Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia

Severe Hypertriglyceridemia Clinical Trial

— SHASTA-3  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06347003
• Other study ID #: AROAPOC3-3003
• Secondary ID: 2023-509300-14
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: October 2026

Study information

• Verified date: May 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: 405
• 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 (=5.65mmol/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%

• Willing to follow diet counseling and maintain a stable low-fat diet

• 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

• 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

• Acute pancreatitis within 4 weeks prior to screening

• 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	CHEAR Center LLC	Bronx	New York
United States	Legacy Clinical Trials	Colorado Springs	Colorado
United States	Elite Clinical Research Center	Flint	Michigan
United States	National Institute of Clinical Research	Garden Grove	California
United States	Jefferson City Medical Group	Jefferson City	Missouri
United States	Santa Rosa Medical Centers of Nevada	Las Vegas	Nevada
United States	Endocrine Associates of West Village	Long Island City	New York
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Lynn Institute of Norman	Norman	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Midwest Regional Health Services LLC	Omaha	Nebraska
United States	Florida Institute for Clinical Research	Orlando	Florida
United States	Velocity Clinical Research, Panorama City	Panorama City	California
United States	Cardiovascular Research Center of Knoxville	Powell	Tennessee
United States	Meridian Clinical Research	Savannah	Georgia

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 Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 Compared to Placebo		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 Participants Who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo		Month 10, Month 12
Secondary	Number of Participants 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) 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	Incidence Rates of 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 Participants 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 Participants Receiving Plozasiran Over Time Through Month 12		From first dose of study drug through Month 12