Studie k posouzení účinnosti a bezpečnosti LIB003 u pacientů s HeFH na perorální léčbě lipidy, kteří potřebují další snížení LDL-C (LIBerate-FH)
Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 3 k vyhodnocení dlouhodobé účinnosti a bezpečnosti LIB003 u pacientů s heterozygotní FH na stabilní terapii snižující hladinu lipidů vyžadující další snížení LDL-C
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.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
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Petah Tikva, Izrael, 49100
- Rabin Medical Center, Beilinson Hospital,
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Jerusalem
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Jerusalem, Jerusalem, Izrael, 12000
- Department of Medicine, Hadassah University Hospital
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Gauteng
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Johannesburg, Gauteng, Jižní Afrika, 2193
- Carbohydrate and Lipid Metabolism Research Unit
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Western Province
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Cape Town, Western Province, Jižní Afrika, 7925
- Division of Lipidology, Department of Medicine University of Cape Town
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Oslo, Norsko, 0586
- Lipid Clinic, Oslo University Hospital
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Ohio
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Cincinnati, Ohio, Spojené státy, 45227
- Metabolic & Atherosclerosis Research Center (MARC)
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Bornova
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Izmir, Bornova, Turecko (Türkiye), 35040
- Ege University Medical School
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: LIB003 (lerodalcibep)
300 mg (1.2 mL) SC Q4W |
300 mg Q4W
Ostatní jména:
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Komparátor placeba: Placebo
1.2 mL SC Q4W |
300 mg Q4W
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula at Week 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Change From Baseline Compared to Placebo in LDL-C Level Calculated by Friedwald Formula Using the Mean of Weeks 22 and 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Level at Week 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Change From Baseline Compared to Placebo in LDL-C Level Calculated by Hopkins Formula Using the Mean of Weeks 22 and 24
Časové okno: Baseline and Weeks 22 and 24
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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. |
Baseline and Weeks 22 and 24
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Change From Baseline Compared to Placebo in LDL-C Level Measured by Preparative Ultracentrifugation at Week 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Change From Baseline Compared to Placebo on Serum Unbound (Free) Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentrations at Week 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Change From Baseline Compared to Placebo in Apolipoprotein B (Apo B) at Week 24
Časové okno: Baseline to Week 24
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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. |
Baseline to Week 24
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Change From Baseline Compared to Placebo in Lipoprotein(a) at Week 24
Časové okno: Baseline and Week 24
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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. |
Baseline and Week 24
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Ředitel studie: David Kallend, MB BCh, LIB Therapeutics
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další identifikační čísla studie
- LIB003-004
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Plánujete sdílet data jednotlivých účastníků (IPD)?
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