Study to Evaluate Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-4 Study)

Phase 3

Active, not recruiting

Conditions: Severe hypertriglyceridemia (SHTG)

Registration Number: 2023-509301-80-00

Lead Sponsor: Arrowhead Pharmaceuticals Inc.

Brief Summary: To demonstrate the efficacy of plozasiran on reducing fasting serum TG levels

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 149

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 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 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

Subjects 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 a previous adverse reaction associated with, attributed to, or caused by specific drug) prior to collection of qualifying TG levels.)

Exclusion Criteria

Use of any hepatocyte-targeted 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 PK, whichever is longer.

Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 hyperlipoproteinemia) by documentation of confirmed homozygote, compound heterozygote or double heterozygote for loss-of-function mutations in type 1-causing genes

Acute pancreatitis within 4 weeks prior to screening (S1).

Body mass index >45 kg/m2

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo		Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo

Secondary Outcome Measures

Name	Time	Method
Percent change in fasting serum TG levels from baseline to Month 10 (V8 and V9) compared to placebo		Percent change in fasting serum TG levels from baseline to Month 10 (V8 and V9) compared to placebo
Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 (V10 and V11) compared to placebo		Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 (V10 and V11) compared to placebo
Proportion of subjects who achieve fasting TG levels of <150 mg/dL (<1.69 mmol/L) at Month 12 (V10 and V11) compared to placebo		Proportion of subjects who achieve fasting TG levels of <150 mg/dL (<1.69 mmol/L) at Month 12 (V10 and V11) compared to placebo
Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 (V11) compared to placebo		Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 (V11) compared to placebo
Percent change in non-HDL-C from baseline to Month 12 (V11) compared to placebo		Percent change in non-HDL-C from baseline to Month 12 (V11) compared to placebo
Adjudicated abdominal clinical event rate including ER visits or hospitalizations for abdominal pain attributed to hypertriglyceridemia and events of documented pancreatitis during the treatment period compared to placebo at Month 12 (V11)		Adjudicated abdominal clinical event rate including ER visits or hospitalizations for abdominal pain attributed to hypertriglyceridemia and events of documented pancreatitis during the treatment period compared to placebo at Month 12 (V11)

Trial Locations

Locations (70): Inmedica UAB
🇱🇹
Kaunas, Lithuania
Saules seimos medicinos centras UAB
🇱🇹
Kaunas, Lithuania
Vilniaus Universiteto Ligonine Santaros Klinikos Vsi
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Vilnius, Lithuania
Kaunas City Polyclinic, Public Institution
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Kaunas, Lithuania
Klinikiniai Sprendimai UAB
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Kovno, Lithuania
Pirmoji Viltis UAB
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Siauliai, Lithuania
Da Vinci Spa Kft.
🇭🇺
Pecs, Hungary
Obudai Egeszseguegyi Centrum Kft.
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Kaposvar, Hungary
Coromed-Smo Kft.
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Pecs, Hungary
Nyiro Gyula Orszagos Pszichiatriai es Addiktologiai Intezet
🇭🇺
Budapest, Hungary
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Inmedica UAB
🇱🇹Kaunas, Lithuania
Jolanta Elena Marcinkeviciene
Site contact
+37068651359
jolantamar@yahoo.com