Observational long-term follow- up study for patients previously treated with ex vivo gene therapy
| ISRCTN | ISRCTN91900773 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN91900773 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 1009819 |
| Protocol serial number | Protocol Number 24IC16, CTA Number: 17328/0238/001-0001 |
| Sponsor | Great Ormond Street Hospital for Children NHS Foundation Trust |
| Funder | Great Ormond Street Hospital for Children |
- Submission date
- 08/03/2025
- Registration date
- 11/06/2025
- Last edited
- 10/09/2025
- 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
| Primary study design | Observational |
|---|---|
| Study design | Observational long -term follow-up post gene therapy |
| Secondary study design | Longitudinal study |
| Study type | Participant information sheet |
| 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) |
Approved 14/05/2025, 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 |
| 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(s) |
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: |
| Key secondary outcome measure(s) |
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: |
| Completion date | 30/06/2042 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | All |
| Target sample size at registration | 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 | 01/12/2025 |
| Date of final enrolment | 30/04/2030 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Published as a supplement to the results publication |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
10/09/2025: The following changes were made to the trial record:
1. The date of first enrolment was changed from 01/09/2025 to 01/12/2025.
2. The ethics approval was added.
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.
