Clinical trial • Phase III • Cardiology

INCLISIRAN for Heterozygous familial hypercholesterolemia

Phase III trial of INCLISIRAN for Heterozygous familial hypercholesterolemia.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Heterozygous familial hypercholesterolemia
Trial Stage
Phase III
Drug Modality
Other RNA
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
25-09-2024
First CTIS Authorization Date
04-02-2025

Trial design

Randomised, open-label, active: kjx839 (inclisiran, investigational product). comparator: placebo to kjx839 (inclisiran) 0 mg/1.5 ml solution for injection in vial (placebo). dose and detailed schedule not specified in the available ctis data.-controlled Phase III trial across 36 sites in Netherlands, Italy, Poland and others.

Randomised
Yes
Open Label
Yes
Comparator
Active: KJX839 (inclisiran, investigational product). Comparator: Placebo to KJX839 (Inclisiran) 0 mg/1.5 mL Solution for injection in vial (placebo). Dose and detailed schedule not specified in the available CTIS data.
Target Sample Size
24
Trial Duration For Participant
720

Eligibility

Recruits 24 paediatric patients.

Pregnancy Exclusion
Pregnant or nursing females
Vulnerable Population
The study population comprises children aged 6 to <12 years (vulnerable population). Informed consent is required from the parent/legal guardian; assent is required from children with age-appropriate assent forms (Pre-Adolescent Assent, Child Assent, Adolescent Assent). Country-specific parent/legal guardian ICFs, assent forms, genetics consent and pregnancy follow-up consent documents are provided.

Inclusion criteria

  • {"criterion_text":"- Male or female participants, 6 to <12 years of age at screening"}
  • {"criterion_text":"- HeFH diagnosed either by genetic testing or on phenotypic criteria"}
  • {"criterion_text":"- Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening"}
  • {"criterion_text":"- For participants 8 to <12 years, on an optimal dose of statin (investigator’s discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants <8 years, the use of background lipid-lowering treatment is based on investigator’s discretion."}
  • {"criterion_text":"- Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation."}

Exclusion criteria

  • {"criterion_text":"- Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9"}
  • {"criterion_text":"- Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome"}
  • {"criterion_text":"- Homozygous familial hypercholesterolemia (HoFH)"}
  • {"criterion_text":"- Body weight <16 kg at the screening and/or randomization (Day 1) visit"}
  • {"criterion_text":"- 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)"}
  • {"criterion_text":"- Pregnant or nursing females"}
  • {"criterion_text":"- Recent and/or planned use of other investigational medicinal products or devices"}

Endpoints

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). LDL-C is measured fasting (screening required fasting LDL-C >130 mg/dL) and percent change calculated versus baseline 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 fasting LDL-C measured after Day 90 up to Day 330 (Year 1)."}
  • {"endpoint_text":"- Absolute change in LDL-C from baseline to Day 330 (Year 1)","definition_or_measurement_approach":"Absolute change in fasting LDL-C from baseline to Day 330."}
  • {"endpoint_text":"- Percent change in PCSK9, total cholesterol, Apo B, and non-HDL-C from baseline to Day 330 (Year 1)","definition_or_measurement_approach":"Percent change from baseline to Day 330 for PCSK9, total cholesterol, apolipoprotein B and non-HDL-C (laboratory measurements)."}
  • {"endpoint_text":"- Percent change and absolute change in LDL-C, PCSK9, total cholesterol, Apo B, non-HDL-C, lipoprotein (a) [Lp(a)], triglycerides, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720 (Year 2)","definition_or_measurement_approach":"Percent and absolute changes from baseline to each scheduled assessment up to Day 720 for the listed lipid and biomarker parameters."}
  • {"endpoint_text":"- Incidence, severity and relationship to study drug of treatment-emergent adverse events (AEs) and serious adverse events (SAEs); vital signs; laboratory parameters; anti-drug antibodies (ADA) measurement; growth (height, weight, body mass index (BMI)); pubertal development (sexual hormones and Tanner staging)","definition_or_measurement_approach":"Safety assessments include recording treatment-emergent AEs/SAEs, vital signs, laboratory tests, ADA measurement, growth parameters (height, weight, BMI) and pubertal development (hormone measurements and Tanner staging) through the study period."}

Recruitment

Planned Sample Size
24
Recruitment Window Months
58
Consent Approach
Informed consent is provided by the parent/legal guardian (Parent Legal Guardian ICFs). Age-appropriate assent is obtained using Pre-Adolescent Assent, Child Assent or Adolescent Assent forms as applicable. Separate genetics consent and pregnancy follow-up consent documents are available. Consent/assent documents are provided in country-specific languages (examples in dossier include Dutch, Italian, Polish, Czech, German, Spanish, French, Portuguese, Greek, Hungarian and English).

Geography

Total Number Of Sites
36
Total Number Of Participants
37

Netherlands

Earliest CTIS Part Ii Submission Date
06-01-2025
Latest Decision Or Authorization Date
24-04-2026
Processing Time Days
473
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Amsterdam UMC Stichting
Department Name
3450: Pediatric Metabolic Diseases
Principal Investigator Name
Willemijn Corpeleijn
Principal Investigator Email
w.e.corpeleijn@amsterdamumc.nl
Contact Person Name
Willemijn Corpeleijn
Contact Person Email
w.e.corpeleijn@amsterdamumc.nl

Italy

Earliest CTIS Part Ii Submission Date
23-12-2024
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
491
Number Of Sites
4
Number Of Participants
3

Sites

Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
3801: Centro Dislipidemie
Principal Investigator Name
Giuliana Germana Mombelli
Principal Investigator Email
giuliana.mombelli@ospedaleniguarda.it
Contact Person Name
Giuliana Germana Mombelli
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
3803:Dipartimento Ospedale della Donna e del Bambino
Principal Investigator Name
Claudio Maffeis
Principal Investigator Email
claudio.maffeis@univr.it
Contact Person Name
Claudio Maffeis
Contact Person Email
claudio.maffeis@univr.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
3804: Endocrinologia pediatrica
Principal Investigator Name
Luisa De Sanctis
Principal Investigator Email
luisa.desanctis@unito.it
Contact Person Name
Luisa De Sanctis
Contact Person Email
luisa.desanctis@unito.it
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
3800: U.O.C. Clinical Trial Center
Principal Investigator Name
Paola Sabrina Buonuomo
Principal Investigator Email
psabrina.buonuomo@opbg.net
Contact Person Name
Paola Sabrina Buonuomo
Contact Person Email
psabrina.buonuomo@opbg.net

Poland

Earliest CTIS Part Ii Submission Date
17-01-2025
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
466
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
3501: Klinika Pediatrii, Diabetologii i Endokrynologii
Principal Investigator Name
Małgorzata Myśliwiec
Principal Investigator Email
mysliwiec@gumed.edu.pl
Contact Person Name
Małgorzata Myśliwiec
Contact Person Email
mysliwiec@gumed.edu.pl
Site Name
Uniwersytecki Dzieciecy Szpital Kliniczny Im. L. Zamenhofa W Bialymstoku
Department Name
3502: Klinika Pediatrii, Reumatologii, Immunologii i Chorób Metabolicznych Kości
Principal Investigator Name
Radosław Motkowski
Principal Investigator Email
radoslaw.motkowski@umb.edu.pl
Contact Person Name
Radosław Motkowski
Contact Person Email
radoslaw.motkowski@umb.edu.pl
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
3500: Regionalne Centrum Chorób Rzadkich
Principal Investigator Name
Ewa Starostecka
Principal Investigator Email
ewastarostecka@wp.pl
Contact Person Name
Ewa Starostecka
Contact Person Email
ewastarostecka@wp.pl

Czechia

Earliest CTIS Part Ii Submission Date
23-12-2024
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
490
Number Of Sites
2
Number Of Participants
1

Sites

Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
2950:Klinika pediatrie a dědičných poruch metabolismu
Principal Investigator Name
Jan Jesina
Principal Investigator Email
Pavel.Jesina@vfn.cz
Contact Person Name
Jan Jesina
Contact Person Email
Pavel.Jesina@vfn.cz
Site Name
Fakultni Nemocnice V Motole
Department Name
2951:ULCHKB
Principal Investigator Name
Jana Cepova
Principal Investigator Email
Jana.Cepova@fnmotol.cz
Contact Person Name
Jana Cepova
Contact Person Email
Jana.Cepova@fnmotol.cz

Austria

Earliest CTIS Part Ii Submission Date
10-01-2025
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
473
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH
Department Name
Department of pediatrics and adolescent medicine
Principal Investigator Name
Katharina Moerwald
Principal Investigator Email
k.moerwald@salk.at
Contact Person Name
Katharina Moerwald
Contact Person Email
k.moerwald@salk.at
Site Name
Medical University Of Vienna
Department Name
Department of pediatrics and adolescent medicine
Principal Investigator Name
Susanne Greber-Platzer
Principal Investigator Email
susanne.greber-platzer@meduniwien.ac.at
Contact Person Name
Susanne Greber-Platzer

Spain

Earliest CTIS Part Ii Submission Date
23-12-2024
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
490
Number Of Sites
9
Number Of Participants
9

Sites

Site Name
Hospital Universitario Regional De Malaga
Department Name
3658: Pediatría
Principal Investigator Name
Victor Manuel Navas Lopez
Principal Investigator Email
victor.navas@gmail.com
Contact Person Name
Victor Manuel Navas Lopez
Contact Person Email
victor.navas@gmail.com
Site Name
Hospital General Universitario De Elche
Department Name
3653: Pediatría
Principal Investigator Name
José Pastor Delgado
Principal Investigator Email
pastor_jos@gva.es
Contact Person Name
José Pastor Delgado
Contact Person Email
pastor_jos@gva.es
Site Name
Hospital Universitario De Navarra
Department Name
3655: Pediatría
Principal Investigator Name
Maria Jesús Chueca Guindulain
Principal Investigator Email
mchuecag@cfnavarra.es
Contact Person Name
Maria Jesús Chueca Guindulain
Contact Person Email
mchuecag@cfnavarra.es
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
3657: Pediatría
Principal Investigator Name
Silvia Meavilla Olivas
Principal Investigator Email
silviamaria.meavilla@sjd.es
Contact Person Name
Silvia Meavilla Olivas
Contact Person Email
silviamaria.meavilla@sjd.es
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
3651: Pediatría
Principal Investigator Name
Gemma Carreras González
Principal Investigator Email
GCarreras@santpau.cat
Contact Person Name
Gemma Carreras González
Contact Person Email
GCarreras@santpau.cat
Site Name
Hospital Germans Trias I Pujol
Department Name
3656: Pediatría
Principal Investigator Name
Aina Valls Llussà
Principal Investigator Email
avalls.germanstrias@gencat.cat
Contact Person Name
Aina Valls Llussà
Contact Person Email
avalls.germanstrias@gencat.cat
Site Name
Hospital Universitario Puerta Del Mar
Department Name
3652: Pediatría
Principal Investigator Name
Jesús Domínguez Riscart
Principal Investigator Email
jesus.dominguezriscart@gmail.com
Contact Person Name
Jesús Domínguez Riscart
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
3650: Pediatría
Principal Investigator Name
Emilio José García García
Principal Investigator Email
emilioj.garcia.sspa@juntadeandalucia.es
Contact Person Name
Emilio José García García
Site Name
Hospital Universitario De Navarra (duplicate entry in list)
Department Name
3655: Pediatría
Principal Investigator Name
Maria Jesús Chueca Guindulain
Principal Investigator Email
mchuecag@cfnavarra.es
Contact Person Name
Maria Jesús Chueca Guindulain
Contact Person Email
mchuecag@cfnavarra.es

Belgium

Earliest CTIS Part Ii Submission Date
25-12-2024
Latest Decision Or Authorization Date
24-04-2026
Processing Time Days
485
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
2901 : Paediatrics - Paediatric Hepatology
Principal Investigator Name
Xavier Stephenne
Principal Investigator Email
xavier.stephenne@saintluc.uclouvain.be
Contact Person Name
Xavier Stephenne
Site Name
UZ Leuven
Department Name
2900 : Paediatrics - Metabolic Diseases
Principal Investigator Name
Peter Witters
Principal Investigator Email
Peter.witters@uzleuven.be
Contact Person Name
Peter Witters
Contact Person Email
Peter.witters@uzleuven.be

Hungary

Earliest CTIS Part Ii Submission Date
06-12-2024
Latest Decision Or Authorization Date
29-04-2026
Processing Time Days
509
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
University Of Pecs
Department Name
3301: Gyermekgyogyaszati Klinika
Principal Investigator Name
Decsi Tamas
Principal Investigator Email
decsi.tamas@pte.hu
Contact Person Name
Decsi Tamas
Contact Person Email
decsi.tamas@pte.hu
Site Name
Cortex Study Center
Department Name
3300: Gyermekgyogyaszat
Principal Investigator Name
Szamosi Tamas
Principal Investigator Email
szamosi.tamas@semmelweis.hu
Contact Person Name
Szamosi Tamas
Contact Person Email
szamosi.tamas@semmelweis.hu

Germany

Earliest CTIS Part Ii Submission Date
03-01-2025
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
479
Number Of Sites
3
Number Of Participants
2

Sites

Site Name
Medical Center - University Of Freiburg
Department Name
3153 : Zentrum für Kinder- und Jugendmedizin
Principal Investigator Name
Clemens Kamrath
Principal Investigator Email
clemens.kamrath@uniklinik-freiburg.de
Contact Person Name
Clemens Kamrath
Site Name
Hannoversche Kinderheilanstalt
Department Name
3152 : Diabetologie, Endokrinologie, Gastroenterologie und Klinische Forschung
Principal Investigator Name
Olga Kordonouri
Principal Investigator Email
Kordonouri@hka.de
Contact Person Name
Olga Kordonouri
Contact Person Email
Kordonouri@hka.de
Site Name
Goethe University Frankfurt
Department Name
3150 : Universitaetsklinikum Frankfurt Klinik für Kinder- und Jugendmedizin
Principal Investigator Name
Ulrich Paetow
Principal Investigator Email
paetow@med.uni-frankfurt.de
Contact Person Name
Ulrich Paetow
Contact Person Email
paetow@med.uni-frankfurt.de

France

Earliest CTIS Part Ii Submission Date
08-11-2024
Latest Decision Or Authorization Date
24-04-2026
Processing Time Days
532
Number Of Sites
4
Number Of Participants
2

Sites

Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
3051:ENDOCRINOLOGIE MALADIES METABOLIQUES ET NUTRITION
Principal Investigator Name
Bertrand CARIOU
Principal Investigator Email
Bertrand.Cariou@univ-nantes.fr
Contact Person Name
Bertrand CARIOU
Contact Person Email
Bertrand.Cariou@univ-nantes.fr
Site Name
Centre Hospitalier Universitaire De Nantes (Saint Herblain site)
Department Name
3051:ENDOCRINOLOGIE MALADIES METABOLIQUES ET NUTRITION
Principal Investigator Name
Bertrand CARIOU
Principal Investigator Email
Bertrand.Cariou@univ-nantes.fr
Contact Person Name
Bertrand CARIOU
Contact Person Email
Bertrand.Cariou@univ-nantes.fr
Site Name
Trousseau Hospital
Department Name
3050:GASTRO-ENTERO PEDIATRIQUE
Principal Investigator Name
Julie LEMALE
Principal Investigator Email
julie.lemale@aphp.fr
Contact Person Name
Julie LEMALE
Contact Person Email
julie.lemale@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
3052:HOPITAL LA TIMONE ENFANTS SCE DE PEDIATRIE MULTIDISCIPLINAIRE
Principal Investigator Name
Rachel REYNAUD
Principal Investigator Email
Rachel.REYNAUD@ap-hm.fr
Contact Person Name
Rachel REYNAUD
Contact Person Email
Rachel.REYNAUD@ap-hm.fr

Portugal

Earliest CTIS Part Ii Submission Date
28-11-2024
Latest Decision Or Authorization Date
24-04-2026
Processing Time Days
512
Number Of Sites
4
Number Of Participants
3

Sites

Site Name
Unidade Local De Saude De Santo Antonio E.P.E.
Department Name
3551: Serviço de Pediatria
Principal Investigator Name
Mónica Tavares
Principal Investigator Email
U09412@chporto.min-saude.pt
Contact Person Name
Mónica Tavares
Contact Person Email
U09412@chporto.min-saude.pt
Site Name
Unidade Local De Saude De Santa Maria E.P.E.
Department Name
3550: Serviço de Pediatria
Principal Investigator Name
Rita Isabel Roussado José Jotta de Oliveira
Principal Investigator Email
Rita.oliveira@ulssm.min-saude.pt
Contact Person Name
Rita Isabel Roussado José Jotta de Oliveira
Site Name
Unidade Local De Saude De Coimbra E.P.E.
Department Name
3552: Serviço de Pediatria
Principal Investigator Name
Raquel Soares
Principal Investigator Email
Raquelsoares@ulscoimbra.min-saude.pt
Contact Person Name
Raquel Soares
Site Name
Unidade Local de Saude de Sao Joao E.P.E.
Department Name
3554: Serviço de Pediatria
Principal Investigator Name
Susana Mesquita de Campos Corujeira
Principal Investigator Email
Susanamcorujeira@gmail.com
Contact Person Name
Susana Mesquita de Campos Corujeira
Contact Person Email
Susanamcorujeira@gmail.com

Sponsor

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
Start up CTA role actions
Name
IQVIA Limited
Name
Icon Clinical Research Limited
Name
Syneos Health Inc.
Name
Parexel International (IRL) Limited
Name
Medpace Inc.
Name
WCG Clinical Inc.
Name
Labcorp Pharmaceutical Research And Development (Shanghai) Co. Ltd.
Name
Medpace Laboratories Singapore

Third parties

  • {"country":"Austria","full_name":"ABF Pharmaceutical Services GmbH","duties_or_roles":"Local depot for torage and distribution of AxMP, to sites andDestruction of IMP/AxMP","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"Start up CTA role actions","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Shanghai Xiawei Medical Laboratory Co. Ltd.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Medpace Reference Laboratories China","duties_or_roles":"","organisation_type":"Industry"}
  • {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Labcorp Pharmaceutical Research And Development (Shanghai) Co. Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Singapore","full_name":"Medpace Laboratories Singapore","duties_or_roles":"","organisation_type":"Industry"}
  • {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Simpleshow USA Corp.","duties_or_roles":"Production of patient engagement video material","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Medpace Reference Laboratories China (duplicate entry)","duties_or_roles":"","organisation_type":"Industry"}

Investigational products

Investigational Product Name
INCLISIRAN
Active Substance
INCLISIRAN
Modality
Other RNA
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
600 mg
Investigational Product Name
KJX839
Active Substance
INCLISIRAN
Modality
Other RNA
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
1500 mg
Investigational Product Name
Placebo to KJX839 (Inclisiran) 0 mg/1.5 mL Solution for injection in vial
Modality
Other
Combination Treatment
Yes

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