Study of Plozasiran in Adults With Severe Hypertriglyceridemia

Severe Hypertriglyceridemia Clinical Trial

— SHASTA-4  

Official title:

Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozsiran in Adults With Severe Hypertriglyceridemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06347016
• Other study ID #: AROAPOC3-3004
• Secondary ID: 2023-509301-80
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: October 2026

Study information

• Verified date: June 2024
• Source: Arrowhead Pharmaceuticals
• Contact: Medical Monitor
• Phone: 626-304-3400
• Email: plozasiran[@]arrowheadpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: October 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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 =8.5%

• Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Exclusion Criteria:

• 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

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Related Conditions & MeSH terms

• Hypertriglyceridemia
• Severe Hypertriglyceridemia

Intervention

Drug:
• Plozasiran Injection
ARO-APOC3 Injection
• Placebo
sterile normal saline (0.9% NaCl)

Locations

Country	Name	City	State
United States	Annapolis Internal Medicine	Annapolis	Maryland
United States	National Heart Institute	Beverly Hills	California
United States	Cope Family Medicine	Bountiful	Utah
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	Diabetes and Thyroid Center of Fort Worth	Fort Worth	Texas
United States	Tribe Clinical Research	Greenville	South Carolina
United States	Care and Cure Clinic	Houston	Texas
United States	Juno Research LLC	Houston	Texas
United States	Spring Clinical Research	Houston	Texas
United States	Velocity Clinical Research	Norfolk	Nebraska
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	The South Bend Clinic LLC	South Bend	Indiana
United States	Cotton-O'Neil Clinical Research Center, Stormont-Vail West	Topeka	Kansas
United States	Crossroads Clinical Research	Victoria	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo		Baseline, Month 12
Secondary	Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo		Baseline, Month 10
Secondary	Proportion of Subjects Who Achieve Fasting TG Levels of < 500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12		Month 10, Month 12
Secondary	Adjudicated Abdominal Clinical Event Rate (Including Emergency Room Visits or Hospitalizations for Abdominal Pain Attributed to Hypertriglyceridemia and Events of Documented Pancreatitis) During the Treatment Period Compared to Placebo at Month 12		Month 12
Secondary	Proportion of Subjects Who Achieve Fasting TG Levels of <150mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo		Month 10, Month 12
Secondary	Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo		From first dose of study drug through Month 12
Secondary	Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment		From first dose of study drug through Month 12
Secondary	Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment		From first dose of study drug through Month 12
Secondary	Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment		From first dose of study drug through Month 12
Secondary	Change from Baseline in Hemoglobin A1c (HbA1c) and Other Glycemic Control Parameters During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Change from Baseline in C-Peptide During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Change from Baseline in Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Initiation of New Medication for Hyperglycemia among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo		From first dose of study drug through Month 12
Secondary	Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12		From first dose of study drug through Month 12
Secondary	Titers of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12		From first dose of study drug through Month 12