Ignite Creation Date:
2025-12-25 @ 3:25 AM
Ignite Modification Date:
2026-02-28 @ 4:06 AM
Study NCT ID:
NCT06518005
Status:
RECRUITING
Last Update Posted:
2024-12-03
First Post:
2024-07-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003414', 'term': 'Crigler-Najjar Syndrome'}], 'ancestors': [{'id': 'D006933', 'term': 'Hyperbilirubinemia, Hereditary'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C442815', 'term': 'Mac-1-like protein, Streptococcus'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 3}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-11-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-07', 'completionDateStruct': {'date': '2030-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-11-28', 'studyFirstSubmitDate': '2024-07-18', 'studyFirstSubmitQcDate': '2024-07-23', 'lastUpdatePostDateStruct': {'date': '2024-12-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-07-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-09-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Proportion of participants with serum total bilirubin ≤ 300 μmol/L, 48 weeks after GNT0003 infusion and without phototherapy from Week 16', 'timeFrame': '48 weeks post GNT0003 administration', 'description': 'Decrease of serum total bilirubin level after interruption of daily phototherapy; change in serum total bilirubin from baseline to week 48.'}], 'secondaryOutcomes': [{'measure': 'Incidence of significant clinical and/or laboratoy abnormalities, of all treatment-emergent adverse events, serious adverse events, adverse events of special interrests, adverse drug reactions, malignancies', 'timeFrame': '48 weeks; 60 months', 'description': 'Incidence and severity for each body system and laboratory parameter will be presented and summarized overall'}, {'measure': 'Change in Health-related quality of Life form baseline to week 48 post GNT0003 administration', 'timeFrame': '48 weks', 'description': 'Scale 36-Item Short From Survey (SF-36 Health Survey); from 0 (negative) to 100 (positive)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Crigler-Najjar Syndrome']}, 'descriptionModule': {'briefSummary': "Clinical trial rationale:\n\nCNS is an ultra-rare (\\<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB).\n\nReduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS.\n\nThere is no authorized curative medical treatment for CNS. Liver transplantation is currently the only curative treatment for severe CNS.\n\nGNT0003 is a genetically modified recombinant (r) viral vector composed of the AAV8 viral capsid carrying the UGT1A1 transgene which aims to correct the dysfunction of the mutated gene by achieving durable expression of a functional copy of the affected gene.\n\nImlifidase (IgG-degrading enzyme) has demonstrated its efficacy in highly sensitized adult kidney transplant patients.\n\nTo give participants with pre-existing anti-AAV8 antibodies access to gene therapy treatments, this trial aims to demonstrate the safety and efficacy of GNT0003 following imlifidase pre-treatment in adult participants with severe CNS requiring daily phototherapy and presenting with pre-existing anti-AAV8 antibodies.\n\nPrimary objective: to assess efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies\n\nSecondary objective: to collect data on safety and tolerability of GNT0003 and imlifidase, efficacy of imlifidase, pharmacokinetic and pharmacodynamic profile of GNT0003, and Quality of Life.\n\nThe trial will include 3 parts:\n\n* A baseline period for at least 3 months\n* A treatment period\n* A follow-up period:\n\n * Initial post-treatment follow-up over 48 weeks\n * Long-term follow-up for 4 additional years\n\nThis trial will be conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Participants must be consented using the approved Informed Consent Form before any procedures specified in the protocol are performed."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Main Inclusion Criteria:\n\n1. Severe Crigler-Najjar syndrome requiring ≥ 6 hours/ day of phototherapy\n2. Molecular confirmation of mutation in the UGT1A1gene by DNA sequencing\n3. Detectable serum neutralizing antibodies against AAV8\n4. Laboratory parameters value not clinically significant\n5. Highly effective method of contraception\n6. Affiliated to or a beneficiary of a health care system\n\nExclusion Criteria:\n\n1. Participation in another interventional trial within 6 months prior to start of clinical trial intervention and during the whole clinical trial\n2. Fibrosis score ≥ 3 (METAVIR) or 10 kPa (FibroScan®)\n3. Liver transplantation\n4. Significant underlying liver disease, chronic hepatitis B, C and/or infected with Human immunodeficiency virus\n5. Any other clinically significant illness\n6. Uncontrolled hyperlipidemia.\n7. History of major thrombotic events, active peripheral vascular disease, proven hypercoagulable conditions,\n8. History or presence of thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP\n9. Prior or current treatment with Gene therapy, cell based therapy, CRISPR/Cas9 or any other form of gene editing, imlifidase'}, 'identificationModule': {'nctId': 'NCT06518005', 'briefTitle': 'Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome', 'organization': {'class': 'OTHER', 'fullName': 'Genethon'}, 'officialTitle': 'An Open-label, Phase 2 Trial to Evaluate the Efficacy and Safety of a Single Intravenous Administration of GNT0003 (an Adeno-associated Viral (AAV) Vector Expressing the UGT1A1 Transgene) Following Imlifidase Pre-treatment in Adult Participants With Severe Crigler-Najjar Syndrome (CNS) Requiring Daily Phototherapy and Presenting Pre-existing Anti-AAV8 Antibodies', 'orgStudyIdInfo': {'id': 'GNT-018-IDES'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment with imlifidase', 'description': 'Each participant will be treated with imlifidase', 'interventionNames': ['Drug: Imlifidase']}, {'type': 'EXPERIMENTAL', 'label': 'Treatment with GNT0003', 'description': 'Each participant will be treated with GNT0003', 'interventionNames': ['Drug: GNT0003']}], 'interventions': [{'name': 'Imlifidase', 'type': 'DRUG', 'description': 'Imlifidase: single administration (dose is confidential), Lyophilized powder for concentrate for solution for infusion', 'armGroupLabels': ['Treatment with imlifidase']}, {'name': 'GNT0003', 'type': 'DRUG', 'description': 'GNT0003: single administration 5E+12 VG/kg, Sterile concentrate for solution for infusion', 'armGroupLabels': ['Treatment with GNT0003']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92141', 'city': 'Clamart', 'status': 'RECRUITING', 'country': 'France', 'contacts': [{'role': 'CONTACT', 'email': 'philippe.labrune@abc.aphp.fr', 'phone': '00 33 (0)1 45 37 42 72'}, {'name': 'Philippe LABRUNE, MD,PHD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Hopital Antoine BECLERE', 'geoPoint': {'lat': 48.80299, 'lon': 2.26692}}], 'centralContacts': [{'name': 'GENETHON Clinical Development Department', 'role': 'CONTACT', 'email': 'clinicaldevelopment@genethon.fr', 'phone': '+33 (0) 1 69 47 10 32'}], 'overallOfficials': [{'name': 'Philippe LABRUNE, MD, PHD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'APHP_Hopital Antoine BECLERE'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Genethon', 'class': 'OTHER'}, 'collaborators': [{'name': 'Hansa Biopharma AB', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}