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Recruiting NCT07037771

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

Phase III Interventional Homozygous Familial Hypercholesterolemia

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: zodasiran Injection, Placebo.
Who it may be relevant to
Registry conditions: Homozygous Familial Hypercholesterolemia. Basic parameters: from 12 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Australia, Austria, Belgium, Brazil +13
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • Drug zodasiran Injection
    ARO-ANG3 Injection
  • Drug Placebo
    sterile normal saline (0.9% NaCl)

Primary outcome measures

  • Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period) [Time frame: Baseline, Month 12]
Secondary outcome measures (12)
  • Change and Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) (Randomized Period) [Time frame: Baseline, Month 12]
  • Change and Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) (Randomized Period) [Time frame: Baseline, Month 12]
  • Change from Baseline to Month 12 in Fasting LDL-C (Randomized Period) [Time frame: Baseline, Month 12]
  • Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C (Randomized Period) [Time frame: Baseline, Month 12]
  • Change and Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) (Randomized Period) [Time frame: Baseline, Month 12]
  • Change and Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) (Randomized Period) [Time frame: Baseline, Month 12]
  • Change and Percent Change from Baseline to Month 12 in Fasting Total Cholesterol (Randomized Period) [Time frame: Baseline, Month 12]
  • Change and Percent Change from Baseline to Month 12 in Fasting High-Density Lipoprotein Cholesterol (HDL-C) (Randomized Period) [Time frame: Baseline, Month 12]
  • Proportion of Participants who Meet European Union (EU) LDL-C Apheresis Eligibility Criteria (per German Apheresis Working Group) at Month 12 (Randomized Period) [Time frame: Month 12]
  • Proportion of Participants who Meet United States (US) Apheresis Eligibility Criteria (per National Lipid Association) at Month 12 (Randomized Period) [Time frame: Month 12]
  • Proportion of Participants with Fasting LDL-C <100 mg/dL (2.6 mmol/L) at Month 12 (Randomized Period) [Time frame: Month 12]
  • Change from Baseline in Fasting LDL-C Over Time (Randomized Period) [Time frame: Baseline, Day 1, Months 1, 2, 3, 4.5, 6, 7.5, 9, 10.5, and 12]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Japan · 6 centers
  • Research Site 26 — Kanazawa
  • Research Site 27 — Suita
  • Research Site 20 — Fukushima
  • Research Site 16 — Okayama
  • Research Site 22 — Saitama
  • Research Site 25 — Tokyo
United States · 4 centers
  • Research Site 7 — Park Ridge
  • Research Site 2 — New York
  • Research Site 1 — Cincinnati
  • Research Site 14 — Pittsburgh
Australia · 4 centers
  • Research Site 13 — Camperdown
  • Research Site 9 — Saint Leonards
  • Research Site 21 — Heidelberg
  • Research Site 3 — Nedlands
Austria · 4 centers
  • Research Site 40 — Innsbruck
  • Research Site 39 — Linz
  • Research Site 42 — Vienna
  • Research Site 37 — Vienna
Canada · 3 centers
  • Research Site 5 — Vancouver
  • Research Site 6 — Chicoutimi
  • Research Site 4 — Québec
Georgia · 3 centers
  • Research Site 17 — Tbilisi
  • Research Site 18 — Tbilisi
  • Research Site 19 — Tbilisi
Spain · 3 centers
  • Research Site 43 — Barcelona
  • Research Site 28 — Córdoba
  • Research Site 29 — Madrid
Turkey (Türkiye) · 3 centers
  • Research Site 36 — Afyonkarahisar
  • Research Site 41 — Bornova/Izmir
  • Research Site 38 — Melikgazi/Kayseri
Belgium · 2 centers
  • Research Site 33 — La Louvière
  • Research Site 34 — Leuven
Israel · 2 centers
  • Research Site 10 — Jerusalem
  • Research Site 15 — Tel Litwinsky
South Africa · 2 centers
  • Research Site 11 — Parktown
  • Research Site 8 — Cape Town
Brazil · 1 center
  • Research Site 24 — Cerqueira César
Czechia · 1 center
  • Research Site 30 — Hradec Králové
France · 1 center
  • Research Site 23 — Paris
Germany · 1 center
  • Research Site 35 — Berlin
New Zealand · 1 center
  • Research Site 12 — Christchurch
Saudi Arabia · 1 center
  • Research Site 31 — Riyadh
Sweden · 1 center
  • Research Site 32 — Gothenburg

Identifiers

NCT: NCT07037771 · AROANG3-3001

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗