Observational long-term follow- up study for patients previously treated with ex vivo gene therapy
| ISRCTN | ISRCTN91900773 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN91900773 |
| IRAS number | 1009819 |
| Secondary identifying numbers | Protocol Number 24IC16, CTA Number: 17328/0238/001-0001 |
- Submission date
- 08/03/2025
- Registration date
- 11/06/2025
- Last edited
- 11/06/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Genetic Diseases
Plain English summary of protocol
Background and study aims
Great Ormond Street Hospital (GOSH) is running clinical trials to test new gene therapies for children with inherited immune system conditions like Chronic Granulomatous Disease and Severe Combined Immunodeficiency. These conditions make it hard for the body to fight infections. The gene therapy works by correcting the faulty gene in the patient’s own blood stem cells and returning them to the body to help rebuild the immune system.
After receiving gene therapy, patients are monitored for 2 to 3 years. However, to make sure the treatment is safe in the long term, patients need to be followed for up to 15 years. This study helps GOSH meet that requirement by continuing to monitor patients for any long-term side effects and to see how well the treatment is working over time.
Who can participate?
Patients can take part if they:
-Received gene therapy as part of a GOSH clinical trial.
-Were treated with gene therapy at GOSH through compassionate use (outside of a trial).
-Were in a commercial follow-up study at GOSH that has since ended.
What does the study involve?
Participants will continue with their usual medical care and follow-up appointments at GOSH. The study mainly involves reviewing medical records and collecting information from routine check-ups. In some cases, extra blood samples may be taken. Rarely, a bone marrow sample might be needed, but this would be discussed in advance.
What are the possible benefits and risks of participating?
There are no direct benefits to the patient, as this study is for monitoring purposes only. However, participation will:
• Help doctors better understand the long-term safety of gene therapy.
• Allow for early detection of any potential issues, ensuring the best possible care for patients.
• Contribute to future improvements in gene therapy, benefiting other patients with similar conditions.
Because this study follows patients over many years, it provides valuable information to help researchers and doctors develop safer and more effective gene therapies for the future.
This study involves minimal risk, as it mainly consists of reviewing existing medical records and routine check-ups. Blood tests may cause mild pain or bruising, but a numbing cream can be used to reduce discomfort. There is also a small chance of minor bleeding or infection, though these risks are uncommon. If any side effects occur, they will be treated appropriately.
Where is the study run from?
Great Ormond Street Hospital (GOSH) (UK)
When is the study starting and how long is it expected to run for?
March 2025 To June 2042
Who is funding the study?
Great Ormond Street Hospital (GOSH) (UK)
Who is the main contact?
Hannah.Badham@gosh.nhs.uk
c.booth@ucl.ac.uk
Contact information
Public
30 Guilford Street
London
WC1N 1EH
United Kingdom
| Phone | +44 20 74059200 |
|---|---|
| hannah.badham@gosh.nhs.uk |
Scientific, Principal Investigator
Great Ormond Street
London
WC1N 3JH
United Kingdom
| Phone | +44 2079052198 |
|---|---|
| c.booth@ucl.ac.uk |
Study information
| Study design | Observational, long -term follow-up post gene therapy |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | Long term follow-up for patients with inborn errors of immunity treated with autologous ex vivo gene modified CD34+ advanced therapies at Great Ormond Street Hospital |
| Study objectives | Primary objective: To characterize the long-term safety of the gene therapy treatment and detect potential gene therapy-related adverse events in participants who received an autologous ex vivo gene modified CD34+ advanced therapy at GOSH. Secondary objective: To evaluate long-term, sustained disease correction and clinical efficacy of the gene therapy treatment through collection of ‘standard of care’ assessment data. |
| Ethics approval(s) |
Submitted 21/03/2025, London - West London & GTAC Research Ethics Committee (2 Redman Place, Stratford, London, NG1 6FS, United Kingdom; +44 2071048075; westlondon.rec@hra.nhs.uk), ref: 25/LO/0188 |
| Health condition(s) or problem(s) studied | Medical condition: X-linked SCID (SCID-X1); p47 deficient Autosomal Recessive Chronic Granulomatous Disease (AR-CGD) and Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID) |
| Intervention | Patients will continue to receive routine medical care and follow-up appointments at GOSH, just as they normally would. This study will involve reviewing medical records and collecting information from standard medical check-ups. In some cases, additional blood samples may be taken. If needed, a bone marrow sample may be collected, but this would only happen in rare cases and would be discussed in advance with the patient and their family. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Cryopreserved lentiviral vector transduced patient CD34+ cells [G2SCID lentiviral vector transduced patient CD34+ cells, CD34+ cells transduced with pCCLChimp47, CD34+ HSCs transduced ex vivo with EFS LV] |
| Primary outcome measure | Characterize the long-term safety of the gene therapy treatment and detect potential gene therapy-related adverse events in participants who received an autologous ex vivo gene modified CD34+ advanced therapy at GOSH. Monitoring will be performed during yearly visit from Year 3 or 4 to Year 15 post-infusion and will include documentation of the: 1. Adverse events (AEs), serious adverse events (SAEs), and/or adverse reactions are measured through clinical assessments and review of medical records. 2. Overall survival (OS) and event-free survival (EFS) are assessed through clinical review of survival status and defined clinical events (rescue HSCT, second gene therapy, mutagenic therapy exposure). 3. Vector copy number (VCN) in peripheral blood cell lineages, measured using quantitative PCR (qPCR). |
| Secondary outcome measures | Evaluate long-term, sustained disease correction and clinical efficacy of the gene therapy treatment through collection of ‘standard of care’ assessment data. Monitoring will be performed during yearly visit from Year 3 or 4 to Year 15 post-infusion and will include documentation of the: 1. Immune reconstitution, measured via laboratory assessments of blood cell counts, lymphocyte subsets (absolute numbers and percentages), and immunoglobulin levels. 2. Discontinuation of immunoglobulin replacement therapy, assessed through review of treatment records and time to discontinuation. |
| Overall study start date | 06/03/2025 |
| Completion date | 30/06/2042 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 70 |
| Key inclusion criteria | 1. Participants must have previously received a CD34+ ATIMP through a clinical trial or compassionate use program at GOSH. 2. The patient displays persistent detectable gene marking. 3. The patient is not followed-up on another LTFU study for the same condition. 4. The patient or their guardian can provide informed consent. 5. Inclusion can be prospective or retrospective. |
| Key exclusion criteria | Refusal to sign informed consent |
| Date of first enrolment | 01/09/2025 |
| Date of final enrolment | 30/04/2030 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Hospital/treatment centre
30 Guilford Street
London
WC1N1EH
England
United Kingdom
| Phone | +44 20 7905 2700 |
|---|---|
| Research.Governance@gosh.nhs.uk | |
| Website | http://www.gosh.nhs.uk/ |
"ROR" |
https://ror.org/03zydm450 |
Funders
Funder type
Hospital/treatment centre
Government organisation / Local government
- Alternative name(s)
- GOSH
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2036 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Submission to regulatory authorities The trial will comply with the Data Protection Act. If Patient, parents/guardian consent, anonymised data may be used for research and development including under commercial agreements reached by the hospital. The people who analyse the information will not be able to identify the subject and will not be able to find out the name, NHS number or contact details. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Editorial Notes
15/05/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 15/05/2025.
10/03/2025: Trial's existence confirmed by NHS HRA.
