Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS)

Familial Chylomicronemia Clinical Trial

— PALISADE  

Official title:

A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05089084
• Other study ID #: AROAPOC3-3001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 11, 2022
• Est. completion date: April 2026

Study information

• Verified date: April 2024
• Source: Arrowhead Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 plozasiran) in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of plozasiran or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive plozasiran.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: April 2026
• Est. primary completion date: April 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Fasting TG = 10 mmol/L (= 880 mg/dL) at screening refractory to standard lipid lowering therapy
• Diagnosis of FCS
• Willing to follow dietary counseling as per investigator judgement based on local standard of care
• Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
• Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
• Women of childbearing potential on hormonal contraceptives must be stable on the medication for = 2 menstrual cycles prior to Day 1

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 newly diagnosed within 12 weeks of Screening or where 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
• History of major surgery within 12 weeks of Day 1
• Uncontrolled hypertension
• On treatment with human immunodeficiency virus (HIV) antiretroviral therapy
• Seropositive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• New York Heart Association (NYHA) Clas II, III, or IV heart failure Note: Additional Inclusion/Exclusion criteria may apply per protocol

Related Conditions & MeSH terms

• Familial Chylomicronemia
• Hyperlipoproteinemia Type I

Intervention

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

Locations

Country	Name	City	State
Argentina	Instituto Medico DAMIC	Córdoba
Argentina	Instituto Modelo de Gastroenterologia	Formosa
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Austin Health	Melbourne
Australia	Baker Heart and Diabetes Institute	Melbourne	Victoria
Australia	Linear Clinical Research Ltd	Nedlands
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Austria	Medizinische Universitaet Graz	Graz
Belgium	Universitair Ziekenhuis Antwerpen (UZA)	Edegem
Belgium	University Hospital Ghent	Ghent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Belgium	Centre Hospitalier Universitaire (CHU) de Liege	Liège
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Robarts Research Institute	London	Ontario
Canada	Institute de Recherches Cliniques de Montreal	Montreal	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Québec	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Croatia	University Hospital Center Zagreb -Rebro, Department for Metabolic Diseases	Zagreb
France	AP-HM-Hopital de La Conception	Marseille	Cedez 05
France	AP-HP Hopital Pitie-Salpetriere	Paris
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitaetsklinikum Leipzig	Leipzig
Ireland	University Hospital Galway	Galway
Israel	Hadassah Medical Center Ein Karem	Jerusalem
Japan	Chiba University Hospital	Chiba
Japan	Kanazawa University Hospital	Ishikawa
Japan	Rinku General Medical Center	Osaka
Japan	Jichi Medical University Hospital	Tochigi
Japan	Nippon Medical School Hospital	Tokyo
Japan	Tokyo University Hospital	Tokyo
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Instituto de Diabetes Obesidad y Nutrición S.C.	Cuernavaca	Morelos,
Mexico	Centro Especializado en Diabetes Obesidad y Prevención de entermedades Cardiovasculares (CEDOPEC)	Mexico City
Mexico	National Institute of Medical Sciences and Nutrition - Salvador Zubiran (INCMNSZ)	Tlalpan	Mexico DF
New Zealand	Middlemore Clinical Trials	Auckland
New Zealand	NZCR OPCO Ltd	Auckland
New Zealand	New Zealand Clinical Research	Christchurch
Oman	Sultan Qaboos University Hospital	Muscat
Poland	Instytut Centrum Zdrowia Matki Polki	Lódz
Serbia	Clinical Center of Serbia, Institute of Endocrinology, Diabetes and Metabolic Diseases	Belgrade
Serbia	Clinical Centre Nis	Niš
Singapore	National University Hospital	Singapore
Spain	Hospital Abente y Lago	A Coruña
Spain	Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Clinico Universitario de Santiago	Santiago De Compostela
Turkey	Ege University Hospital Department Of Infectious Diseases	Izmir
Turkey	Erciyes University Faculty of Medicine	Melikgazi	Kayseri
United States	Texas Diabetes and Endocrinology	Austin	Texas
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	Centennial Medical Group	Elkridge	Maryland
United States	Ascension St. Vincent Cardiovascular Research Institute	Indianapolis	Indiana
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	York Clinical Research, LLC	Norfolk	Virginia
United States	Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research	Saint Louis	Missouri
United States	Herman Clinical Research, LLC	Suwanee	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Croatia,  France,  Germany,  Ireland,  Israel,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Oman,  Poland,  Serbia,  Singapore,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Fasting Triglycerides (TG) at Month 10		Baseline, Month 10
Secondary	Percent Change from Baseline in Fasting TG at Month 10 and Month 12 (Averaged)		Baseline, Month 10, Month 12
Secondary	Percent Change from Baseline in Apolipoprotein C-III (APOC3) at Month 10		Baseline, Month 10
Secondary	Percent Change from Baseline in Fasting APOC3 at Month 12		Baseline, Month 12
Secondary	Percent Change from Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10		Baseline, Month 10
Secondary	Percent Change from Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10		Baseline, Month 10
Secondary	Percent Change from Baseline in Fasting TG at Month 12		Baseline, Month 12
Secondary	Percent Change from Baseline in Fasting Non-HDL-C at Month 12		Baseline, Month 12
Secondary	Percent Change from Baseline in Fasting HDL-C at Month 12		Baseline, Month 12
Secondary	Proportion of Patients Achieving TG of < 500 mg/dL at Month 10		Month 10
Secondary	Proportion of Patients Achieving TG of < 500 mg/dL at Month 12		Month 12
Secondary	Change from Baseline in Fasting TG Over Time		Baseline, up through Month 12
Secondary	Percent Change from Baseline in Fasting TG Over Time		Baseline, up through Month 12
Secondary	Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs)		From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period)
Secondary	Number of Participants with Positively Adjudicated Events of Acute Pancreatitis		From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period)