Study to evaluate efficacy and safety of inclisiran in children aged 2 to under 12 years of age with homozygous familial hypercholesterolemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Aug 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-514595-41-00

WHO UTN

U1111-1312-7517

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Primary objective is to evaluate the effect of inclisiran compared to placebo on reducing LDL-C [percent change] at Day 330 (Year 1) in children (aged 2 to <12 years) with HoFH and elevated LDL-C

Secondary objectives 3

1. Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1.
2. Evaluate the effect of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time
3. Evaluate the safety and tolerability profile of inclisiran, compared to placebo (for Year 1) and long-term (up to Day 720), in children (aged 2 to <12 years) with HoFH

Conditions and MedDRA coding

homozygous familial hypercholesterolemia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002214-PIP01-17

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female participants, 2 to <12 years of age at screening
2. HoFH diagnosed by genetic confirmation Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible
3. Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
4. On an optimal dose of statin (investigator’s discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)
5. 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.
6. 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 10

1. Documented evidence of a null (negative) mutation in both LDLR alleles
2. Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
3. History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
4. Treatment with mipomersen or lomitapide (within 5 months of screening)
5. Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
6. Heterozygous familial hypercholesterolemia (HeFH)
7. 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)
8. 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)
9. Pregnant or nursing females
10. Recent and/or planned use of other investigational medicinal products or devices

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage change in LDL-C from baseline to Day 330 (Year 1)

Secondary endpoints 3

1. Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)
2. 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)
3. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 18

Locations

6 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 66 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications