Ignite Creation Date:
2025-12-26 @ 5:23 PM
Ignite Modification Date:
2025-12-29 @ 12:48 AM
Study NCT ID:
NCT06597006
Status:
RECRUITING
Last Update Posted:
2025-12-12
First Post:
2024-09-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000090542', 'term': 'Homozygous Familial Hypercholesterolemia'}, {'id': 'D006938', 'term': 'Hyperlipoproteinemia Type II'}, {'id': 'D006937', 'term': 'Hypercholesterolemia'}, {'id': 'D006949', 'term': 'Hyperlipidemias'}, {'id': 'D050171', 'term': 'Dyslipidemias'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D001024', 'term': 'Aortic Valve Stenosis'}], 'ancestors': [{'id': 'D008052', 'term': 'Lipid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006951', 'term': 'Hyperlipoproteinemias'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D000082862', 'term': 'Aortic Valve Disease'}, {'id': 'D006349', 'term': 'Heart Valve Diseases'}, {'id': 'D014694', 'term': 'Ventricular Outflow Obstruction'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C585830', 'term': 'ALN-PCS'}, {'id': 'D000077330', 'term': 'Saline Solution'}], 'ancestors': [{'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR'], 'maskingDescription': 'Masked (Year 1) to No Masking (Year 2)'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Parallel (Year 1) to single-group (Year 2)'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 9}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-02-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2029-04-15', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-05', 'studyFirstSubmitDate': '2024-09-11', 'studyFirstSubmitQcDate': '2024-09-11', 'lastUpdatePostDateStruct': {'date': '2025-12-12', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2024-09-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-03-23', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage change in LDL-C from baseline to Day 330 (Year 1)', 'timeFrame': 'Baseline and Day 330', 'description': 'Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \\[percent change\\] at Day 330'}], 'secondaryOutcomes': [{'measure': 'Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)', 'timeFrame': 'Baseline, after Day 90 up to Day 330', 'description': 'Evaluate the effect of inclisiran compared to placebo on reducing LDL-C \\[time-adjusted percent change\\] over Year 1'}, {'measure': 'Percent change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Absolute change in LDL-C, total cholesterol, non-HDL-C, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}, {'measure': 'Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)', 'timeFrame': 'Baseline, up to Day 720', 'description': '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'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Homozygous familial hypercholesterolemia (HoFH),', 'LDL-cholesterol (LDL-C), children, pediatric,', 'small interfering ribonucleic acid (siRNA),', 'inclisiran,', 'Familial Hypercholesterolemia,', 'Homozygous FH,', 'Hypercholesterolemia,', 'Lipoprotein(a),', 'Hyperlipidemia,', 'Dyslipidemia,', 'Cardiovascular Diseases,', 'Heart Failure,', 'Cholesterol,', 'Aortic Stenosis'], 'conditions': ['Familial Hypercholesterolemia - Homozygous']}, 'descriptionModule': {'briefSummary': 'This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to \\<12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).', 'detailedDescription': 'This is a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to \\<12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '11 Years', 'minimumAge': '2 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Male or female participants, 2 to \\<12 years of age at screening\n* HoFH diagnosed by genetic confirmation\n\n \\- Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also exclusion criteria)\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 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.\n\nExclusion Criteria:\n\n* Documented evidence of a null (negative) mutation in both LDLR alleles\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\n* Recent and/or planned use of other investigational medicinal products or devices"}, 'identificationModule': {'nctId': 'NCT06597006', 'acronym': 'ORION-19', 'briefTitle': 'Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children With Homozygous Familial Hypercholesterolemia', 'organization': {'class': 'INDUSTRY', 'fullName': 'Novartis'}, 'officialTitle': 'Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Children (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol', 'orgStudyIdInfo': {'id': 'CKJX839C12304'}, 'secondaryIdInfos': [{'id': '2024-514595-41', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Inclisiran', 'description': 'Year 1 - inclisiran sodium subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium subcutaneous injection (given at Days 450 and 630)', 'interventionNames': ['Drug: Inclisiran']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium subcutaneous injection (given at Days 360, 450, and 630)', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Inclisiran', 'type': 'DRUG', 'otherNames': ['KJX839'], 'description': "Inclisiran (inclisiran sodium 300 mg subcutaneous (s.c.) for participants with body weight ≥23 kg, inclisiran sodium 180 mg s.c. for participants with body weight \\<23 kg to ≥16 kg, or inclisiran sodium 100 mg s.c. for participants with body weight \\<16 kg. The dose level is based on the participant's body weight on Day 1 (for Part 1) and Day 360 (for Part 2), respectively.", 'armGroupLabels': ['Inclisiran']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['saline solution'], 'description': 'Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Luis Gay', 'role': 'CONTACT', 'email': 'Luis.Gay@ucsf.edu', 'phone': '+1 415 990 7296'}, {'name': 'Martin Thelin', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'UC San Francisco Medical Center', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Luis Gay', 'role': 'CONTACT', 'email': 'luis.gay@ucsf.edu', 'phone': '+1 415 476 8338'}, {'name': 'Martin Thelin', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'UC San Francisco Medical Center', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Desiree Tobechukwu Nwanze', 'role': 'CONTACT', 'email': 'dnwanze@childrensnational.org', 'phone': '+1 202 476 5000'}, {'name': 'Sarah Clauss', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Childrens National Hospital', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Jodi Pagano', 'role': 'CONTACT', 'email': 'jpagano@wustl.edu'}, {'name': 'Anne Goldberg', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Washington Univ School Of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '1090', 'city': 'Vienna', 'status': 'RECRUITING', 'country': 'Austria', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': '100013', 'city': 'Beijing', 'state': 'Beijing Municipality', 'status': 'RECRUITING', 'country': 'China', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}, {'zip': '60590', 'city': 'Frankfurt am Main', 'state': 'Hesse', 'status': 'RECRUITING', 'country': 'Germany', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 50.11552, 'lon': 8.68417}}, {'zip': '455 00', 'city': 'Ioannina', 'status': 'RECRUITING', 'country': 'Greece', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 39.66341, 'lon': 20.85187}}, {'zip': '16150', 'city': 'Kota Bharu', 'state': 'Kelantan', 'status': 'RECRUITING', 'country': 'Malaysia', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 6.12361, 'lon': 102.24333}}, {'zip': '1105 AZ', 'city': 'Amsterdam', 'state': 'North Holland', 'status': 'RECRUITING', 'country': 'Netherlands', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}, {'zip': '9301', 'city': 'Bloemfontein', 'state': 'Free State', 'status': 'RECRUITING', 'country': 'South Africa', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': -29.12107, 'lon': 26.214}}, {'zip': '407219', 'city': 'Taichung', 'status': 'RECRUITING', 'country': 'Taiwan', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 24.1469, 'lon': 120.6839}}, {'zip': '111045', 'city': 'Taipei', 'status': 'RECRUITING', 'country': 'Taiwan', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 25.05306, 'lon': 121.52639}}, {'zip': '01330', 'city': 'Adana', 'state': 'Saricam', 'status': 'RECRUITING', 'country': 'Turkey (Türkiye)', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 36.98615, 'lon': 35.32531}}, {'zip': '06500', 'city': 'Ankara', 'state': 'Yenimahalle', 'status': 'RECRUITING', 'country': 'Turkey (Türkiye)', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 39.91987, 'lon': 32.85427}}, {'zip': '35100', 'city': 'Izmir', 'status': 'RECRUITING', 'country': 'Turkey (Türkiye)', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 38.41273, 'lon': 27.13838}}, {'zip': 'SO16 6YD', 'city': 'Southampton', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': 'Novartis Investigative Site', 'geoPoint': {'lat': 50.90395, 'lon': -1.40428}}], 'centralContacts': [{'name': 'Novartis Pharmaceuticals', 'role': 'CONTACT', 'email': 'novartis.email@novartis.com', 'phone': '1-888-669-6682'}, {'name': 'Novartis Pharmaceuticals', 'role': 'CONTACT', 'phone': '+41613241111'}], 'overallOfficials': [{'name': 'Novartis Pharmaceuticals', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Novartis Pharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', '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.\n\nThis trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}