IMLIFIDASE for Crigler-Najjar syndrome

Inclusion criteria

• {"criterion_text":"- Male or female aged 16 years and older at the time of screening."}
• {"criterion_text":"- Participant with severe Crigler-Najjar syndrome requiring ≥ 6 hours/ day of phototherapy."}
• {"criterion_text":"- Participant with molecular confirmation of mutation in the UGT1A1 gene by DNA sequencing."}
• {"criterion_text":"- Participant with detectable serum neutralizing antibodies against AAV8."}
• {"criterion_text":"- Participant with laboratory parameters value not clinically significant, as assessed by the investigator, and meeting the following criteria, a.\tHematology, clinical chemistry and coagulation ≤ grade 1 (as per Common Terminology Criteria for Adverse Events [CTCAE] criteria) (including but not limited to: activated partial thromboplastin time ≤1.5 x ULN, creatinine increased ≤1.5 x ULN, Platelet count decreased ≥75,000/mm3, lymphocyte count increased ≤20 000/mm3). b.\tAlanine amino-transferase (ALT), aspartate amino-transferase (AST), gamma-glutamyl transferase (GGT) ≤ grade 3 (as per CTCAE criteria: GGT, ALT and/or AST ≤20.0 x ULN if baseline was normal; ≤20.0 x baseline if baseline was abnormal)."}
• {"criterion_text":"- Participants must agree to use a highly effective method of contraception from screening visit (V1) to at least 48 weeks after start of IMP administration."}
• {"criterion_text":"- Signed the study performance informed consent."}
• {"criterion_text":"- Capable of giving signed informed consent (of GNT-018-IDES clinical trial and GNT-018-IDES-PS performance study) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}

Exclusion criteria

• {"criterion_text":"- Participation in another interventional trial during this clinical trial, including investigational trial involving gene or cell therapeutics within 6 months prior to start of IMP administration and during the whole clinical trial; participation in non-interventional registries or epidemiological studies is allowed."}
• {"criterion_text":"- Participant presents or has a history of thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP"}
• {"criterion_text":"- Fibrosis score ≥ 3 (METAVIR) or 10 kPa based on: a)Fibrotest: performed within 12 months prior to screening visit 1* Or b)FibroScan®: performed within 12 months prior to screening visit 1* Or c)Liver biopsy taken within 24 months prior to screening visit 1*"}
• {"criterion_text":"- Participant with significant underlying liver disease."}
• {"criterion_text":"- Presence of any other clinically significant illness."}
• {"criterion_text":"- Participant with a history of major thrombotic events, active peripheral vascular disease, or proven hypercoagulable conditions."}
• {"criterion_text":"- Participant with known hypersensitivity to imlifidase and its excipients."}
• {"criterion_text":"- Contraindication to corticosteroids, sirolimus, imlifidase, or antihistamines."}
• {"criterion_text":"- Treatment with any of the prior/concomitant therapies according to the time frames specified in the protocol. At any time : Gene therapy, Cell based therapy (e.g., stem cell transplantation), CRISPR/Cas9, or any other form of gene editing, imlifidase"}
• {"criterion_text":"- Participant who underwent liver transplantation"}

Primary endpoints

• {"endpoint_text":"- The proportion of participants with serum total bilirubin ≤ 300 µmol/L, 48 weeks after the GNT0003 infusion and without phototherapy from Week 16","definition_or_measurement_approach":"Proportion of participants meeting serum total bilirubin ≤ 300 µmol/L at Week 48 post-GNT0003 infusion, with the requirement that participants have been without phototherapy from Week 16; measured by serum total bilirubin laboratory testing at scheduled visits (assessment at Week 48)."}

Secondary endpoints

• {"endpoint_text":"- Vital signs, physical examination; Clinically significant abnormalities in safety laboratory assessments; Electrocardiogram (ECG)","definition_or_measurement_approach":"Safety assessments by clinical evaluation: vital signs, physical exam, laboratory safety tests and ECGs at scheduled visits; reporting of clinically significant abnormalities."}
• {"endpoint_text":"- Incidence of all treatment-emergent adverse events (TEAE), serious adverse events (SAE), adverse events of special interest (AESI) from imlifidase administration to 48 weeks after GNT0003 infusion.","definition_or_measurement_approach":"AE monitoring and coding (TEAEs, SAEs, AESIs) from imlifidase administration through 48 weeks after GNT0003 infusion according to protocol-specified reporting procedures and CTCAE where applicable."}
• {"endpoint_text":"- Incidence of Adverse Drug Reaction (ADR), malignancies (including liver carcinogenicity) up to 60 months after GNT0003 administration.","definition_or_measurement_approach":"Long-term safety monitoring for ADRs and new malignancies, including liver cancer, up to 60 months post-administration via scheduled follow-up, medical records and AE reporting."}
• {"endpoint_text":"- Comparison of total anti-AAV8 IgG in serum before imlifidase infusion (s) versus prior to GNT0003 administration","definition_or_measurement_approach":"Serologic measurement of total anti-AAV8 IgG levels pre-imlifidase infusion and prior to GNT0003 administration to assess change/cleavage of antibodies."}
• {"endpoint_text":"- Time to GNT0003 vector clearance from blood, urine, saliva, faeces, and semen (for male)","definition_or_measurement_approach":"Measurement of vector presence (e.g., PCR) in blood, urine, saliva, feces, and semen at scheduled time points to determine time to undetectable vector levels."}
• {"endpoint_text":"- Change in serum total bilirubin, in serum bilirubin/albumin ratio from baseline to Week 48","definition_or_measurement_approach":"Laboratory measurement of serum total bilirubin and albumin at baseline and Week 48; calculation of absolute and relative changes and bilirubin/albumin ratio."}
• {"endpoint_text":"- Change in serum total bilirubin, in serum bilirubin/albumin ratio from baseline to 60 months","definition_or_measurement_approach":"Long-term laboratory monitoring of serum total bilirubin and bilirubin/albumin ratio from baseline to Month 60."}
• {"endpoint_text":"- Mean time to restart phototherapy","definition_or_measurement_approach":"Time from GNT0003 administration to the date of restart of phototherapy recorded for each participant; mean time computed across participants."}
• {"endpoint_text":"- Change from baseline in health-related quality of life measured by SF-36 after GNT0003 administration","definition_or_measurement_approach":"Health-related quality of life assessed using the SF-36 questionnaire at baseline and post-administration visits; change from baseline analyzed according to SF-36 scoring rules."}

France

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

19-11-2025

Processing Time Days

540

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Genethon

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"ICTA Project Management En Abrege ICTA P.M.","duties_or_roles":"Sponsor duties codes: 1, 12, 15 (site financial agreement), 5, 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"Patient organization and reimbursement (sponsor duty code 15)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Genosafe S.A.S.","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Hansa Biopharma AB","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Pharmaceutical company"}