Heterozygous Familial HypercholesterolemiaPhase 3LIBerate-FHNCT04797104
Study to Assess the Efficacy and Safety of LIB003 in HeFH Patients on Oral Lipid Therapy Needing Further LDL-C Reduction
A Phase 3 study testing lerodalcibep in people with Heterozygous Familial Hypercholesterolemia, run by LIB Therapeutics LLC at 7 sites in 5 countries.
Trial summary
This study is to assess LDL-C reductions at Week 24 and the mean of Weeks 22 and 24 with monthly Q4W (≤31 days) dosing of LIB003 300 mg administered subcutaneously (SC) compared to placebo in patients 18 years or older with Heterozygous FH on stable diet and oral LDL-C lowering drug therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heterozygous Familial Hypercholesterolemia
- What is being tested?
- lerodalcibep
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 478 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 22 Apr 2021to 5 Dec 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written and signed informed consent prior to any study-specific procedure;
- Weight of ≥40 kg (88 lbs) and body mass index (BMI) ≥17 and ≤42 kg/m2;
- Diagnosis of definite, probable or possible HeFH based either on clinical criteria (Simon Broome register criteria or Dutch Lipid Clinics [DLC] Network Criteria) or genotyping and at the defined eligibility visit (screening or post washout/stabilization)
- LDL-C ≥70 mg/dL (if very-high risk for CVD) or ≥100 mg/dL (if high risk for CVD) and TG ≤400 mg/dL while on stable lipid lowering oral drug therapy (eg, maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency is consistent.
- Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, and unable to tolerate any other allowed oral lipid lowering agent, and thus on no lipid lowering therapy must have an LDL-C ≥190 mg/dL (4.9 mmol/L) at the Screening Visit unless they have a documented pathogenic FH variant;
- Stable diet and other lipid lowering oral therapies besides statins and ezetimibe including bile-acid sequestrants, OM-3 compounds, fenofibrate, bezafibrate, nicotinic acid and bempedoic acid or combinations thereof for at least 4 weeks
- Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥4 weeks after the last dose; for those on a dose of 300 mg or 420 mg Q4W (≤31 days) the washout period is ≥8 weeks following last dose;
- Females of childbearing potential must be using a highly effective form of contraception if sexually active and have negative urine pregnancy test at the last Screening Visit
Who cannot join
- Use of prohibited oral lipid lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of the Screening Visit or LDL/plasma apheresis within 2 months prior to Day 1;
- Documented history of HoFH defined clinically or genetically
- History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator.
- Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit;
- Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
- Active liver disease or hepatic dysfunction, history of liver transplant, and/or AST or ALT >2.5 × the ULN
Show all 12Show fewer
- Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by TSH <LLN or >1.5 × ULN, respectively,
- Uncontrolled Type 1 or Type 2 DM (fasting glucose≥200 mg/dL or HbA1c of ≥9%;
- Planned cardiac surgery or revascularization;
- New York Heart Association III-IV heart failure
- Previous treatment with LIB003 or any adnectin product;
- Any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Israel2 sites
Department of Medicine, Hadassah University Hospital
Jerusalem, Jerusalem, 12000
Rabin Medical Center, Beilinson Hospital,
Petah Tikva, 49100
South Africa2 sites
Division of Lipidology, Department of Medicine University of Cape Town
Cape Town, Western Province, 7925
Carbohydrate and Lipid Metabolism Research Unit
Johannesburg, Gauteng, 2193
United States1 site
Metabolic & Atherosclerosis Research Center (MARC)
Cincinnati, Ohio, 45227
Turkey (Türkiye)1 site
Ege University Medical School
Izmir, Bornova, 35040
About this study
Official title: Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Heterozygous FH Patients on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction
This study is to assess LDL-C reductions at Week 24 and the mean of Weeks 22 and 24 with monthly Q4W (≤31 days) dosing of LIB003 300 mg administered subcutaneously (SC) compared to placebo in patients 18 years or older with Heterozygous FH on stable diet and oral LDL-C lowering drug therapy.
Read the detailed description
A randomized, double-blind, placebo-controlled, Phase 3 study of 24 weeks duration. Approximately 600 males and females aged ≥18 years with clinical or genetic heterozygous FH who fulfill the inclusion and exclusion criteria will be enrolled. Patients will be randomized in a 2:1 ratio to LIB003 (400 patients) or placebo (200 patients) administered SC Q4W (≤31 days). The study will consist of a Screening Period and a Treatment Period. The total study duration will be up to 35 weeks which includes up to an 11-week Screening Period (which may include up to a 8-week washout) and 24 weeks of study drug treatment.
- Being tested
- lerodalcibep
- Keywords
- lerodalcibep, PCSK9 inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lerodalcibepDrug
Also called LIB003
300 mg Q4W
| Study group | Role | What they receive |
|---|---|---|
| LIB003 (lerodalcibep) | Experimental | 300 mg (1.2 mL) SC Q4W Receives: Drug: lerodalcibep |
| Placebo | Placebo comparator | 1.2 mL SC Q4W Receives: Drug: lerodalcibep |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in LDL-C (calculated by the Friedwald formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Week 24
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula Using the Mean of Weeks 22 and 24
Blood samples were collected at baseline Week 22 and Week 24 to determine mean percent change in LDL-C (calculated by the Friedwald formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Week 24
Secondary outcomes (6)
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Level at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in LDL-C (calculated by the Hopkins formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Week 24
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Formula Using the Mean of Weeks 22 and 24
Blood samples were collected at baseline Week 22 and Week 24 to determine mean percent change in LDL-C (calculated by the Friedwald formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Weeks 22 and 24
Change From Baseline Compared to Placebo in LDL-C Level Measured by Preparative Ultracentrifugation at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in LDL-C (measured by preparative ultracentrifugation). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Week 24
Change From Baseline Compared to Placebo on Serum Unbound (Free) Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentrations at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in free PCSK9 concentrations. Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Measured: Baseline and Week 24
Change From Baseline Compared to Placebo in Apolipoprotein B (Apo B) at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in apo B. Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline apo B value as covariate.
Measured: Baseline to Week 24
Change From Baseline Compared to Placebo in Lipoprotein(a) at Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in Lp(a). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline Lp(a) value as covariate.
Measured: Baseline and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start22 Apr 2021
- Primary completion30 Jul 2023
- Study completion5 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heterozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- 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
- Model description
- Randomized double blind placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 478 participants (actual)
Sponsor and investigators
- Lead sponsor
- LIB Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Responsible party
- Sponsor
- Investigators
- David Kallend, MB BCh, Study director, LIB Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04797104
- Sponsor's protocol ID
- LIB003-004
- Acronym
- LIBerate-FH
- Status last verified
- Aug 2026
- First submitted
- 10 Mar 2021
- Last updated
- 27 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Long-Term Efficacy and Safety of LIB003 in Heterozygous FH Patients on Stable Lipid-Lowering Therapy Requiring Additional LDL-C Reduction
- ClinicalTrials.gov ID
- NCT04797104
- Acronym / sponsor ID
- LIBerate-FH / LIB003-004
- Keywords
- lerodalcibep, PCSK9 inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 478 participants (actual)
- Lead sponsor
- LIB Therapeutics LLCIndustry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Study start
- 22 Apr 2021 (actual)
- Primary completion
- 30 Jul 2023 (actual)
- Study completion
- 5 Dec 2023 (actual)
- First posted
- 15 Mar 2021 (actual)
- Results
- Posted 28 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to assess LDL-C reductions at Week 24 and the mean of Weeks 22 and 24 with monthly Q4W (≤31 days) dosing of LIB003 300 mg administered subcutaneously (SC) compared to placebo in patients 18 years or older with Heterozygous FH on stable diet and oral LDL-C lowering drug therapy.
Detailed description
A randomized, double-blind, placebo-controlled, Phase 3 study of 24 weeks duration. Approximately 600 males and females aged ≥18 years with clinical or genetic heterozygous FH who fulfill the inclusion and exclusion criteria will be enrolled. Patients will be randomized in a 2:1 ratio to LIB003 (400 patients) or placebo (200 patients) administered SC Q4W (≤31 days). The study will consist of a Screening Period and a Treatment Period. The total study duration will be up to 35 weeks which includes up to an 11-week Screening Period (which may include up to a 8-week washout) and 24 weeks of study drug treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized double blind placebo controlled
| Arm | Type | Receives |
|---|---|---|
| LIB003 (lerodalcibep) | Experimental | Drug: lerodalcibep300 mg (1.2 mL) SC Q4W |
| Placebo | Placebo comparator | Drug: lerodalcibep1.2 mL SC Q4W |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Provision of written and signed informed consent prior to any study-specific procedure;
- Weight of ≥40 kg (88 lbs) and body mass index (BMI) ≥17 and ≤42 kg/m2;
- Diagnosis of definite, probable or possible HeFH based either on clinical criteria (Simon Broome register criteria or Dutch Lipid Clinics [DLC] Network Criteria) or genotyping and at the defined eligibility visit (screening or post washout/stabilization)
- LDL-C ≥70 mg/dL (if very-high risk for CVD) or ≥100 mg/dL (if high risk for CVD) and TG ≤400 mg/dL while on stable lipid lowering oral drug therapy (eg, maximally tolerated statin with or without ezetimibe); Patients unable to tolerate approved doses of a statin may take lower than approved doses and less frequently than daily as long as the dose and dosing frequency is consistent.
- Patients with documentation of inability to tolerate any statin at any dose, or history of rhabdomyolysis, and unable to tolerate any other allowed oral lipid lowering agent, and thus on no lipid lowering therapy must have an LDL-C ≥190 mg/dL (4.9 mmol/L) at the Screening Visit unless they have a documented pathogenic FH variant;
Key exclusion criteria (12 listed)
- Use of prohibited oral lipid lowering agents mipomersen or lomitapide within 6 months of screening, gemfibrozil within 6 weeks of the Screening Visit or LDL/plasma apheresis within 2 months prior to Day 1;
- Documented history of HoFH defined clinically or genetically
- History of any prior or active clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator.
- Females of childbearing potential who are sexually active, not using or unwilling to use a highly effective form of contraception, pregnant or breastfeeding, or who have a positive urine pregnancy test at the last Screening Visit;
- Moderate to severe renal dysfunction, defined as an eGFR <30 mL/min/1.73m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lerodalcibepAlso: LIB003300 mg Q4W | Drug | LIB003 (lerodalcibep), Placebo |
Primary outcome
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula at Week 24
Time frame: Baseline and Week 24
Blood samples were collected at baseline and Week 24 to determine mean percent change in LDL-C (calculated by the Friedwald formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula Using the Mean of Weeks 22 and 24
Time frame: Baseline and Week 24
Blood samples were collected at baseline Week 22 and Week 24 to determine mean percent change in LDL-C (calculated by the Friedwald formula). Percent change from baseline determined using analysis of covariance (ANCOVA) model with treatment and CVD status as factors and baseline LDL-C value as covariate.
6 secondary outcomes
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Level at Week 24
Time frame: Baseline and Week 24
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Formula Using the Mean of Weeks 22 and 24
Time frame: Baseline and Weeks 22 and 24
Change From Baseline Compared to Placebo in LDL-C Level Measured by Preparative Ultracentrifugation at Week 24
Time frame: Baseline and Week 24
Change From Baseline Compared to Placebo on Serum Unbound (Free) Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentrations at Week 24
Time frame: Baseline and Week 24
Change From Baseline Compared to Placebo in Apolipoprotein B (Apo B) at Week 24
Time frame: Baseline to Week 24
Change From Baseline Compared to Placebo in Lipoprotein(a) at Week 24
Time frame: Baseline and Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Kallend, MB BCh study director
LIB Therapeutics
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing lerodalcibep in people with Heterozygous Familial Hypercholesterolemia, run by LIB Therapeutics LLC at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Israel, South Africa, United States, Norway, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula at Week 24 (time frame: Baseline and Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.