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

Visirna Therapeutics

Status and phase: Completed; Phase 3

Conditions: Familial Chylomicronemia Syndrome

Treatments: Drug: Placebon; Drug: Plozasiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT05902598

U1111-1330-5258 (Registry Identifier)

VSA001-3001

Details and patient eligibility

About

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.

Enrollment: 37 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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:

  1. Newly diagnosed within 12 weeks of screening
  2. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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37 participants in 3 patient groups, including a placebo group

Plozasiran 25 mg

Experimental group

Description:

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

Treatment:

Drug: Plozasiran

Plozasiran 50 mg

Experimental group

Description:

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

Treatment:

Drug: Plozasiran

Placebo

Placebo Comparator group

Description:

Matching placebo administered every 3 months for 12 months

Treatment:

Drug: Placebon