Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06518005
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-18
Brief Title:
Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
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:
Clinical trial rationale
CNS is an ultra-rare 11 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
Reduction of UCB is managed with phenobarbital in mild CNS and daily phototherapy in severe CNS
There is no authorized curative medical treatment for CNS Liver transplantation is currently the only curative treatment for severe CNS
GNT0003 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
Imlifidase IgG-degrading enzyme has demonstrated its efficacy in highly sensitized adult kidney transplant patients
To 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
Primary 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
Secondary 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
The trial will include 3 parts
A baseline period for at least 3 months
A treatment period
A follow-up period
Initial post-treatment follow-up over 48 weeks
Long-term follow-up for 4 additional years
This 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
CNS is an ultra-rare 11 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
Reduction of UCB is managed with phenobarbital in mild CNS and daily phototherapy in severe CNS
There is no authorized curative medical treatment for CNS Liver transplantation is currently the only curative treatment for severe CNS
GNT0003 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
Imlifidase IgG-degrading enzyme has demonstrated its efficacy in highly sensitized adult kidney transplant patients
To 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
Primary 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
Secondary 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
The trial will include 3 parts
A baseline period for at least 3 months
A treatment period
A follow-up period
Initial post-treatment follow-up over 48 weeks
Long-term follow-up for 4 additional years
This 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
Detailed Description:
None
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