A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)

Launched by ARROWHEAD PHARMACEUTICALS · Jun 17, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new medicine called zodasiran to see if it helps people aged 12 and older who have a rare inherited condition called Homozygous Familial Hypercholesterolemia (HoFH). HoFH causes very high levels of “bad” cholesterol (LDL cholesterol) that can lead to heart problems. The study will compare zodasiran to a placebo (a harmless injection with no medicine) to check how well and how safely the medicine works. After the initial part of the study, participants who took the placebo can switch to zodasiran if they want.

To join the study, you need to be at least 12 years old, weigh at least 35 kilograms (about 77 pounds), and have HoFH diagnosed either through genetic testing or based on your cholesterol levels and family history. You should already be on the best cholesterol-lowering treatments your doctor recommends. The study is not open for enrollment yet, but if you join, you will receive regular injections under the skin and have health check-ups to monitor your cholesterol and overall health. Certain health conditions or recent use of other similar treatments might make someone ineligible. This study aims to find better ways to manage HoFH and improve heart health for people living with this condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age ≥12 years, non pregnant, non lactating, do not plan to become pregnant during the study
• • Body weight ≥35 kg at Screening as patients could theoretically be \<35 kg as the study continues.
• • HoFH based on a supportive genetic test or a clinical diagnosis (total cholesterol \>500 mg/dL\[13 mmol/L\] OR treated LDL-C concentration of ≥300 mg/dL \[≥8 mmol/L\] either accompanied by TGs \<300 mg/dL \[3.4 mmol/L\] AND both parents with documented total cholesterol \>250 mg/dL \[6.5 mmol/L\] OR cutaneous or tendinous xanthoma before 10 years of age)
• • LDL-C ≥70 mg/dL (1.8 mmol/L)
• • Hemoglobin A1c (HbA1c) ≤9.5%
• • Total bilirubin \<2xULN, unless in previously confirmed cases of Gilbert's syndrome
• • Alanine aminotransferase or aspartate aminotransferase \<3×ULN
• • On standard of care, maximally tolerated lipid-lowering therapy
• 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 any other investigational agent or device within 30 days or 5 half-lives (whichever is longer) before Day 1
• • Use of systemic corticosteroids (unless used as replacement therapy for pituitary/adrenal disease with a stable regimen)
• • Estimated glomerular filtration rate \<30 mL/min
• • NOTE: Additional Inclusion/exclusion criteria may apply per protocol