Site 134

Bratislava, 83101, Slovakia

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Research Site 131

Nové Zámky, 94002, Slovakia

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Research Site 132

Prešov, 08001, Slovakia

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Research Site 133

Rožňava, 04801, Slovakia

Location

Research Site 135

Centurion, Gauteng, 0157, South Africa

Location

Research Site 136

Krugersdorp, Gauteng, 1739, South Africa

Location

Research Site 137

Pretoria, Gauteng, 0184, South Africa

Location

Research Site 138

Durban, KwaZulu-Natal, 4449, South Africa

Location

Research Site 144

Cape Town, Western Cape, 7441, South Africa

Location

Research Site 139

Cape Town, Western Cape, 7500, South Africa

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Research Site 140

Cape Town, Western Cape, 7500, South Africa

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Research Site 143

Cape Town, Western Cape, 7530, South Africa

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Research Site 145

Cape Town, Western Cape, 7925, South Africa

Location

Research Site 146

Mossel Bay, Western Cape, 6500, South Africa

Location

Research Site 142

Plettenberg Bay, Western Cape, 6600, South Africa

Location

Research Site 141

Somerset West, Western Cape, 7570, South Africa

Location

Research Site 149

A Coruña, La Coruña, 15006, Spain

Location

Research Site 147

Madrid, 28041, Spain

Location

Research Site 148

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

plozasiran

Condition Hierarchy (Ancestors)

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

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 23, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 24, 2025

Record last verified: 2025-10

Locations

LA (8); LI (6); PL (9); SL (4); DE (4); CA (5); US (50); AR (5); ES (3); ZA (12); BU (14); BR (8); FR (5); CZ (7); HU (6); NZ (3)