NCT07037771 · Arrowhead Pharmaceuticals
A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
What this study is about
This conducted at multiple hospitals, randomly assigned, compared against an inactive treatment study will evaluate the effectiveness and safety of zodasiran injected under the skin (SC) injection in subjects 12 years of age and older with genetically or clinically diagnosed Homozygous familial hypercholesterolemia (HoFH).
View original scientific description
This multicenter, randomized, placebo-controlled study will evaluate the efficacy and safety of zodasiran subcutaneous (SC) injection in subjects 12 years of age and older with genetically or clinically diagnosed Homozygous familial hypercholesterolemia (HoFH). After completion of the double blind (DB) treatment period subjects will be eligible to continue in the optional open-label extension (OLE) period of the study. All placebo subjects who opt to continue will transition to active drug during the OLE Period.
Interventions
DRUG
zodasiran Injection
ARO-ANG3 Injection
DRUG
Placebo
sterile normal saline (0.9% NaCl)
Primary outcome measures
Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period)
Time frame: Baseline, Month 12
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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). For adolescents 12 to \<18 years of age, screening LDL-C ≥116 mg/dL (3 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 to include a maximally tolerated statin, ezetimibe, and a PCSK9 inhibitor
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 (except inclisiran, which is permitted; administration of inclisiran and study drug must be separated by at least 4 weeks)
- Use of evinacumab within 3 months before Day 1. Evinacumab use is prohibited during the study.
- 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
Where
- Park Ridge, Illinois
- New York, New York
- Cincinnati, Ohio
- Pittsburgh, Pennsylvania
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 10, 2026 · Source of record for eligibility and locations