Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1)

X-linked Severe Combined Immunodeficiency Clinical Trial

Official title:

Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01175239
• Other study ID #: 06MI10
• Status: Active, not recruiting
• Phase: N/A
• First received: July 29, 2010
• Last updated: July 31, 2017
• Start date: April 2011
• Est. completion date: December 2018

Study information

• Verified date: October 2016
• Source: Great Ormond Street Hospital for Children NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

X-linked severe combined immunodeficiency (SCID-X1) is an inherited disorder that results in failure of development of the immune system in boys. This trial aims to treat SCID-X1 patients using gene therapy to replace the defective gene.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 16 Years

Eligibility

Inclusion Criteria:

1. No HLA identical (A,B,C,DR,DQ) family donor and no HLA identical unrelated donor available within 3 months of diagnosis or patients whose underlying clinical problems and prognosis would be significantly compromised by chemotherapy conditioning (including persisting pneumonitis, protracted diarrhoea requiring parental nutrition, ongoing visceral viral infection (herpes viruses, HSV,VZV,CMV, EBV or adenovirus), systemic BCG infection, virus-induced lymphoproliferation.

2. Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing

3. Parental/guardian voluntary consent

4. Boys between the ages of 0 and 16

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Severe Combined Immunodeficiency
• X-Linked Combined Immunodeficiency Diseases
• X-linked Severe Combined Immunodeficiency

Intervention

Genetic:
• Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre
Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Great Ormond Street Hospital for Children NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 2000 Apr 28;288(5466):669-72. — View Citation

Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S, Fischer A, Davies EG, Kuis W, Leiva L, Cavazzana-Calvo M. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med. 2002 Apr 18;346(16):1185-93. — View Citation

Thornhill SI, Schambach A, Howe SJ, Ulaganathan M, Grassman E, Williams D, Schiedlmeier B, Sebire NJ, Gaspar HB, Kinnon C, Baum C, Thrasher AJ. Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency. Mol Ther. 2008 Mar;16(3):590-8. doi: 10.1038/sj.mt.6300393. Epub 2008 Jan 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological reconstitution	Immunophenotyping: detection of naïve CD3+ T-cell numbers, CD4, CD8, TCRaß, TCR?d, CD16+CD56+ NK & gamma chain expression. TRECs may be enumerated as surrogate marker for new thymic emigrants post-gene therapy; Lymphocyte proliferation assays to test function of T cells; Representation of TCR families by flow cytometry (Vß phenotyping), & CDR3 PCR spectratyping (Vß spectratyping) to monitor physiological & potentially pathological clonal expansions; Restoration of antibody production (IgA, IgM, IgG) & serological responses to vaccinations & natural infections.	1-18 months post-infusion,then annually
Secondary	Incidence of adverse reactions	At each scheduled visit, adverse events that might have occurred since the previous visit or assessment will be elicited from the patient/parent/guardian.; The investigators will maintain a record of all adverse events/occurrences in patients participating in the clinical trial. This record will be noted in the patient's medical notes.; Adverse events that have a causal relationship to the IMP (ARs) and SAEs will be recorded on the AE reporting section of the CRF.	from consent until 5 years post-infusion of gene-modified cells
Secondary	Molecular characterisation of gene transfer	Quantification of transgene copy numbers is determined on sorted cell populations by real-time PCR methodology. Detailed integration analysis may be used to investigate specific clonal expansions.	until 5 years post-infusion of gene-modified cells
Secondary	Normalisation of nutritional status, growth, and development	Normalisation of nutritional status, growth, and development will be assessed at each follow-up visit by the investigator through clinical examinations.	until 5 years post-infusion of gene-modified cells