INCLISIRAN for Homozygous familial hypercholesterolemia

Inclusion criteria

• {"criterion_text":"- Male or female participants, 2 to <12 years of age at screening\n- HoFH diagnosed by genetic confirmation Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible\n- Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening\n- On an optimal dose of statin (investigator’s discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)\n- Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days (≥90 days for evinacumab) before screening with no planned medication or dose changes during study participation.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Documented evidence of a null (negative) mutation in both LDLR alleles\n- Recent and/or planned use of other investigational medicinal products or devices\n- Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9\n- History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)\n- Treatment with mipomersen or lomitapide (within 5 months of screening)\n- Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome\n- Heterozygous familial hypercholesterolemia (HeFH)\n- 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)\n- 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)\n- Pregnant or nursing females"}

Primary endpoints

• {"endpoint_text":"- Percentage change in LDL-C from baseline to Day 330 (Year 1)","definition_or_measurement_approach":"Percent change in LDL-C from baseline to Day 330 (Year 1); comparison of inclisiran versus placebo at Day 330."}

Secondary endpoints

• {"endpoint_text":"- Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)","definition_or_measurement_approach":"Time-adjusted percent change in LDL-C from baseline measured after Day 90 and up to Day 330 (Year 1)."}
• {"endpoint_text":"- Percent change and absolute change in LDL-C, PCSK9, total cholesterol, Apo B, non-HDL-C, Lp(a), triglycerides, HDL-C, VLDL-C and Apo A1 from baseline to each assessment time up to Day 720 (Year 2)","definition_or_measurement_approach":"Percent and absolute changes from baseline for listed lipid and protein biomarkers at each assessment through Day 720 (Year 2)."}
• {"endpoint_text":"- Incidence, severity and relationship to study drug of treatment-emergent AEs and SAEs; vital signs; laboratory parameters; ADA measurement; growth (height, weight, BMI); pubertal development (sexual hormones and Tanner staging)","definition_or_measurement_approach":"Safety and tolerability assessments including treatment-emergent AEs/SAEs, vitals, labs, anti-drug antibody (ADA) measurement, growth parameters and pubertal development assessments (hormones, Tanner staging) through follow-up."}

Netherlands

Earliest CTIS Part Ii Submission Date

12-12-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

498

Number Of Sites

1

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

11-12-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

503

Number Of Sites

1

Number Of Participants

1

Germany

Earliest CTIS Part Ii Submission Date

29-11-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

516

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

13-12-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

501

Number Of Sites

1

Number Of Participants

1

Austria

Earliest CTIS Part Ii Submission Date

12-12-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

502

Number Of Sites

1

Number Of Participants

1

Greece

Earliest CTIS Part Ii Submission Date

02-10-2024

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

583

Number Of Sites

2

Number Of Participants

3

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA RDS Hellas Single Member S.A.

Responsibilities

[{"code":"1"},{"code":"15","value":"Start up CTA role actions"}]

Name

Medpace Inc.

Responsibilities

[{"code":"4"}]

Name

Syneos Health Inc.

Responsibilities

[{"code":"1"}]

Name

Icon Clinical Research Limited

Responsibilities

[{"code":"1"}]

Name

IQVIA Limited

Responsibilities

[{"code":"3"}]

Name

Parexel International (IRL) Limited

Responsibilities

[{"code":"12"}]

Name

Labcorp Pharmaceutical Research And Development (Shanghai) Co. Ltd.

Responsibilities

[{"code":"4"}]

Name

WCG Clinical Inc.

Responsibilities

[{"code":"10"}]

Third parties

• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"[{\"code\":\"1\"},{\"code\":\"15\",\"value\":\"Start up CTA role actions\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Medpace Reference Laboratories China","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"[{\"code\":\"1\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"[{\"code\":\"1\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"[{\"code\":\"3\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Shanghai Xiawei Medical Laboratory Co. Ltd.","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Singapore","full_name":"Medpace Laboratories Singapore","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Industry"}
• {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"[{\"code\":\"8\"}]","organisation_type":"Patient organisation/association"}
• {"country":"United States","full_name":"Simpleshow USA Corp.","duties_or_roles":"[{\"code\":\"15\",\"value\":\"Patient engagement video material\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"[{\"code\":\"1\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"ABF Pharmaceutical Services GmbH","duties_or_roles":"[{\"code\":\"15\",\"value\":\"Local depot storage & distribution of AxMP to sites/final Rec.+Destruction\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"[{\"code\":\"10\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"[{\"code\":\"12\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Labcorp Pharmaceutical Research And Development (Shanghai) Co. Ltd.","duties_or_roles":"[{\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}