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.
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period) — Baseline, Month 12
Trial sites (43)
Facility
City
Region
Status
Research Site 7
Park Ridge
Illinois
Research Site 2
New York
New York
Research Site 1
Cincinnati
Ohio
Research Site 14
Pittsburgh
Pennsylvania
Research Site 13
Camperdown
New South Wales
Research Site 9
Saint Leonards
New South Wales
Research Site 21
Heidelberg
Victoria
Research Site 3
Nedlands
Western Australia
Research Site 40
Innsbruck
Austria
Research Site 39
Linz
Austria
Research Site 42
Vienna
Austria
Research Site 37
Vienna
Austria
Research Site 33
La Louvière
Belgium
Research Site 34
Leuven
Belgium
Research Site 24
Cerqueira César
São Paulo
Research Site 5
Vancouver
British Columbia
Research Site 6
Chicoutimi
Quebec
Research Site 4
Québec
Canada
Research Site 30
Hradec Králové
Czechia
Research Site 23
Paris
France
Research Site 17
Tbilisi
Georgia
Research Site 18
Tbilisi
Georgia
Research Site 19
Tbilisi
Georgia
Research Site 35
Berlin
Germany
Research Site 10
Jerusalem
Israel
Research Site 15
Tel Litwinsky
Israel
Research Site 26
Kanazawa
Ishikawa-ken
Research Site 27
Suita
Osaka
Research Site 20
Fukushima
Japan
Research Site 16
Okayama
Japan
Research Site 22
Saitama
Japan
Research Site 25
Tokyo
Japan
Research Site 12
Christchurch
New Zealand
Research Site 31
Riyadh
Saudi Arabia
Research Site 11
Parktown
Johannesburg
Research Site 8
Cape Town
South Africa
Research Site 43
Barcelona
Spain
Research Site 28
Córdoba
Spain
Research Site 29
Madrid
Spain
Research Site 32
Gothenburg
Sweden
+ 3 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.