Clinical trial NCT05089084: Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS)
Official title: A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Familial Chylomicronemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-22
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change from Baseline in Fasting Triglycerides (TG) at Month 10
timeFrame: Baseline, Month 10
Secondary outcomes:
measure: Percent Change from Baseline in Fasting TG at Month 10 and Month 12 (Averaged)
timeFrame: Baseline, Month 10, Month 12
measure: Percent Change from Baseline in Apolipoprotein C-III (APOC3) at Month 10
timeFrame: Baseline, Month 10
measure: Percent Change from Baseline in Fasting APOC3 at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change from Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10
timeFrame: Baseline, Month 10
measure: Percent Change from Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10
timeFrame: Baseline, Month 10
measure: Percent Change from Baseline in Fasting TG at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change from Baseline in Fasting Non-HDL-C at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change from Baseline in Fasting HDL-C at Month 12
timeFrame: Baseline, Month 12
measure: Proportion of Patients Achieving TG of < 500 mg/dL at Month 10
timeFrame: Month 10
measure: Proportion of Patients Achieving TG of < 500 mg/dL at Month 12
timeFrame: Month 12
measure: Change from Baseline in Fasting TG Over Time
timeFrame: Baseline, up through Month 12
measure: Percent Change from Baseline in Fasting TG Over Time
timeFrame: Baseline, up through Month 12
measure: Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period)
measure: Number of Participants with Positively Adjudicated Events of Acute Pancreatitis
timeFrame: From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period)
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Suwanee
country: United States
facility: Herman Clinical Research, LLC
state: Georgia
city: Indianapolis
country: United States
facility: Ascension St. Vincent Cardiovascular Research Institute
state: Indiana
city: Elkridge
country: United States
facility: Centennial Medical Group
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
state: Missouri
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: Austin
country: United States
facility: Texas Diabetes and Endocrinology
state: Texas
city: Norfolk
country: United States
facility: York Clinical Research, LLC
state: Virginia
city: Córdoba
country: Argentina
facility: Instituto Medico DAMIC
city: Formosa
country: Argentina
facility: Instituto Modelo de Gastroenterologia
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Baker Heart and Diabetes Institute
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA)
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) de Liege
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Institute de Recherches Cliniques de Montreal
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
state: Quebec
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb -Rebro, Department for Metabolic Diseases
city: Marseille
country: France
facility: AP-HM-Hopital de La Conception
state: Cedez 05
city: Paris
country: France
facility: AP-HP Hopital Pitie-Salpetriere
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Galway
country: Ireland
facility: University Hospital Galway
city: Jerusalem
country: Israel
facility: Hadassah Medical Center Ein Karem
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Ishikawa
country: Japan
facility: Kanazawa University Hospital
city: Osaka
country: Japan
facility: Rinku General Medical Center
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital
city: Tokyo
country: Japan
facility: Tokyo University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Tlalpan
country: Mexico
facility: National Institute of Medical Sciences and Nutrition - Salvador Zubiran (INCMNSZ)
state: Mexico DF
city: Cuernavaca
country: Mexico
facility: Instituto de Diabetes Obesidad y Nutrición S.C.
state: Morelos,
city: Mexico City
country: Mexico
facility: Centro Especializado en Diabetes Obesidad y Prevención de entermedades Cardiovasculares (CEDOPEC)
city: Auckland
country: New Zealand
facility: NZCR OPCO Ltd
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Institute of Endocrinology, Diabetes and Metabolic Diseases
city: Niš
country: Serbia
facility: Clinical Centre Nis
city: Singapore
country: Singapore
facility: National University Hospital
city: A Coruña
country: Spain
facility: Hospital Abente y Lago
city: Granada
country: Spain
facility: Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Melikgazi
country: Turkey
facility: Erciyes University Faculty of Medicine
state: Kayseri
city: İzmir
country: Turkey
facility: Ege University Hospital Department Of Infectious Diseases
Study officials:
References: