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

NCT07037771 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AROANG3-3001
• Study Type: interventional
• Target: 60
• Locations: 16 countries
• Sites: 35

Brief Summary

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.

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period)

  Baseline, Month 12

Secondary Outcomes (14)

• Change and Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) (Randomized Period)

  Baseline, Month 12

• Change and Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) (Randomized Period)

  Baseline, Month 12

• Change from Baseline to Month 12 in Fasting LDL-C (Randomized Period)

  Baseline, Month 12

• Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C (Randomized Period)

  Baseline, Month 12

• Change and Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) (Randomized Period)

  Baseline, Month 12

Study Arms (2)

zodasiran

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

zodasiran Injection DRUG

ARO-ANG3 Injection

Also known as: ARO-ANG3

Placebo; zodasiran

Placebo DRUG

sterile normal saline (0.9% NaCl)

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (35)

Research Site 7

Park Ridge, Illinois, 60068, United States

RECRUITING

Research Site 2

New York, New York, 10029, United States

RECRUITING

Research Site 1

Cincinnati, Ohio, 45227, United States

RECRUITING

Research Site 14

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Research Site 13

Camperdown, New South Wales, 2050, Australia

RECRUITING

Research Site 9

Saint Leonards, New South Wales, 2065, Australia

RECRUITING

Research Site 21

Heidelberg, Victoria, 3084, Australia

RECRUITING

Research Site 3

Nedlands, Western Australia, 6009, Australia

RECRUITING

Research Site 33

La Louvière, 7100, Belgium

RECRUITING

Research Site 34

Leuven, 3000, Belgium

RECRUITING

Research Site 24

Cerqueira César, São Paulo, CEP-05403-000, Brazil

RECRUITING

Research Site 5

Vancouver, British Columbia, V6Z 2H2, Canada

RECRUITING

Research Site 6

Chicoutimi, Quebec, G7H 7K9, Canada

RECRUITING

Research Site 4

Québec, G1V 4W2, Canada

RECRUITING

Research Site 30

Hradec Králové, General E3 500 0, Czechia

RECRUITING

Research Site 23

Paris, 75013, France

RECRUITING

Research Site 17

Tbilisi, 0159, Georgia

RECRUITING

Research Site 18

Tbilisi, 160, Georgia

RECRUITING

Research Site 19

Tbilisi, 186, Georgia

RECRUITING

Research Site 35

Berlin, 13353, Germany

RECRUITING

Research Site 10

Jerusalem, 9112001, Israel

RECRUITING

Research Site 15

Tel Litwinsky, 5265601, Israel

RECRUITING

Research Site 26

Kanazawa, Ishikawa-ken, 920-8641, Japan

RECRUITING

Research Site 27

Suita, Osaka, 564-8565, Japan

RECRUITING

Research Site 20

Fukushima, 960-1295, Japan

RECRUITING

Research Site 16

Okayama, 700-8558, Japan

RECRUITING

Research Site 22

Saitama, 350-0495, Japan

RECRUITING

Research Site 25

Tokyo, 113-8510, Japan

RECRUITING

Research Site 12

Christchurch, 8011, New Zealand

RECRUITING

Research Site 31

Riyadh, 12713, Saudi Arabia

RECRUITING

Research Site 11

Parktown, Johannesburg, 2193, South Africa

RECRUITING

Research Site 8

Cape Town, 7925, South Africa

RECRUITING

Research Site 28

Córdoba, 14004, Spain

RECRUITING

Research Site 29

Madrid, 28041, Spain

RECRUITING

Research Site 32

Gothenburg, 413 46, Sweden

RECRUITING

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

zodasiran

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Medical Monitor

CONTACT

626-304-3400; YOSEMITE@arrowheadpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: June 25, 2025
• Study Start: June 17, 2025
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): August 20, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

IL (2); NZ (1); JP (6); US (4); AU (4); GE (3); CA (3); ES (2); BR (1); FR (1); CZ (1); SA (1); ZA (2); SE (1); BE (2); DE (1)