Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia

Официальное название

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Children (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol

Обзор

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to \<12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).

Подробное описание

This is a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to \<12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.

Вмешательства

• Препарат Inclisiran
  Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg, inclisiran sodium 180 mg s.c. for participants with body weight \<23 kg to ≥16 kg, or inclisiran sodium 100 mg s.c. for participants with body weight \<16 kg. The dose level is based on the participant's body weight on Day 1 (for Part 1) and Day 360 (for Part 2), respectively.
• Препарат Placebo
  Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)

Первичные конечные точки

• Percentage change in LDL-C from baseline to Day 330 (Year 1) [Срок оценки: Baseline and Day 330]

Вторичные конечные точки (9)

• Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1) [Срок оценки: Baseline, after Day 90 up to Day 330]
• Percent change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Absolute change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]
• Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2) [Срок оценки: Baseline, up to Day 720]

Критерии участия

Критерии включения

• Male or female participants, 2 to <12 years of age at screening
• HoFH diagnosed by genetic confirmation

\- Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also exclusion criteria)

• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• On an optimal dose of statin (investigator's discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)
• Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation
• Participants on a documented regimen of LDL-apheresis for ≥ 3 months before screening will be allowed to continue the apheresis during the study, if needed. The apheresis schedule/settings/duration must be stable prior to screening, are not allowed to change during the double-blind period of the trial and must permit that an apheresis coincides with each study visit.

Критерии исключения

• Documented evidence of a null (negative) mutation in both LDLR alleles
• Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
• History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
• Treatment with mipomersen or lomitapide (within 5 months of screening)
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Heterozygous familial hypercholesterolemia (HeFH)
• Body weight (at the screening and/or randomization (Day 1) visit) <16 kg for participants 6 to <12 years (at screening) or <11 kg for participants 2 to <6 years (at screening)
• Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome)
• Pregnant or nursing females
• Recent and/or planned use of other investigational medicinal products or devices

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• UC San Francisco Medical Center — San Francisco
• Childrens National Hospital — Washington D.C.
• Washington Univ School Of Medicine — St Louis
• Primary Childrens Medical Center — Salt Lake City

Turkey (Türkiye) · 3 центра

• Novartis Investigative Site — Adana
• Novartis Investigative Site — Ankara
• Novartis Investigative Site — Izmir

Греция · 2 центра

• Novartis Investigative Site — Ioannina
• Novartis Investigative Site — Thessaloniki

ЮАР · 2 центра

• Novartis Investigative Site — Bloemfontein
• Novartis Investigative Site — Johannesburg

Тайвань · 2 центра

• Novartis Investigative Site — Taichung
• Novartis Investigative Site — Taipei

Австрия · 1 центр

• Novartis Investigative Site — Vienna

Китай · 1 центр

• Novartis Investigative Site — Пекин

Германия · 1 центр

• Novartis Investigative Site — Frankfurt am Main

Малайзия · 1 центр

• Novartis Investigative Site — Kota Bharu

Нидерланды · 1 центр

• Novartis Investigative Site — Amsterdam

Великобритания · 1 центр

• Novartis Investigative Site — Southampton

Идентификаторы

NCT: NCT06597006 · CKJX839C12304 · 2024-514595-41

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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