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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04797260




Registration number
NCT04797260
Ethics application status
Date submitted
11/03/2021
Date registered
15/03/2021
Date last updated
18/04/2024

Titles & IDs
Public title
Phase I/II Clinical Trial Stem Cell Gene Therapy in RAG1-Deficient SCID
Scientific title
Phase I/II Clinical Trial of Autologous Hematopoietic Stem Cell Gene Therapy in RAG1-Deficient Severe Combined Immunodeficiency
Secondary ID [1] 0 0
L20.067
Universal Trial Number (UTN)
Trial acronym
RAG1-SCID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Combined Immunodeficiency Due to RAG1 Deficiency 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Gene therapy

Experimental: Gene therapy - In this arm, 10 patients will be included for gene therarpy


Treatment: Other: Gene therapy
Patients will be infused with autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (RAG1 LV CD34+ cells).
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Feasibility of successful generation of RAG1 LV CD34+ cells
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
Safety of RAG1 lentiviral gene therapy
Timepoint [2] 0 0
2 years
Secondary outcome [1] 0 0
T cell reconstitution
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Thymic function
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
T and B cell receptor repertoire
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Immunoglobulin dependence
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Persistence of gene marking
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Occurrence of Infections
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Failure to thrive
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Quality of life
Timepoint [8] 0 0
2 years

Eligibility
Key inclusion criteria
1. RAG1-deficient SCID as confirmed by genetic analysis
2. Peripheral blood T cells < 300/µL and/or naïve T cells < 1/µL
3. Age < 2 years
4. Age at least 8 weeks by the time of busulfan and fludarabine administration
5. Lack of an available HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
6. Signed informed consent (parental or guardian)
7. Able to return to the study centre for follow-up (per protocol) during the 2-year study and the 15-year long-term off study review
Minimum age
8 Weeks
Maximum age
24 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Availability of an HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
2. RAG1 deficiency with peripheral blood T cells > 300/µL and/or naïve T cells > 1/µL
3. Omenn syndrome
4. Previous allogeneic HSCT
5. Significant organ dysfunction/co-morbidity (including but not limited to the ones listed below):

1. Mechanical ventilation
2. Shortening fraction on echocardiogram <25%
3. Renal failure defined as dialysis dependence
4. Uncontrolled seizure disorder
6. Any other condition that the investigator considers is a contraindication to collection and/or infusion of trans-duced cells for that individual or indicate patient's inability to follow the protocol, for example contraindication f to busulfan, major congenital abnormalities, ineligible to receive anaesthesia, or documented refusal or inability of the family to return for scheduled visits.
7. Human immunodeficiency virus (HIV) infection or Human T-cell Leukemia Virus (HTLV) infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Childrens Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Italy
State/province [1] 0 0
Roma
Country [2] 0 0
Netherlands
State/province [2] 0 0
Leiden
Country [3] 0 0
Poland
State/province [3] 0 0
Wroclaw
Country [4] 0 0
Spain
State/province [4] 0 0
Barcelona
Country [5] 0 0
Turkey
State/province [5] 0 0
Kayseri
Country [6] 0 0
United Kingdom
State/province [6] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Leiden University Medical Center
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
ZonMw: The Netherlands Organisation for Health Research and Development
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Horizon 2020 - European Commission
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is a prospective, non-randomized, open-label, two-centre phase I/II intervention study designed to treat children up to 24 months of age with RAG1-deficient SCID with an indication for allogeneic hematopoietic stem cell transplantation but lacking an HLA-matched donor. The study involves infusion of autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (hereafter called RAG1 LV CD34+ cells) in five patients with RAG1-deficient SCID.
Trial website
https://clinicaltrials.gov/study/NCT04797260
Trial related presentations / publications
Garcia-Perez L, van Eggermond M, van Roon L, Vloemans SA, Cordes M, Schambach A, Rothe M, Berghuis D, Lagresle-Peyrou C, Cavazzana M, Zhang F, Thrasher AJ, Salvatori D, Meij P, Villa A, Van Dongen JJM, Zwaginga JJ, van der Burg M, Gaspar HB, Lankester A, Staal FJT, Pike-Overzet K. Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID. Mol Ther Methods Clin Dev. 2020 Mar 31;17:666-682. doi: 10.1016/j.omtm.2020.03.016. eCollection 2020 Jun 12.
Public notes

Contacts
Principal investigator
Name 0 0
Arjan C Lankester, Prof.dr.
Address 0 0
Leiden University Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Arjan C Lankester, Prof. Dr.
Address 0 0
Country 0 0
Phone 0 0
0031715264871
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04797260