Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia (SHASTA-3)

Arrowhead Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Severe Hypertriglyceridemia

Treatments: Drug: Plozasiran Injection; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06347003

AROAPOC3-3003

2023-509300-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 446 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening
• 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 ≤9.0%
• 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 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)

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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446 participants in 2 patient groups, including a placebo group

Plozasiran Injection

Experimental group

Description:

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

Treatment:

Drug: Plozasiran Injection

Placebo

Placebo Comparator group

Description:

calculated volume to match active treatment by sc injection

Treatment:

Drug: Placebo