Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis

Официальное название

Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia at High Risk of Acute Pancreatitis (SHASTA-5 Study)

Обзор

This study will evaluate the efficacy and safety of plozasiran in approximately 288 adult participants with severe hypertriglyceridemia (SHTG) and history of at least two prior acute pancreatitis (AP) events not attributed to other etiologies, with at least one occurring within the last 12 months prior to screening. Eligible participants will be randomly assigned in a double-blind manner to either receive plozasiran 25 mg by subcutaneous (SC) injection every three months (Q3M) or matching placebo. Enrolled participants will be counseled to remain on the specified low-fat diet and background medications throughout the study. Following completion of the double-blind treatment period, or if the participant has a positively adjudicated AP event (whichever occurs first), participants will transition to the 12-month Open-Label Extension (OLE) treatment period receiving plozasiran 25 mg by SC injection Q3M.

Вмешательства

• Препарат Plozasiran
  ARO-APOC3 injection
• Препарат Placebo
  sterile normal saline (0.9% NaCl)

Первичные конечные точки

• Time to First Occurrence of Positively Adjudicated AP Event (Event Occurring More Than 10 Days After First Dose of Study Drug) [Срок оценки: Randomization up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]]

Вторичные конечные точки (8)

• Percent Change from Baseline in Fasting Serum Triglyceride (TG) Levels [Срок оценки: Baseline up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
• Proportion of Participants Who Achieve Average Fasting TG Levels of < 880 mg/dL (10 mmol/L) [Срок оценки: From Month 3 up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
• Proportion of Participants Who Achieve Fasting TG Levels of < 500 mg/dL (5.65 mmol/L) [Срок оценки: From Month 3 up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
• Time to First Occurrence of Major Abdominal Pain Event (Event Occurring More Than 10 Days After the First Dose of Study Drug). [Срок оценки: Randomization up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
• Change from Baseline in Patient-Reported Productivity and Activity Impairment as Assessed by the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP) Score [Срок оценки: Baseline up to end of Double Blind Treatment Period Study compared to placebo (Approximate Maximum 50 Months)]
• Change from Baseline in Patient-Reported Health Status as Assessed by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Score [Срок оценки: Baseline up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)]
• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) compared to placebo [Срок оценки: From first dose of study drug up to Study Completion (Approximate Maximum 62 Months)]
• Rate of Occurrence of Adjudicated Major Cardiovascular Events (MACE) [Срок оценки: From first dose of study drug up to Study Completion (Approximate Maximum 62 Months)]

Критерии участия

Критерии включения

• Males, or nonpregnant (who do not plan to become pregnant) nonlactating females
• Established diagnosis of SHTG and prior documented evidence of fasting TG levels of ≥ 880 mg/dL (≥ 10 mmol/L)
• Documented evidence of at least 1 prior AP event not attributed to other etiologies occurring within the last 60 months prior to Screening.
• Fasting low-density lipoprotein cholesterol (LDL-C) ≤ 130 mg/dL (≤ 3.37 mmol/L) at Screening
• Screening hemoglobin A1c (HbA1c) ≤ 9.5%
• 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, or a treatment failure as determined by the Investigator)

Критерии исключения

• Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1, except inclisiran.
• Use of any other hepatocyte targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5 half-lives lives before day 1. Whichever is longer.
• AP ≤ 4 weeks prior to Randomization/Day 1
• Body mass index (BMI) > 45 kg/m\^2
• Any planned bariatric surgery or similar procedures to induce weight lost starting at consent through End of Study (EOS)
• Planned coronary intervention (e.g. stent placement or heart bypass) during the study
• History of arterial revascularization within 16 weeks of Screening
• History of acute coronary syndrome event within 24 weeks of Screening
• Recent atherosclerotic cardiovascular disease (ASCVD) event within 24 weeks of Screening
• Recent unstable or symptomatic cardiac arrhythmia (including any associated medication changes) within 90 days of Screening. Individuals with stable well-controlled atrial arrhythmia will be allowed to participate in the study
• History of pacemaker or automatic implantable cardioverter defibrillators implant within 30 days before Screening
• New York Heart Association Class III-IV heart failure or last known ejection fraction of < 30%
• Current diagnosis of nephrotic syndrome
• Chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m\^2
• Liver disease defined as cirrhosis or Child-Pugh Class B and C, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5× Upper Limit of Normal (ULN) at Screening

Note: Additional Inclusion/Exclusion Criteria may apply per protocol

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 19 центров

• Research Center — Пекин
• Research Site — Guiyang
• Research Site — Харбин
• Research Site — Luoyang
• Research Site — Luoyang
• Research Site — Zhuzhou
• Research Center — Baotou
• Research Site — Chifeng
• … и ещё 11 центров

США · 16 центров

• Research Site — Los Angeles
• Clinical Research Site 4 — Santa Clarita
• Research Site — New Haven
• Clinical Research Site 6 — Springfield
• Research Site — Indianapolis
• Research Site — Kansas City
• Research Site — Ann Arbor
• Research Site — St Louis
• … и ещё 8 центров

Бразилия · 11 центров

• Research Site — Fortaleza
• Research Site — Belo Horizonte
• Research Site — Belo Horizonte
• Research Site — Belo Horizonte
• Research Site — Curitiba
• Research Site — Porto Alegre
• Research Site — Porto Alegre
• Research Site — Pôrto Alegre
• … и ещё 3 центра

Болгария · 8 центров

• Research Site — Burgas
• Research Site — Pleven
• Research Center — Plovdiv
• Research Site — Plovdiv
• Research Site — Rousse
• Research Site — Sofia
• Research Site — Sofia
• Research Site — Stara Zagora

South Korea · 8 центров

Список центров уточняется — проверьте первичный протокол.

Колумбия · 6 центров

• Research Site — Barranquilla
• Research Site — Bogotá
• Research Site — Bogotá
• Research Site — Cali
• Research Site — Cali
• Research Site — Puerto Colombia

Аргентина · 5 центров

• Research Site — Ramos Mejía
• Research Site — Córdoba
• Research Site — Córdoba
• Research Site — Rosario
• Research Site — Ciudad Autonoma Buenos Aires

Иордания · 5 центров

• Research Site — Amman
• Research Center — Amman
• Research Site — Amman
• Research Center — Irbid
• Research Center — Irbid

Венгрия · 4 центра

• Research Site — Budapest
• Research Site — Budapest
• Research Site — Pécs
• Research Site — Szeged

Сербия · 4 центра

Список центров уточняется — проверьте первичный протокол.

Австрия · 3 центра

• Research Site — Graz
• Research Site — Linz
• Research Site — Vienna

Саудовская Аравия · 3 центра

Список центров уточняется — проверьте первичный протокол.

ОАЭ · 3 центра

Список центров уточняется — проверьте первичный протокол.

Мексика · 2 центра

• Research Site — Guadalajara
• Research Site — Mexico City

Швеция · 2 центра

Список центров уточняется — проверьте первичный протокол.

Oman · 1 центр

• Research Site — Muscat

Сингапур · 1 центр

Список центров уточняется — проверьте первичный протокол.

Великобритания · 1 центр

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06880770 · AROAPOC3-3011

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗