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

Phase 3RecruitingNCT07037771

Arrowhead Pharmaceuticals60 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

zodasiran Injection

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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 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

Locations (16)

Research Site 7

Park Ridge, Illinois, United States

RECRUITING

Research Site 2

New York, New York, United States

RECRUITING

Research Site 1

Cincinnati, Ohio, United States

RECRUITING

Research Site 14

Pittsburgh, Pennsylvania, United States

RECRUITING

Research Site 13

Camperdown, New South Wales, Australia

RECRUITING

Research Site 9

Saint Leonards, New South Wales, Australia

RECRUITING

Research Site 3

Nedlands, Western Australia, Australia

RECRUITING

Research Site 5

Vancouver, British Columbia, Canada

RECRUITING

Research Site 6

Chicoutimi, Quebec, Canada

RECRUITING

Research Site 4

Québec, Quebec, Canada

RECRUITING

...and 6 more locations

Outcomes

Primary Outcomes

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

Time frame: Baseline, Month 12

Secondary Outcomes

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

Time frame: Baseline, Month 12

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

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

Time frame: Baseline, Month 12

Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) (Randomized Period)

Time frame: Baseline, Month 12

Percent Change from Baseline to Month 12 in Fasting Total Cholesterol (Randomized Period)

Time frame: Baseline, Month 12

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

Percent 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

Percent Change from Baseline to Month 12 in Fasting Lipoprotein(a) [Lp(a)] (Randomized Period)

Time frame: Baseline, Month 12

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

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts