Familial Chylomicronemia Syndrome
Conditions
Keywords
FCS
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.
Interventions
DRUGOlezarsen
Olezarsen will be administered by SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3) | Baseline to Week 209 |
| Proportion of Participants With Clinical Bleeding Events | Baseline to Week 209 |
| Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50% | Baseline to Week 209 |
| Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g | Baseline to Week 209 |
| Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN) | Baseline to Week 209 |
| Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN | Baseline to Week 209 |
| Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL) | Baseline to Week 209 |
Secondary
| Measure | Time frame |
|---|---|
| Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Apoprotein B (apoB) | Baseline to Week 209 |
| Trough (Pre-Dose) Plasma Concentration of Olezarsen | Up to 209 weeks |
| Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1) | Baseline to Week 209 |
| Event Rate of Acute Pancreatitis | Up to 209 weeks |
| Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48) | Baseline to Week 209 |
| Post-Treatment Plasma Concentration of Olezarsen | Up to 209 weeks |
| Change and Percent Change From Baseline in Fasting Triglycerides (TG) | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III) | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Chylomicron-TG | Baseline to Week 209 |
| Change and Percent Change From Baseline in Fasting Total Cholesterol (TC) | Baseline to Week 209 |
Countries
Canada, Sweden, United States
Outcome results
None listed