Gene Therapy for X-linked Severe Combined Immunodeficiency

NCT01410019 | Completed Phase 1 DMC

• 2 other identifiers: P0712042008-002380-14
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

X-linked Severe Combined Immunodeficiency

Keywords

X-linked Severe Combined Immunodeficiency (SCID-X1); severe infection; gene therapy; HLA identical family donor; without HLA identical unrelated donor

Outcome Measures

Primary Outcomes (1)

• Assessment of immunological reconstitution at short term

  T cells proliferation T cells and B cells repertory by immunofluorescence T, NK and B Lymphocytes phenotyping Immunoglobulins dosage IgG, A, M, E and antibody production

  month 4

Secondary Outcomes (2)

• Molecular characterization of gene transfer

  every 15 days during 3 months, once per month until 6 months, every 3 months until year 1, every year until year 10

• Analysis of activated proto-oncogene s expression

  every 4 months during 2 years and every 6 months indefinitely

Study Arms (1)

1

EXPERIMENTAL

Gene transfer

Other: Gene transfer

Interventions

Gene transfer OTHER

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

1

Eligibility Criteria

• Age: Up to 12 Months
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Boys diagnosed during the first year of life
• Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing
• No HLA identical family donor and no HLA identical unrelated donor (10/10 antigens) found in the 6 weeks following the beginning of the search. This period could be shortened if the probability to find a donor is low or if the clinical situation (gravity) required
• Presence of a severe infection: pneumonitis and / or chronic diarrhea, or infection with herpes viruses or parainfluenza type 3 or adenovirus, or disseminated BCG infection, or presence of severe diarrhea and a severe compromise of the general state with denutrition
• Or failure of a HLA HAPLO-identical bone marrow transplant within 10 years after transplantation
• In all cases:
• No family background of cancer in childhood.
• No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia of children
• Parental/guardian voluntary consent

You may not qualify if:

• Atypical health with autologous T\> 500/ml3
• Infection by HIV 1 or 2
• Allogeneic HSC completed (excluding situations of failure)
• Existence of an HLA identical family donor or HLA identical unrelated donor
• No severe infections in a child with a preserved general state
• Family background of cancer in childhood
• Detection of cytogenetic abnormality and / or rearrangement associated with acute leukemia of children
• No affiliation to a social security scheme (beneficiary or assignee)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Necker

Paris, 75015, France

Location

Related Publications (5)

• 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: 10784449 BACKGROUND

• 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: 11961146 BACKGROUND

• Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, Martinache C, Rieux-Laucat F, Latour S, Belohradsky BH, Leiva L, Sorensen R, Debre M, Casanova JL, Blanche S, Durandy A, Bushman FD, Fischer A, Cavazzana-Calvo M. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010 Jul 22;363(4):355-64. doi: 10.1056/NEJMoa1000164.

  PMID: 20660403 BACKGROUND

• 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: 25295500 RESULT

• 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: 30261899 DERIVED

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases; Infections

Interventions

Genetic Engineering

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques

Study Officials

• Alain Fischer, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: August 4, 2011
• Study Start: December 1, 2010
• Primary Completion: June 16, 2015
• Study Completion: June 16, 2015
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

FR (1)