Comparison of inclisiran or alirocumab to standard therapy in pediatric heterozygous familial hypercholesterolemia (HeFH) – the head-to-head PICOLO-FH clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Lodz

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Jun 2025 → ongoing

Decision date (initial)

2025-02-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assessment the efficacy of treatment with alirocumab (S.C.) and rosuvastatin (P.O.) or inclisiran (S.C.) and rosuvastatin (P.O.), compared with standard rosuvastatin (P.O.) therapy, in achieving the therapeutic goal of LDL-C <100 mg/dl after 104 weeks of treatment in paediatric population with heterozygous familial hypercholesterolaemia.

Secondary objectives 1

1. To assess the effectiveness of treatment with inclisiran (S.C.) in combination with rosuvastatin (P.O), alirocumab (S.C.) in combination with rosuvastatin (P.O) compared to standard rosuvastatin therapy in paediatric population with heterozygous familial hypercholesterolaemia , in terms of: (a) achieving the therapeutic goal of LDL-C <100 mg/dl at 24 weeks (V6) and 60 weeks (V9); b)change in parameters of the extended lipid profile after 24 weeks (V6), 60 weeks (V9) and 104 weeks (V13); (c) changes in CIMT values after 104 weeks of treatment (V13); (d) changes in quality of life of HeFH patients after 24 weeks (V6) and 104 weeks of treatment (V13).

Conditions and MedDRA coding

heterozygous familial hypercholesterolemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Obtain informed written consent for the patient to participate in the study, for genetic testing and for the processing of personal data.
2. Age 10 years-15 years and 6 months.
3. 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.
4. Negative serum pregnancy test (beta-HCG) in menstruating girls.
5. Consent to the use of contraceptive methods as described in the study protocol.

Exclusion criteria 8

1. 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.
2. Fasting triglycerides > 350 mg/d (l>3.95 mmol/l).
3. Uncontrolled hypertension.
4. Chronic kidney disease (eGFR <30 ml/min/1.73m2).
5. 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.
6. LDL - apheresis within the last month prior to inclusion in the study.
7. Use of ‘ prohibited’ drugs (see section 7.2.6 of the protocol for details).
8. Body weight <23kg

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 4

1. 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).
2. 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).
3. Change in CIMT (expressed in mm and z-score) after 104 weeks of treatment (V13) versus baseline measurement (V3).
4. 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).

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Lodz

Sponsor organisation

Medical University Of Lodz

Address

Al. Tadeusza Kosciuszki 4

City

Lodz

Postcode

90-419

Country

Poland

Scientific contact point

Organisation

Medical University Of Lodz

Contact name

Marlena Broncel

Public contact point

Organisation

Medical University Of Lodz

Contact name

Katarzyna Wiklak-Mrowińska

Locations

1 EU/EEA country · 2 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 53 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