Ignite Creation Date:
2024-05-06 @ 6:26 PM
Last Modification Date:
2024-10-26 @ 2:48 PM
Study NCT ID:
NCT05665166
Status:
RECRUITING
Last Update Posted:
2023-10-12
First Post:
2022-12-07
Brief Title:
Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type II
Sponsor:
University of Manchester
Organization:
University of Manchester
Study Overview
Official Title:
A Phase I-II Study of Cryopreserved Autologous CD34 Haematopoietic Stem Cells Transduced Ex Vivo with CD11b Lentiviral Vector Encoding Human IDS Tagged with ApoEII in Patients with Neuronopathic Mucopolysaccharidosis Type II nMPS II Hunters Syndrome
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
MPS II is a genetic disorder that affects boys Boys with MPS II are missing a working enzyme known as iduronate-2-sulfatase IDS which is needed to break down long sugar chains in the body When this enzyme is missing these sugars build up to excess causing damage and stop organs such as the brain from working properly Children with MPS II often have progressive symptoms such as developmental delay and physical problems
The only approved treatment for MPS II is enzyme replacement therapy This involves a regular infusion of the missing enzyme into the blood stream But this treatment only helps some symptoms and cannot help problems in the brain
This study will be the first in human clinical trial to check whether using a gene therapy in children with MPS II is safe and is able to provide enough enzyme to help with disease symptoms Gene therapy involves changing the genetic information that makes up a person by taking a correct version of the gene that is needed to make the working IDS enzyme and putting it back into the body This means that the body can then make the missing enzyme itself The good thing with this therapy is that the body should be able to make this enzyme forever
To make sure the therapy is safe and working patients will be closely followed for 2 years
The only approved treatment for MPS II is enzyme replacement therapy This involves a regular infusion of the missing enzyme into the blood stream But this treatment only helps some symptoms and cannot help problems in the brain
This study will be the first in human clinical trial to check whether using a gene therapy in children with MPS II is safe and is able to provide enough enzyme to help with disease symptoms Gene therapy involves changing the genetic information that makes up a person by taking a correct version of the gene that is needed to make the working IDS enzyme and putting it back into the body This means that the body can then make the missing enzyme itself The good thing with this therapy is that the body should be able to make this enzyme forever
To make sure the therapy is safe and working patients will be closely followed for 2 years
Detailed Description:
Mucopolysaccharidosis type II MPSII Hunter Syndrome is a rare paediatric X-linked lysosomal storage disease caused by a deficiency in iduronate-2-sulphatase IDS due to a mutation on the IDS gene IDS is essential for the breakdown of the sugar glycosaminoglycans GAGs in particular heparan sulphate HS and dermatan sulphate DS Without this enzyme these sugars accumulate in cells causing damage
Currently enzyme replacement therapy ERT is the only clinically approved treatment available for MPSII However ERT is a supportive therapy and is intended to alleviate symptoms and improve patient quality of life rather than addressing the pathogenic mechanisms of the disease To date there is no effective disease-modifying treatment
This study aims to recruit 5 patients with MPS II who satisfy the inclusion and exclusion criteria and provide full consent between 3 months and 22 months of age at screening The investigational medicinal product IMP will be a cell-based gene therapy that uses genetically modified autologous CD34 haematopoietic stem cells transduced with a lentiviral vector containing the human IDS gene tagged with ApoEII Patients will be followed up for a minimum of 2 years after gene therapy
The therapy works by adding the gene therapy to cells taken from the childs body The cells are then frozen and tested for safety before being given back to the child To collect the cells we will give the child some medicine to mobilize hematopoietic stem cells HSC from their bone marrow into the blood which can then be easily collected A working copy of the IDS gene is then placed into these cells in the laboratory ex vivo The modified HSCs are then given back to the child via a blood infusion where they can travel to and live in the bone marrow In the bone marrow compartment these cells will produce new blood cells that can make the IDS enzyme and can carry it around the whole body including to the brain This means the excess sugar chains can be broken down which may help cells to function normally We think this will reduce MPS II symptoms and may help to prevent damage to the brain
To make sure the therapy is safe patients will be closely followed for 2 years within this trial Additional follow up for a minimum 15 years post therapy or as per current guidance will then be offered
Currently enzyme replacement therapy ERT is the only clinically approved treatment available for MPSII However ERT is a supportive therapy and is intended to alleviate symptoms and improve patient quality of life rather than addressing the pathogenic mechanisms of the disease To date there is no effective disease-modifying treatment
This study aims to recruit 5 patients with MPS II who satisfy the inclusion and exclusion criteria and provide full consent between 3 months and 22 months of age at screening The investigational medicinal product IMP will be a cell-based gene therapy that uses genetically modified autologous CD34 haematopoietic stem cells transduced with a lentiviral vector containing the human IDS gene tagged with ApoEII Patients will be followed up for a minimum of 2 years after gene therapy
The therapy works by adding the gene therapy to cells taken from the childs body The cells are then frozen and tested for safety before being given back to the child To collect the cells we will give the child some medicine to mobilize hematopoietic stem cells HSC from their bone marrow into the blood which can then be easily collected A working copy of the IDS gene is then placed into these cells in the laboratory ex vivo The modified HSCs are then given back to the child via a blood infusion where they can travel to and live in the bone marrow In the bone marrow compartment these cells will produce new blood cells that can make the IDS enzyme and can carry it around the whole body including to the brain This means the excess sugar chains can be broken down which may help cells to function normally We think this will reduce MPS II symptoms and may help to prevent damage to the brain
To make sure the therapy is safe patients will be closely followed for 2 years within this trial Additional follow up for a minimum 15 years post therapy or as per current guidance will then be offered
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2021-000400-38 | EUDRACT_NUMBER | None | None |