Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06641154
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-11
Brief Title:
Gene Therapy for Crigler Najjar Syndrome Type I
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase III Open Label Study to Evaluate Safety and Efficacy of an Intravenous Injection of GT-UGT1A1-AAV8-02 AAV Vector Expressing the UGT1A1 Transgene in Patients with Crigler-Najjar Syndrome Type I Requiring Phototherapy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 12 multinational open-label study to evaluate the safety and efficacy of an intravenous infusion of GT-UGT1A1-AAV8-02 in patients with Crigler-Najjar type 1 aged 10 years and requiring phototherapy Patients will received a single administration of GT-UGT1A1-AAV8-02 and will be followed for safety and efficacy of approximately 60 months 5 years
a follow-up of approximately 12 months 48 weeks
a long term follow-up of approximately 48 months 4 years in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products released on 22 Oct2009 by the Committee for medicinal products for human use
a follow-up of approximately 12 months 48 weeks
a long term follow-up of approximately 48 months 4 years in order to be in line with the latest EMEA Guideline on follow-up of patients administered with gene therapy medicinal products released on 22 Oct2009 by the Committee for medicinal products for human use
Detailed Description:
Inherited enzymopathy of uridine diphosphate glucuronosyltransferase 1A1 Crigler-Najjar syndrome type I is an orphan disease that arises from loss of function UGT1A1 genetic variants Mutations lead to the enzymes inability in neutralization of bilirubin conjugates Clinically this condition is represented by jaundice and severe neurologic disorders which can lead to death in infancy Diagnosis of Crigler-Najjar syndrome type I is made through biochemical tests and determination the level of unconjugated bilirubin in blood serum as well as by molecular genetic methods There is no specific treatment for the disease except liver transplantation In common clinical practice phototherapy and plasmapheresis are applied in order to reduce serum concentration of unconjugated bilirubin and destroy or eliminate it from the body From the very newborn and further the lifestyle of young patients is dramatically restricted by the long-lasting exposure to phototherapy
In Russian Federation there are just a few children annually with such disorder Under our vision is a girl diagnosed Crigler-Najjar type I who had either opportunity of liver transplantation and long term immunosuppression or receive a gene therapy within previously promising reports in clinics
The Crigler-Najar syndrome is a convenient subject of choice for a gene therapy application because the product of the damaged gene is directly related to a well-studied metabolite in the human body The norms of bilirubin are known to biochemists and it is clear how to study its concentration in plasma In addition the level of bilirubin usually correlates well with the levels of liver enzymes which reflect the condition of the liver and the possible viral load of gene constructs that have liver tropism
Previously successful applications of gene therapy for this syndrome encouraged us to implement this treatment for the first time on children
GT-UGT1A1-AAV8-02 alphaglucuronosyltransferasegene unoparvovec alphacrigen OGP-001 AAV-TBG1A1 is comprised of a recombinant adeno-associated virus type 28 rAAV28 carrying the normal human UGT1A1 gene rAAV28 does not contain viral genes but only viral inverted terminal repeats ITRs that are essential for genome rescue replication packaging and vector persistence Instead of viral genes the vector carries a genetic engineering construct that ensures expression of the human UGT1A1 gene under the control of liver specific promoter of the human thyroxine-binding globulin TBG gene
In Russian Federation there are just a few children annually with such disorder Under our vision is a girl diagnosed Crigler-Najjar type I who had either opportunity of liver transplantation and long term immunosuppression or receive a gene therapy within previously promising reports in clinics
The Crigler-Najar syndrome is a convenient subject of choice for a gene therapy application because the product of the damaged gene is directly related to a well-studied metabolite in the human body The norms of bilirubin are known to biochemists and it is clear how to study its concentration in plasma In addition the level of bilirubin usually correlates well with the levels of liver enzymes which reflect the condition of the liver and the possible viral load of gene constructs that have liver tropism
Previously successful applications of gene therapy for this syndrome encouraged us to implement this treatment for the first time on children
GT-UGT1A1-AAV8-02 alphaglucuronosyltransferasegene unoparvovec alphacrigen OGP-001 AAV-TBG1A1 is comprised of a recombinant adeno-associated virus type 28 rAAV28 carrying the normal human UGT1A1 gene rAAV28 does not contain viral genes but only viral inverted terminal repeats ITRs that are essential for genome rescue replication packaging and vector persistence Instead of viral genes the vector carries a genetic engineering construct that ensures expression of the human UGT1A1 gene under the control of liver specific promoter of the human thyroxine-binding globulin TBG gene
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None