A Phase 3 Study of ARO-APOC3 / VSA001 / SAR449124 (Plozasiran) in Chinese Adults With Familial Chylomicronemia Syndrome

NCT05902598 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: VSA001-3001U1111-1330-5258
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blinded, placebo controlled, two periods phase 3 clinical study. The primary objective of the study was to evaluate the efficacy and safety of Plozasiran injection in Chinese adults with familial chylomicronemia syndrome (FCS). A total of 37 participants were enrolled in the study. The duration of the study randomized period was approximately 112 weeks, including a screening period of up to 8 weeks and a treatment period of up to 104 weeks. Participants who completed the randomized period will continue in a 1-year open-label extension period where all participants will receive Plozasiran.

Conditions

Familial Chylomicronemia Syndrome

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Fasting Serum Triglyceride (TG) at Month 10

  Blood samples for lipid parameters were collected at the specified time points. Fasting serum TG at Month 10 was defined as geometric mean of 2 measurements taken during Month 10, or the other non-missing measurement if any one of the two measurements was missing during Month 10. Analysis was performed on the basis of the handling strategy for intercurrent events, missing fasting serum was imputed mainly based on the Pattern Mixture Models (PMM). Descriptive statistics were calculated based on non-imputed data.

  Baseline to Month 10

Secondary Outcomes (10)

• Percent Change From Baseline in Fasting Serum TG at Months 10 and 12 (Averaged)

  Baseline to Months 10 and 12 (averaged)

• Percent Change From Baseline in Fasting Serum Apolipoprotein C3 (APOC3) at Month 10

  Baseline to Month 10

• Percent Change From Baseline in Fasting Serum APOC3 at Month 12

  Baseline to Month 12

• Percent Change From Baseline in Fasting Serum Non-high Density Lipoprotein Cholesterol (Non-HDL-C) and High Density Lipoprotein Cholesterol (HDL-C) at Month 10

  Baseline to Month 10

• Percent Change From Baseline in Fasting Serum TG, Non-HDL-C, and HDL-C at Month 12

  Baseline to Month 12

Study Arms (3)

Plozasiran 25 mg

EXPERIMENTAL

Plozasiran 25 mg administered every 3 months for 12 months (randomized period), followed by an open-label period of 12 months

Drug: Plozasiran

Plozasiran 50 mg

EXPERIMENTAL

Plozasiran 50 mg administered every 3 months for 12 months (randomized period), followed by an open-label period of 12 months

Drug: Plozasiran

Placebo

PLACEBO COMPARATOR

Matching placebo administered every 3 months for 12 months

Drug: Placebon

Interventions

Plozasiran DRUG

Subcutaneous injection

Also known as: ARO-APOC3, SAR449124, VSA001

Plozasiran 25 mg; Plozasiran 50 mg

Placebon DRUG

Subcutaneous injection

Also known as: Normal saline

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 ≥18 years of age
• Fasting triglycerides (TG) ≥10 mmol/L (\~880 mg/dL) at screening, that is refractory to standard lipid lowering therapy (sample drawn after at least the minimum time on stable lipid-lowering regimen described in protocol). Two repeat tests are allowed to qualify.
• A diagnosis of FCS
• Willing to follow dietary counseling as per PI judgment based on local standard of care, consistent with an intake of ≤20 g of fat per day during the study
• If on medications for management of type 2 diabetes, or other medications specified in protocol, the dosing regimen must be stable before collection of qualified lipid parameter at screening.
• Participants with a medical history of clinical atherosclerotic cardiovascular disease (ASCVD) or those with elevated 10-year ASCVD risk (eg, ≥7.5% per American Heart Association / American College of Cardiology risk calculator) must be on appropriate lipid-lowering therapy as per local standard of care (ie, including moderate to high intensity statin, as indicated) prior to collection of qualifying TG levels.
• Participants of childbearing potential must agree to use a highly effective form of contraception in addition to a male condom, during the study and for at least 24 weeks after the last dose of investigational product (IP). Women of childbearing potential on a hormonal contraceptive must be stable on the medication for ≥1 menstrual cycles prior to Day 1. Men must not donate sperm during the study and for at least 24 weeks after the last dose of IP.

You may not qualify if:

• Current use or use within the last 365 days from Day 1 of any hepatocyte-targeted siRNA or antisense oligonucleotide molecule
• Diabetes mellitus with any of the following:
• Newly diagnosed within 12 weeks of screening
• HbA1c ≥9.0% at screening
• Active pancreatitis within 12 weeks before Day 1
• History of acute coronary syndrome event within 24 weeks of Day 1
• The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: collaborator
• Visirna Therapeutics HK Limited: lead

Study Sites (1)

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome

Interventions

plozasiran; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext 6#

Study Officials

• Dong YOU, MD., PhD.

  Visirna Therapeutics HK Limited

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: May 31, 2023
• First Posted: June 15, 2023
• Study Start: July 10, 2023
• Primary Completion: November 26, 2024
• Study Completion: January 9, 2026
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)