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

NCT ID: NCT07037771

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-17

Study Completion Date

2027-08-20

Brief Summary

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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.

Detailed Description

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Conditions

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Homozygous Familial Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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zodasiran

5 doses of zodasiran by subcutaneous (sc) injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period).

Group Type EXPERIMENTAL

zodasiran Injection

Intervention Type DRUG

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)

Group Type PLACEBO_COMPARATOR

zodasiran Injection

Intervention Type DRUG

ARO-ANG3 Injection

Placebo

Intervention Type DRUG

sterile normal saline (0.9% NaCl)

Interventions

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zodasiran Injection

ARO-ANG3 Injection

Intervention Type DRUG

Placebo

sterile normal saline (0.9% NaCl)

Intervention Type DRUG

Other Intervention Names

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ARO-ANG3

Eligibility Criteria

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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)
* 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

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
* Use of evinacumab within 3 months before Day 1
* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arrowhead Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site 7

Park Ridge, Illinois, United States

Site Status RECRUITING

Research Site 2

New York, New York, United States

Site Status RECRUITING

Research Site 1

Cincinnati, Ohio, United States

Site Status RECRUITING

Research Site 3

Nedlands, Western Australia, Australia

Site Status RECRUITING

Research Site 5

Vancouver, British Columbia, Canada

Site Status RECRUITING

Research Site 6

Chicoutimi, Quebec, Canada

Site Status RECRUITING

Research Site 4

Québec, Quebec, Canada

Site Status RECRUITING

Research Site 8

Cape Town, , South Africa

Site Status RECRUITING

Countries

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United States Australia Canada South Africa

Central Contacts

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Medical Monitor

Role: CONTACT

Phone: 626-304-3400

Email: [email protected]

Other Identifiers

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AROANG3-3001

Identifier Type: -

Identifier Source: org_study_id