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Phase 3 zodasiran for adolescents and adults with homozygous familial hypercholesterolemia

Phase 3 Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)

Phase 3 Interventional Arrowhead Pharmaceuticals · NCT07037771

This trial will test whether subcutaneous zodasiran injections can lower LDL cholesterol in people age 12 and older who have homozygous familial hypercholesterolemia.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment60 (estimated)
Ages12 Years and up
SexAll
SponsorArrowhead Pharmaceuticals Industry-sponsored
Drugs / interventionsevinacumab
Locations35 sites (Park Ridge, Illinois and 34 other locations)
Trial IDNCT07037771 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, double-blind, placebo-controlled Phase 3 trial gives subcutaneous zodasiran injections to participants aged 12 and older with genetically or clinically confirmed HoFH while they remain on maximally tolerated lipid-lowering therapy. Participants are randomized to zodasiran or placebo for a double-blind period, after which eligible subjects may join an optional open-label extension where all placebo participants can receive active drug. The study monitors LDL-C changes and safety labs including liver enzymes and HbA1c, and applies specific inclusion thresholds for LDL-C and body weight. Adolescents and adults meeting genetic or clinical diagnostic criteria and other laboratory limits are enrolled, with exclusions for pregnancy and certain liver abnormalities.

Who should consider this trial

Good fit: Ideal candidates are people aged 12 years and older (weighing ≥35 kg) with genetically or clinically confirmed HoFH who have LDL-C above the protocol thresholds and are on maximally tolerated lipid-lowering therapy, and who are not pregnant or lactating.

Not a fit: Patients who do not meet the HoFH genetic/clinical criteria or LDL thresholds, who have significant liver dysfunction, are pregnant or lactating, or cannot adhere to study visits are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, zodasiran could offer a new way to substantially lower LDL cholesterol in HoFH patients who remain inadequately controlled on current therapies, potentially reducing long-term cardiovascular risk.

How similar studies have performed: Other RNA-based and antibody lipid-lowering therapies have successfully reduced LDL in related populations, but phase 3 evidence specifically for zodasiran in HoFH is not yet established.

Eligibility criteria

Show full inclusion / exclusion 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). 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 this trial is running

Park Ridge, Illinois and 34 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Homozygous Familial Hypercholesterolemia
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.