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

Arrowhead Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Homozygous Familial Hypercholesterolemia

Treatments: Drug: Placebo; Drug: zodasiran Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT07037771

AROANG3-3001

Details and patient eligibility

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

NOTE: Additional Inclusion/exclusion criteria may apply per protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

zodasiran

Experimental group

Description:

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

Treatment:

Drug: zodasiran Injection

Placebo

Placebo Comparator group

Description:

Calculated volume to match active treatment by sc injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period)

Treatment:

Drug: zodasiran Injection

Drug: Placebo