Actively Recruiting

Phase 3
Age: 12Years +
All Genders
NCT07037771

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

Led by Arrowhead Pharmaceuticals · Updated on 2026-05-06

60

Participants Needed

35

Research Sites

113 weeks

Total Duration

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AI-Summary

What this Trial Is About

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

Official Title

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

Who Can Participate

Age: 12Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 12 years or older, not pregnant or breastfeeding, and not planning pregnancy during the study
  • Body weight of at least 35 kg at screening
  • Diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) confirmed by genetic test or clinical diagnosis with specific cholesterol criteria
  • LDL cholesterol level of at least 70 mg/dL for adults, or at least 116 mg/dL for adolescents aged 12 to under 18 years
  • Hemoglobin A1c level of 9.5% or less
  • Total bilirubin less than twice the upper limit of normal unless Gilbert's syndrome is confirmed
  • Alanine aminotransferase and aspartate aminotransferase levels less than three times the upper limit of normal
  • Currently receiving maximally tolerated standard lipid-lowering therapy including statins, ezetimibe, and a PCSK9 inhibitor
Not Eligible

You will not qualify if you...

  • Use of hepatocyte-targeted siRNA treatments within 365 days before Day 1, except for inclisiran with at least 4 weeks between treatments
  • Use of antisense oligonucleotide molecules within 3 months before Day 1, except inclisiran with at least 4 weeks separation
  • Use of evinacumab within 3 months before Day 1; evinacumab is not allowed during the study
  • Failure to respond to evinacumab treatment, defined as less than 15% reduction in LDL cholesterol after 2 doses
  • Use of any other investigational drugs or devices within 30 days or 5 half-lives before Day 1
  • Use of systemic corticosteroids unless as stable replacement therapy for pituitary or adrenal disease
  • Estimated glomerular filtration rate below 30 mL/min
  • Additional criteria may apply according to protocol

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 35 locations

1

Research Site 7

Park Ridge, Illinois, United States, 60068

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2

Research Site 2

New York, New York, United States, 10029

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3

Research Site 1

Cincinnati, Ohio, United States, 45227

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4

Research Site 14

Pittsburgh, Pennsylvania, United States, 15213

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5

Research Site 13

Camperdown, New South Wales, Australia, 2050

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6

Research Site 9

Saint Leonards, New South Wales, Australia, 2065

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7

Research Site 21

Heidelberg, Victoria, Australia, 3084

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8

Research Site 3

Nedlands, Western Australia, Australia, 6009

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9

Research Site 33

La Louvière, Belgium, 7100

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10

Research Site 34

Leuven, Belgium, 3000

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11

Research Site 24

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

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12

Research Site 5

Vancouver, British Columbia, Canada, V6Z 2H2

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13

Research Site 6

Chicoutimi, Quebec, Canada, G7H 7K9

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14

Research Site 4

Québec, Canada, G1V 4W2

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15

Research Site 30

Hradec Králové, Czechia, General E3 500 0

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16

Research Site 23

Paris, France, 75013

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17

Research Site 17

Tbilisi, Georgia, 0159

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18

Research Site 18

Tbilisi, Georgia, 160

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19

Research Site 19

Tbilisi, Georgia, 186

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20

Research Site 35

Berlin, Germany, 13353

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21

Research Site 10

Jerusalem, Israel, 9112001

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22

Research Site 15

Tel Litwinsky, Israel, 5265601

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23

Research Site 26

Kanazawa, Ishikawa-ken, Japan, 920-8641

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24

Research Site 27

Suita, Osaka, Japan, 564-8565

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25

Research Site 20

Fukushima, Japan, 960-1295

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26

Research Site 16

Okayama, Japan, 700-8558

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27

Research Site 22

Saitama, Japan, 350-0495

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28

Research Site 25

Tokyo, Japan, 113-8510

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29

Research Site 12

Christchurch, New Zealand, 8011

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30

Research Site 31

Riyadh, Saudi Arabia, 12713

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31

Research Site 11

Parktown, Johannesburg, South Africa, 2193

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32

Research Site 8

Cape Town, South Africa, 7925

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33

Research Site 28

Córdoba, Spain, 14004

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34

Research Site 29

Madrid, Spain, 28041

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35

Research Site 32

Gothenburg, Sweden, 413 46

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Research Team

M

Medical Monitor

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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