INCLISIRAN for Heterozygous familial hypercholesterolaemia

Inclusion criteria

• {"criterion_text":"- Obtain informed written consent for the patient to participate in the study, for genetic testing and for the processing of personal data."}
• {"criterion_text":"- Age 10 years-15 years and 6 months."}
• {"criterion_text":"- LDL level from screening visit (V1): (a) LDL≥ 190 mg/dl (>4.921 mmol/L) regardless of family history or (b) LDL ≥160 mg/dl + positive family history (in first-degree relatives and/or siblings: LDL >190 mg/dl (>4.921 mmol/L) and/or with premorbid (i.e. men <55 yrs, women <60 yrs) atherosclerotic cardiovascular disease, and/or corneal stroma, and/or tendonitis) or (c) LDL ≥130 mg/dl + molecularly confirmed mutation in at least one parent."}
• {"criterion_text":"- Negative serum pregnancy test (beta-HCG) in menstruating girls."}
• {"criterion_text":"- Consent to the use of contraceptive methods as described in the study protocol."}

Exclusion criteria

• {"criterion_text":"- Lipid disorders identified as secondary in the investigator's assessment due to: a. BMI ≥ 85th percentile according to the centile grids of Warsaw children (Palczewska-Niedźwiecka); b. poorly compensated diabetes mellitus, defined as HbA1c >8%; c. decompensated hypothyroidism; d. nephrotic syndrome e. anorexia f. liver dysfunction; g. other medical reasons."}
• {"criterion_text":"- Fasting triglycerides > 350 mg/d (l>3.95 mmol/l)."}
• {"criterion_text":"- Uncontrolled hypertension."}
• {"criterion_text":"- Chronic kidney disease (eGFR <30 ml/min/1.73m2)."}
• {"criterion_text":"- Any current treatment in another clinical trial or less than 30 days from the end of treatment in the other trial or 2x the half-life of the drug in the study."}
• {"criterion_text":"- LDL - apheresis within the last month prior to inclusion in the study."}
• {"criterion_text":"- Use of ‘ prohibited’ drugs (see section 7.2.6 of the protocol for details)."}
• {"criterion_text":"- Body weight <23kg"}

Primary endpoints

• {"endpoint_text":"- Number and % of study participants who achieved the therapeutic goal of LDL-C <100 mg/dl (<2.59 mmol/L) at the visit after 104 weeks of treatment (V 13).","definition_or_measurement_approach":"Measured as number and percentage of participants achieving LDL-C <100 mg/dl (<2.59 mmol/L) at visit V13 after 104 weeks of treatment."}

Secondary endpoints

• {"endpoint_text":"- Number and % of study participants who achieved the therapeutic goal of LDL-C <100 mg/dl (<2.59 mmol/L) at visits after 24 (V6) and 60 weeks of treatment (V9).","definition_or_measurement_approach":"Measured as number and percentage achieving LDL-C <100 mg/dl (<2.59 mmol/L) at visits V6 (24 weeks) and V9 (60 weeks)."}
• {"endpoint_text":"- Absolute and percentage change in the following parameters after 24 weeks (V6), 60 weeks (V9) and 104 weeks of treatment (V13): LDL cholesterol, total cholesterol, non-HDL cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, apolipoprotein A1 - relative to pre-treatment measurement with study drug (V4).","definition_or_measurement_approach":"Measured as absolute and percentage change from pre-treatment measurement (V4) for listed lipid parameters at V6 (24 w), V9 (60 w) and V13 (104 w)."}
• {"endpoint_text":"- Change in CIMT (expressed in mm and z-score) after 104 weeks of treatment (V13) versus baseline measurement (V3).","definition_or_measurement_approach":"Measured change in carotid intima-media thickness (CIMT) in mm and z-score at V13 (104 weeks) versus baseline (V3)."}
• {"endpoint_text":"- Absolute values and change (absolute) from baseline for total score based on the PedsQL questionnaire at baseline visit (V3) and after 24 weeks (V6), 60 (V9) and 104 weeks of treatment (V13).","definition_or_measurement_approach":"Measured as absolute total score and absolute change from baseline on the PedsQL questionnaire at V3, V6, V9 and V13."}

Methods

• Leaflets for general practitioners (document: K2_recruitment material_leaflet GPs)
• Leaflets for potential subjects (document: K2_recruitment material_leaflet potential subjects)
• Posters for recruitment (documents: K2_recruitment material_poster P001, K2_recruitment material_poster P002)
• Information cards for potential participants (documents: K2_recruitment material_information card P001, P002)
• Website template for recruitment (document: K2_recruitment material_website template)

Poland

Earliest CTIS Part Ii Submission Date

24-01-2025

Latest Decision Or Authorization Date

06-11-2025

Processing Time Days

286

Number Of Sites

2

Number Of Participants

400

Primary sponsor

Full Name

Medical University Of Lodz

Organisation Type

Educational Institution

Country Of Registered Address

Poland