Clinical trial NCT05185843: A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
Official title: An Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Familial Chylomicronemia Syndrome
Keywords: FCS
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of olezarsen (formerly known as AKCEA -APOCIII-LRX) in participants with FCS previously treated with volanesorsen.

Detailed description: This is a Phase 3, multi-center, open-label safety study in 24 participants with FCS, previously treated with volanesorsen. The study consists of an 8- week screening period, treatment period up to week 209 and a 13-week follow-up period. Participants enrolled will receive olezarsen every 4 weeks during the 209-week Treatment Period.

Treatment period was extended to allow participants to receive olezarsen for an additional 52 weeks for a total of a 209-week treatment period until the drug may be commercially available in the patient's country, or until the Sponsor discontinues the olezarsen development program, whichever occurs earlier.

Eligibility criteria: Key Inclusion Criteria

1. Participants with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801)

   o Study participants in countries where Waylivra® is commercially approved and available for participants should not be deprived of the treatment option with Waylivra®. Participation in this study for such participants will only be allowed when Waylivra® was discontinued due to AEs
2. The following concomitant medications will be allowed if dosing regimen is expected to remain constant through the end of the study (occasional or intermittent use of over-the-counter (OTC) medications will be allowed at Investigator's discretion):

   * Statins, omega-3 fatty acids (prescription and OTC), fibrates, or other lipid-lowering medications. Participants taking OTC omega-3 fatty acids should make every effort to remain on the same brand through the end of the study
   * Antidiabetic medications
   * Oral anticoagulants (e.g., dabigatran, rivaroxaban, or apixaban, and warfarin with regular clinical monitoring)
   * Tamoxifen, estrogens or progestins

Key Exclusion Criteria:

1. Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer
2. Concomitant medication/procedure restrictions:

   1. Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor
   2. Plasma apheresis within 4 weeks prior to Screening or planned during the study

Primary outcomes:
measure: Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)
timeFrame: Baseline to Week 209
measure: Proportion of Participants With Clinical Bleeding Events
timeFrame: Baseline to Week 209
measure: Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50%
timeFrame: Baseline to Week 209
measure: Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g
timeFrame: Baseline to Week 209
measure: Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN)
timeFrame: Baseline to Week 209
measure: Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN
timeFrame: Baseline to Week 209
measure: Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL)
timeFrame: Baseline to Week 209
Secondary outcomes:
measure: Trough (Pre-Dose) Plasma Concentration of Olezarsen
timeFrame: Up to 209 weeks
measure: Post-Treatment Plasma Concentration of Olezarsen
timeFrame: Up to 209 weeks
measure: Change and Percent Change From Baseline in Fasting Triglycerides (TG)
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Chylomicron-TG
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C
timeFrame: Baseline to Week 209
measure: Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)
timeFrame: Baseline to Week 209
measure: Event Rate of Acute Pancreatitis
timeFrame: Up to 209 weeks
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management & Research Center
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)
state: Michigan
city: Rochester
country: United States
facility: University of Rochester School of Medicine
state: New York
city: Vancouver
country: Canada
facility: Centre for Heart Lung Innovation
state: British Columbia
city: Vancouver
country: Canada
facility: ARC Biosystems, Clinical Assessment Unit (CAU)
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universite de Sherbrooke (CHUS)
state: Quebec
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
Study officials:
References: