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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified May 2026 by Arrowhead Pharmaceuticals
Sponsor
Arrowhead Pharmaceuticals
Information Provided by (Responsible Party)
Arrowhead Pharmaceuticals
Clinicaltrials.gov Identifier
NCT07037771
Other Study ID Numbers:
AROANG3-3001
First Submitted
June 16, 2025
First Posted
June 24, 2025
Last Update Posted
June 9, 2026
Last Verified
May 2026

ClinicalTrials.gov processed this data on June 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Homozygous Familial Hypercholesterolemia
Drug: zodasiran InjectionDrug: zodasiran Injection

Study Design

Study TypeInterventional
Actual Enrollment60 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitlePhase 3 Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
Study Start DateJune 16, 2025
Actual Primary Completion Date1yr 2mos from now
Actual Study Completion Date1yr 2mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
zodasiran
5 doses of zodasiran by subcutaneous (sc) injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period).
Drug: zodasiran Injection
ARO-ANG3 Injection
Placebo
Calculated volume to match active treatment by sc injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period)
Drug: zodasiran Injection
ARO-ANG3 Injection

Outcome Measures

Primary Outcome Measures
  1. Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period)
Secondary Outcome Measures
  1. Change and Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) (Randomized Period)
  2. Change and Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) (Randomized Period)
  3. Change from Baseline to Month 12 in Fasting LDL-C (Randomized Period)
  4. Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C (Randomized Period)
  5. Change and Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) (Randomized Period)
  6. Change and Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) (Randomized Period)
  7. Change and Percent Change from Baseline to Month 12 in Fasting Total Cholesterol (Randomized Period)
  8. Change and Percent Change from Baseline to Month 12 in Fasting High-Density Lipoprotein Cholesterol (HDL-C) (Randomized Period)
  9. Proportion of Participants who Meet European Union (EU) LDL-C Apheresis Eligibility Criteria (per German Apheresis Working Group) at Month 12 (Randomized Period)
  10. Proportion of Participants who Meet United States (US) Apheresis Eligibility Criteria (per National Lipid Association) at Month 12 (Randomized Period)
  11. Proportion of Participants with Fasting LDL-C <100 mg/dL (2.6 mmol/L) at Month 12 (Randomized Period)
  12. Change from Baseline in Fasting LDL-C Over Time (Randomized Period)
  13. Percent Change from Baseline in fasting LDL-C Over Time (Randomized Period)
  14. Percent Change from Baseline to Month 12 in Fasting Lipoprotein(a) [Lp(a)] (Randomized Period)

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsArrowhead Pharmaceuticals
Locations
Research Site 7 | Park Ridge Illinois, United States, 60068Research Site 2 | New York New York, United States, 10029Research Site 1 | Cincinnati Ohio, United States, 45227Research Site 14 | Pittsburgh Pennsylvania, United States, 15213Research Site 13 | Camperdown New South Wales, Australia, 2050Research Site 9 | Saint Leonards New South Wales, Australia, 2065Research Site 21 | Heidelberg Victoria, Australia, 3084Research Site 3 | Nedlands Western Australia, Australia, 6009Research Site 40 | Innsbruck , Austria, 6020Research Site 39 | Linz , Austria, 4021Research Site 42 | Vienna , Austria, 1090Research Site 37 | Vienna , Austria, 1130Research Site 33 | La Louvière , Belgium, 7100Research Site 34 | Leuven , Belgium, 3000Research Site 24 | Cerqueira César São Paulo, Brazil, CEP-05403-000Research Site 5 | Vancouver British Columbia, Canada, V6Z 2H2Research Site 6 | Chicoutimi Quebec, Canada, G7H 7K9Research Site 4 | Québec , Canada, G1V 4W2Research Site 30 | Hradec Králové , Czechia, General E3 500 0Research Site 23 | Paris , France, 75013Research Site 17 | Tbilisi , Georgia, 0159Research Site 18 | Tbilisi , Georgia, 160Research Site 19 | Tbilisi , Georgia, 186Research Site 35 | Berlin , Germany, 13353Research Site 10 | Jerusalem , Israel, 9112001Research Site 15 | Tel Litwinsky , Israel, 5265601Research Site 26 | Kanazawa Ishikawa-ken, Japan, 920-8641Research Site 27 | Suita Osaka, Japan, 564-8565Research Site 20 | Fukushima , Japan, 960-1295Research Site 16 | Okayama , Japan, 700-8558Research Site 22 | Saitama , Japan, 350-0495Research Site 25 | Tokyo , Japan, 113-8510Research Site 12 | Christchurch , New Zealand, 8011Research Site 31 | Riyadh , Saudi Arabia, 12713Research Site 11 | Parktown Johannesburg, South Africa, 2193Research Site 8 | Cape Town , South Africa, 7925Research Site 43 | Barcelona , Spain, 8907Research Site 28 | Córdoba , Spain, 14004Research Site 29 | Madrid , Spain, 28041Research Site 32 | Gothenburg , Sweden, 413 46Research Site 36 | Afyonkarahisar , Turkey (Türkiye), 03200Research Site 41 | Bornova/Izmir , Turkey (Türkiye), 35100Research Site 38 | Melikgazi/Kayseri , Turkey (Türkiye), 38030