Homozygous Familial HypercholesterolemiaPhase 3NCT07037771
A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
A Phase 3 study testing zodasiran Injection in people with Homozygous Familial Hypercholesterolemia, run by Arrowhead Pharmaceuticals at 43 sites in 18 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- zodasiran Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 43 sitesin 18 countries
- Study dates
- 17 Jun 2025to 20 Aug 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
43 sites in 18 countries.
43 sites in 18 countries
Japan6 sites
Research Site 20
Fukushima, 960-1295
Research Site 26
Kanazawa, Ishikawa-ken, 920-8641
Research Site 16
Okayama, 700-8558
Research Site 22
Saitama, 350-0495
Research Site 27
Suita, Osaka, 564-8565
Research Site 25
Tokyo, 113-8510
United States4 sites
Research Site 1
Cincinnati, Ohio, 45227
Research Site 2
New York, New York, 10029
Research Site 7
Park Ridge, Illinois, 60068
Research Site 14
Pittsburgh, Pennsylvania, 15213
Australia4 sites
Research Site 13
Camperdown, New South Wales, 2050
Research Site 21
Heidelberg, Victoria, 3084
Research Site 3
Nedlands, Western Australia, 6009
Research Site 9
Saint Leonards, New South Wales, 2065
Austria4 sites
Research Site 40
Innsbruck, 6020
Research Site 39
Linz, 4021
Research Site 42
Vienna, 1090
Research Site 37
Vienna, 1130
Canada3 sites
Research Site 6
Chicoutimi, Quebec, G7H 7K9
Research Site 4
Québec, G1V 4W2
Research Site 5
Vancouver, British Columbia, V6Z 2H2
Georgia3 sites
Research Site 17
Tbilisi, 0159
Research Site 18
Tbilisi, 160
Research Site 19
Tbilisi, 186
Spain3 sites
Research Site 43
Barcelona, 8907
Research Site 28
Córdoba, 14004
Research Site 29
Madrid, 28041
Turkey (Türkiye)3 sites
Research Site 36
Afyonkarahisar, 03200
Research Site 41
Bornova/Izmir, 35100
Research Site 38
Melikgazi/Kayseri, 38030
Belgium2 sites
Research Site 33
La Louvière, 7100
Research Site 34
Leuven, 3000
Israel2 sites
Research Site 10
Jerusalem, 9112001
Research Site 15
Tel Litwinsky, 5265601
South Africa2 sites
Research Site 8
Cape Town, 7925
Research Site 11
Parktown, Johannesburg, 2193
About this study
Official title: Phase 3 Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
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.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- zodasiran Injection, Placebo
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zodasiran InjectionDrug
Also called ARO-ANG3
ARO-ANG3 Injection
PlaceboDrug
sterile normal saline (0.9% NaCl)
| Study group | Role | What they receive |
|---|---|---|
| zodasiran | Experimental | 5 doses of zodasiran by subcutaneous (sc) injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period). Receives: Drug: zodasiran Injection |
| Placebo | Placebo comparator | Calculated volume to match active treatment by sc injection (randomized period).
4 or 5 doses of zodasiran by sc injection (optional open-label period) Receives: Drug: zodasiran Injection; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change from Baseline to Month 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) (Randomized period)
Measured: Baseline, Month 12
Secondary outcomes (14)
Change and Percent Change from Baseline to Month 12 in Fasting Apolipoprotein B (ApoB) (Randomized Period)
Measured: Baseline, Month 12
Change and Percent Change from Baseline to Month 12 in Fasting Non-High Density Lipoprotein Cholesterol (non-HDL-C) (Randomized Period)
Measured: Baseline, Month 12
Change from Baseline to Month 12 in Fasting LDL-C (Randomized Period)
Measured: Baseline, Month 12
Area Under the Plasma Concentration Versus the Time Curve (AUC) from Baseline to Month 12 for Fasting LDL-C (Randomized Period)
Measured: Baseline, Month 12
Change and Percent Change from Baseline to Month 12 in Fasting Triglycerides (TGs) (Randomized Period)
Measured: Baseline, Month 12
Change and Percent Change from Baseline to Month 12 in Fasting Angiopoietin-like Protein 3 (ANGPTL3) (Randomized Period)
Measured: Baseline, Month 12
Change and Percent Change from Baseline to Month 12 in Fasting Total Cholesterol (Randomized Period)
Measured: Baseline, Month 12
Change and Percent Change from Baseline to Month 12 in Fasting High-Density Lipoprotein Cholesterol (HDL-C) (Randomized Period)
Measured: 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)
Measured: Month 12
Proportion of Participants who Meet United States (US) Apheresis Eligibility Criteria (per National Lipid Association) at Month 12 (Randomized Period)
Measured: Month 12
Proportion of Participants with Fasting LDL-C <100 mg/dL (2.6 mmol/L) at Month 12 (Randomized Period)
Measured: Month 12
Change from Baseline in Fasting LDL-C Over Time (Randomized Period)
Measured: 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)
Measured: 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)
Measured: Baseline, Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2025
- Study start17 Jun 2025
- Primary completion20 Aug 2027 (estimated)
- Study completion20 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07037771
- Sponsor's protocol ID
- AROANG3-3001
- Status last verified
- Aug 2026
- First submitted
- 17 Jun 2025
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No