Gene Therapy for X-linked Severe Combined Immunodeficiency

Phase 1

Completed

• Conditions: X-linked Severe Combined Immunodeficiency
• Interventions: Other: Gene transfer

• Registration Number: NCT01410019
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2011-06-21
• Study First Submitted QC: 2011-08-03
• Study First Posted: 2011-08-04
• Primary Completion: 2015-06-16
• Study Completion: 2015-06-16
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-22
• Last Update Posted: 2021-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Gene transfer	Gene transfer

Primary Outcome Measures

Name	Time	Method
Assessment of immunological reconstitution at short term	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

Name	Time	Method
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	PCR of vector
Analysis of activated proto-oncogene s expression	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

Trial Locations

Locations (1)

Hopital Necker; 🇫🇷 Paris, France