Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
3
Countries
1
Sites
1
Crigler-Najjar syndrome
To assess the efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Key facts
- Sponsor
- Genethon
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Trial duration
- 8 Nov 2024 → ongoing
- Decision date (initial)
- 2024-07-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Généthon
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To assess the efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Secondary objectives 6
- To evaluate the safety and tolerability profile of GNT0003
- To evaluate the safety and tolerability profile of imlifidase
- To assess efficacy of imlifidase (cleavage of anti-AAV8 IgG)
- To assess the pharmacokinetic profile of GNT0003
- To assess the pharmacodynamic profile of GNT0003
- To evaluate the impact of GNT0003 in participants’ Quality of Life
Conditions and MedDRA coding
Crigler-Najjar syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10011386 | Crigler-Najjar syndrome | 100000004850 |
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- Not Applicable
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-507007-60-00 | CareCN: A phase I/II, open-label, study to evaluate the safety and efficacy of an intravenous injection of GNT0003 (Adeno-associated Viral Vector expressing the UGT1A1 transgene) in patients with severe Crigler-Najjar syndrome requiring phototherapy | Genethon |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Male or female aged 16 years and older at the time of screening.
- Participant with severe Crigler-Najjar syndrome requiring ≥ 6 hours/ day of phototherapy.
- Participant with molecular confirmation of mutation in the UGT1A1 gene by DNA sequencing.
- Participant with detectable serum neutralizing antibodies against AAV8.
- Participant with laboratory parameters value not clinically significant, as assessed by the investigator, and meeting the following criteria, a. Hematology, 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. Alanine 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).
- 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.
- Signed the study performance informed consent.
- 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 10
- 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.
- 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*
- Participant with significant underlying liver disease.
- Presence of any other clinically significant illness.
- Participant with a history of major thrombotic events, active peripheral vascular disease, or proven hypercoagulable conditions.
- Participant with known hypersensitivity to imlifidase and its excipients.
- Contraindication to corticosteroids, sirolimus, imlifidase, or antihistamines.
- 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
- Participant who underwent liver transplantation
- Participant presents or has a history of thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The proportion of participants with serum total bilirubin ≤ 300 µmol/L, 48 weeks after the GNT0003 infusion and without phototherapy from Week 16
Secondary endpoints 9
- Vital signs, physical examination; Clinically significant abnormalities in safety laboratory assessments; Electrocardiogram (ECG)
- 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.
- Incidence of Adverse Drug Reaction (ADR), malignancies (including liver carcinogenicity) up to 60 months after GNT0003 administration.
- Comparison of total anti-AAV8 IgG in serum before imlifidase infusion (s) versus prior to GNT0003 administration
- Time to GNT0003 vector clearance from blood, urine, saliva, faeces, and semen (for male)
- Change in serum total bilirubin, in serum bilirubin/albumin ratio from baseline to Week 48
- Change in serum total bilirubin, in serum bilirubin/albumin ratio from baseline to 60 months
- Mean time to restart phototherapy
- Change from baseline in health-related quality of life measured by SF-36 after GNT0003 administration
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Idefirix 11 mg powder for concentrate for solution for infusion
PRD8297747 · Product
- Active substance
- Imlifidase
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 0 mg/Kg milligram(s)/kilogram
- Max total dose
- 0 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA41 — -
- Marketing authorisation
- EU/1/20/1471/001
- MA holder
- HANSA BIOPHARMA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD5398875 · Product
- Active substance
- Adeno-Associated Viral Vector Serotype 2/8 Containing the Human UGT1A1 Gene
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 5000000000000 Other
- Max total dose
- 5000000000000 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- GENETHON
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/14/1338
Auxiliary 9
Lidocaine Hydrochloride Monohydrate
SCP101878658 · ATC
- Active substance
- Lidocaine Hydrochloride Monohydrate
- Route of administration
- IV INFUSION
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB04 — METHYLPREDNISOLONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP10330863 · ATC
- Active substance
- Amoxicillin Sodium
- Route of administration
- ORAL
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 0 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA04 — AMOXICILLIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP131338 · ATC
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 Other
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP127887 · ATC
- Active substance
- Pseudoephedrine Hydrochloride
- Substance synonyms
- (1S,2S)-2-METHYLAMINO-1-PHENYL-PROPAN-1-OL HYDROCHLORIDE
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- R06AE07 — CETIRIZINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
J01D · Product
- Pharmaceutical form
- -
- Route of administration
- ORAL
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 0 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01D — OTHER BETA-LACTAM ANTIBACTERIALS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
J01FA · Product
- Pharmaceutical form
- PHF00082MIG
- Route of administration
- IV INFUSION
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 0 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01FA — MACROLIDES
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Betamethasone Sodium Phosphate
SCP1158234 · ATC
- Active substance
- Betamethasone Sodium Phosphate
- Substance synonyms
- BETAMETHASONE DISODIUM PHOSPHATE
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 Other
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP183235 · ATC
- Active substance
- Sirolimus
- Substance synonyms
- SEL-110.36, RAPAMYCIN, NPG-12G, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
- Route of administration
- ORAL
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 4 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AA10 — SIROLIMUS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP128438 · ATC
- Active substance
- Pseudoephedrine Hydrochloride
- Substance synonyms
- (1S,2S)-2-METHYLAMINO-1-PHENYL-PROPAN-1-OL HYDROCHLORIDE
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- R06AX13 — LORATADINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Genethon
- Sponsor organisation
- Genethon
- Address
- 1 Rue De L Internationale
- City
- Evry-Courcouronnes
- Postcode
- 91000
- Country
- France
Scientific contact point
- Organisation
- Genethon
- Contact name
- Clinical Development Department
Public contact point
- Organisation
- Genethon
- Contact name
- Clinical Development Department
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| ICTA Project Management En Abrege ICTA P.M. ORG-100008364
|
Fontaine Les Dijon, France | On site monitoring, Code 12, Other, Code 5, Data management, Code 8 |
| Mde Services Group Limited ORG-100043621
|
Bracknell, United Kingdom | Other |
| Genosafe S.A.S. ORG-100013179
|
Evry Cedex, France | Laboratory analysis |
| Hansa Biopharma AB ORG-100006732
|
Lund, Sweden | Laboratory analysis |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 3 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-11-08 | 2024-11-08 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 37 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-510405-18_ForPub | 6.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Diary_additional phototherapy_16-17 years_FR | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Diary_additional phototherapy_EN | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Diary_additional phototherapy_FR | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_after week 24_16-17 years_FR_ForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_after week 24_EN_MemoForPub | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_after week 24_FR_MemoForPub | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_corticoids after week 7_EN_MemoForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_corticoids after week 7_FR_MemoForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_corticoids after week 9_16-17 years_FR_ForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_Corticoids after week 9_EN_MemoForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_Corticoids after week 9_FR_MemoForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_until week 24_16-17 years_FR_ForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_until week 24_EN_MemoForPub | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Drug Diary_until week 24_FR_MemoForPub | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Phototherapy quality of sleep DIARY_before GNT0003 infusion_EN | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Phototherapy quality of sleep DIARY_before GNT0003 infusion_FR | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Phototherapy quality of sleep DIARY_post GNT0003 infusion_EN | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_Patient Phototherapy quality of sleep DIARY_post GNT0003 infusion_FR | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_PT and Qof sleep DIARY_post GNT0003 infusion_16-17 years_FR | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_PT and QofSleep Diary_before GNT0003 infusion_16-17 years_FR | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire PedsQL_13-18_EN_ForPub | 4.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire PedsQL_13-18_FR_ForPub | 4.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire PedsQL_Parent_EN_ForPub | 4.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire PedsQL_Parent_FR_ForPub | 4.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire SF-36V2_EN_MemoForPub | 1.0 |
| Protocol (for publication) | D4_Patient facing documents_Questionnaire SF-36V2_FR_MemoForPub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_16-17_ForPub | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_ForPub | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Parents_ForPub | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Patient fees Reimbursement_ForPub | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnancy | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Previous minor_ForPub | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Imlifidase | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis Short_EN_2023-510405-18_ForPub | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis Short_FR_2023-510405-18_ForPub | 5.0 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-26 | France | Acceptable with conditions 2024-07-17
|
2024-07-17 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-13 | France | Acceptable 2024-08-21
|
2024-08-21 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-10-03 | France | Acceptable 2024-08-21
|
2024-10-03 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-01-21 | France | Acceptable 2024-08-21
|
2025-01-21 |
| 5 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-14 | France | Acceptable 2025-05-04
|
2025-05-09 |
| 6 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-07-03 | France | Acceptable 2025-08-13
|
2025-08-20 |
| 7 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-10-03 | France | Acceptable 2025-11-14
|
2025-11-19 |