Homozygous Familial Hypercholesterolemia
Conditions
Keywords
Hyperlipoproteinemia Type II, Lipid Metabolism, Inborn Errors, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Congenital, Hereditary, and Neonatal Diseases and Abnormalities, Hyperlipoproteinemias, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases, Nutritional and Metabolic Diseases, Homozygous Familial Hypercholesterolemia, Zodasiran
Brief summary
This study will evaluate the efficacy and safety of zodasiran subcutaneous (sc) injection in participants 12 to \<18 years of age with genetically or clinically diagnosed homozygous familial hypercholesterolemia (HoFH) and low-density lipoprotein cholesterol (LDL-C) ≥116 milligrams per deciliter (mg/dL) on maximally tolerated lipid-lowering therapy.
Interventions
DRUGZodasiran
By sc injection
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Adolescents 12 to \<18 years of age who are nonpregnant, nonlactating, and do not plan to become pregnant during the study * Body weight ≥35 kilograms (kg) at screening * HoFH based on a supportive genetic test (from a source-verifiable medical record or based on screening genotype) or clinical diagnosis * Screening LDL-C ≥116 mg/dL (3 mmol/L) * Screening hemoglobin A1c (HbA1c) ≤9.5% * Total bilirubin \<2×upper limit of normal (ULN), unless in previously confirmed cases of Gilbert's syndrome * Alanine aminotransferase or aspartate aminotransferase \<3×ULN
Exclusion criteria
* Use of a hepatocyte-targeted siRNA within 365 days before Day 1 (except inclisiran, which is permitted; administration of inclisiran and study drug must be separated by at least 4 weeks) * Use of an antisense oligonucleotide molecule within 3 months before Day 1 * Use of evinacumab within 3 months before Day 1 * Non-response to evinacumab, defined as LDL-C reduction \<15% from baseline after 2 doses * Use of systemic corticosteroids (unless used as replacement therapy for pituitary/adrenal disease with a stable regimen) NOTE: Additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change from Baseline to Month 12 in Fasting LDL-C | Baseline, Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting ApoB | Baseline, Month 12 |
| Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting Non-HDL-C | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting LDL-C | Baseline, Month 12 |
| Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C | Baseline, Month 12 |
| Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting TGs | Baseline, Month 12 |
| Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting ANGPTL3 | Baseline, Month 12 |
| Percent Change from Baseline to Month 12 in Fasting Total Cholesterol | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting Total Cholesterol | Baseline, Month 12 |
| Percent Change from Baseline to Month 12 in Fasting HDL-C | Baseline, Month 12 |
| Change from Baseline to Month 12 in Fasting HDL-C | Baseline, Month 12 |
| Number of Participants who Meet European Union (EU) LDL-C Apheresis Eligibility Criteria (per German Apheresis Working Group) at Month 12 | Month 12 |
| Number of Participants who Meet United States (US) Apheresis Eligibility Criteria (per National Lipid Association) at Month 12 | Month 12 |
| Number of Participants with Fasting LDL-C <100 mg/dL at Month 12 | Month 12 |
| Percent Change from Baseline in Fasting LDL-C Over Time | Baseline, up to Month 12 |
| Change from Baseline in Fasting LDL-C Over Time | Baseline, up to Month 12 |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | Up to 27.5 months |
Contacts
CONTACTMedical Monitor
Outcome results
None listed