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Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01410019
Recruitment Status : Completed
First Posted : August 4, 2011
Last Update Posted : September 28, 2021
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
X-linked Severe Combined Immunodeficiency Other: Gene transfer Phase 1 Phase 2

Detailed Description:

The objective of this protocol is to reinitiate an ex vivo gene therapy clinical protocol to treat patients with SCID-X1 without HLA identical family donor nor HLA identical unrelated donor (bone marrow and cord blood) available in an adequate time with the clinical conditions of the patient at diagnosis (approximately 6 weeks). This clinical protocol No. 2 of SCID-X1 must be as efficient than the previous one but must involve a risk of insertional mutagenesis significantly reduced as compared to the first protocol.

The main purpose of the study is the study of toxicity: tolerance and incidence of serious adverse effects.

Secondary goals are the evaluation of immune reconstitution allowing the cure of infections present at the time of gene therapy, assessment of integration sites, and finally the long-term correction of immunosuppression.

  1. safety assessment : clinical effects, possible emergence of clonal lymphocyte proliferation, potential activation of proto-oncogene;
  2. efficacy assessment of ex vivo transduction of CD34 + hematopoietic stem cells of the patient through the use of retroviral vector pSRS11.EFS.IL2RG.pre;
  3. assessment of immune reconstitution : phenotype, number and function of different T, NK and B cells subpopulations;
  4. longitudinal evaluation of clinical effects in terms of improvement or complete restoration of immunity;
  5. biological efficacy assessment of this new vector SIN, assessment of molecular characteristics of retroviral integration.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2
Study Start Date : December 2010
Actual Primary Completion Date : June 16, 2015
Actual Study Completion Date : June 16, 2015

Arm Intervention/treatment
Experimental: 1
Gene transfer
Other: Gene transfer
Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) GAMMARETROVIRAL vector pSRS11.EFS.IL2RG.pre

Primary Outcome Measures :
  1. Assessment of immunological reconstitution at short term [ Time Frame: month 4 ]
    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

Secondary Outcome Measures :
  1. Molecular characterization of gene transfer [ Time Frame: every 15 days during 3 months, once per month until 6 months, every 3 months until year 1, every year until year 10 ]
    PCR of vector

  2. Analysis of activated proto-oncogene s expression [ Time Frame: every 4 months during 2 years and every 6 months indefinitely ]
    Immunofluorescence analysis of the relative expression of different families of TCR alpha beta et gamma delta LAM PCR analysis and sequencing of integration sites

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion criteria :

  • 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

Exclusion criteria :

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01410019

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Hopital Necker
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Study Director: Alain Fischer, MD, PhD Assistance Publique - Hôpitaux de Paris
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01410019    
Other Study ID Numbers: P071204
2008-002380-14 ( EudraCT Number )
First Posted: August 4, 2011    Key Record Dates
Last Update Posted: September 28, 2021
Last Verified: September 2021
Keywords provided by Assistance Publique - Hôpitaux de Paris:
X-linked Severe Combined Immunodeficiency (SCID-X1)
severe infection
gene therapy
HLA identical family donor
without HLA identical unrelated donor
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
X-Linked Combined Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Genetic Diseases, X-Linked