NCT01175239

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2011

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 29, 2010

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 4, 2010

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
7.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

August 1, 2017

Status Verified

October 1, 2016

Enrollment Period

7.7 years

First QC Date

July 29, 2010

Last Update Submit

July 31, 2017

Conditions

X-linked Severe Combined Immunodeficiency

Keywords

X-linked severe combined immunodeficiency, gene therapyPatients will be enrolled following diagnosis and referral to Great Ormond Street Immunology Service.

Outcome Measures

Primary Outcomes (1)

  • Immunological reconstitution

    * Immunophenotyping: detection of naïve CD3+ T-cell numbers, CD4, CD8, TCRαβ, TCRγδ, 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 (Vβ phenotyping), \& CDR3 PCR spectratyping (Vβ 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 Outcomes (3)

  • Incidence of adverse reactions

    from consent until 5 years post-infusion of gene-modified cells

  • Molecular characterisation of gene transfer

    until 5 years post-infusion of gene-modified cells

  • Normalisation of nutritional status, growth, and development

    until 5 years post-infusion of gene-modified cells

Study Arms (1)

Single infusion of autologous CD34+ cells

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

Interventions

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

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

Single infusion of autologous CD34+ cells

Eligibility Criteria

AgeUp to 16 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.
  • Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing
  • Parental/guardian voluntary consent
  • Boys between the ages of 0 and 16

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Great Ormond Street Hospital for Children NHS Trust

London, WC1N 3JH, United Kingdom

Location

Related Publications (5)

  • 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.

    PMID: 18180772BACKGROUND

  • 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. doi: 10.1126/science.288.5466.669.

    PMID: 10784449BACKGROUND

  • 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. doi: 10.1056/NEJMoa012616.

    PMID: 11961146BACKGROUND

  • Clarke EL, Connell AJ, Six E, Kadry NA, Abbas AA, Hwang Y, Everett JK, Hofstaedter CE, Marsh R, Armant M, Kelsen J, Notarangelo LD, Collman RG, Hacein-Bey-Abina S, Kohn DB, Cavazzana M, Fischer A, Williams DA, Pai SY, Bushman FD. T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency. Genome Med. 2018 Sep 28;10(1):70. doi: 10.1186/s13073-018-0580-z.

    PMID: 30261899DERIVED

  • Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S, Bleesing J, Blondeau J, de Boer H, Buckland KF, Caccavelli L, Cros G, De Oliveira S, Fernandez KS, Guo D, Harris CE, Hopkins G, Lehmann LE, Lim A, London WB, van der Loo JC, Malani N, Male F, Malik P, Marinovic MA, McNicol AM, Moshous D, Neven B, Oleastro M, Picard C, Ritz J, Rivat C, Schambach A, Shaw KL, Sherman EA, Silberstein LE, Six E, Touzot F, Tsytsykova A, Xu-Bayford J, Baum C, Bushman FD, Fischer A, Kohn DB, Filipovich AH, Notarangelo LD, Cavazzana M, Williams DA, Thrasher AJ. A modified gamma-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med. 2014 Oct 9;371(15):1407-17. doi: 10.1056/NEJMoa1404588.

    PMID: 25295500DERIVED

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases

Interventions

propeptide convertase 5, rat

Condition Hierarchy (Ancestors)

Genetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSevere Combined ImmunodeficiencyPrimary Immunodeficiency DiseasesInfant, Newborn, DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 29, 2010

First Posted

August 4, 2010

Study Start

April 1, 2011

Primary Completion

December 1, 2018

Study Completion

December 1, 2018

Last Updated

August 1, 2017

Record last verified: 2016-10

Locations

GB(1)