Gene Therapy ADA Deficiency
Primary Purpose
Adenosine Deaminase Deficiency
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Intravenous infusion of transduced cells
Sponsored by
About this trial
This is an interventional treatment trial for Adenosine Deaminase Deficiency focused on measuring Adenosine deaminase deficiency, Gene therapy
Eligibility Criteria
Inclusion Criteria:
- Patients who lack a human leukocyte antigen (HLA)-genotypically identical bone marrow donor OR phenotypically matched family or unrelated donor AND who show incomplete immune reconstitution on Polyethylene glycol-modified adenosine deaminase (PEG-ADA) enzyme replacement therapy (defined by absolute CD4+ count <300 cell/mm3 and who remain on immunoglobulin replacement therapy)
- Diagnosis of ADA-SCID (Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA)confirmed by DNA sequencing OR by confirmed absence of <3% of ADA enzymatic activity in peripheral blood or (for neonates) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
- Parental/guardian/patient signed informed consent
Sites / Locations
- Great Ormond Street Hospital for Children NHS Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intravenous infusion of transduced cells
Arm Description
Intravenous infusion of transduced cells
Outcomes
Primary Outcome Measures
Immunological reconstitution
Measurement of Immunological reconstitution and Metabolic Correction. 5 year follow up of the last patient enrolled into study
Secondary Outcome Measures
Incidence of adverse reactions
Incidence of adverse reactions. 5 year follow up of the last patient enrolled into study
Molecular characterisation of gene transfer
Molecular characterisation of gene transfer. 5 year follow up of the last patient enrolled into study
Normalisation of nutritional status, growth, and development
Normalisation of nutritional status, growth, and development. 5 year follow up of the last patient enrolled into study
Full Information
NCT ID
NCT01279720
First Posted
January 18, 2011
Last Updated
September 11, 2015
Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT01279720
Brief Title
Gene Therapy ADA Deficiency
Official Title
Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
4. Oversight
5. Study Description
Brief Summary
Adenosine deaminase deficiency is an inherited disorder that results in severe abnormalities of the immune system and leaves children unable to fight infection. This trial aims to treat adenosine deaminase deficiency patients using gene therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenosine Deaminase Deficiency
Keywords
Adenosine deaminase deficiency, Gene therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous infusion of transduced cells
Arm Type
Experimental
Arm Description
Intravenous infusion of transduced cells
Intervention Type
Biological
Intervention Name(s)
Intravenous infusion of transduced cells
Intervention Description
Intravenous infusion of transduced cells
Primary Outcome Measure Information:
Title
Immunological reconstitution
Description
Measurement of Immunological reconstitution and Metabolic Correction. 5 year follow up of the last patient enrolled into study
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Incidence of adverse reactions
Description
Incidence of adverse reactions. 5 year follow up of the last patient enrolled into study
Time Frame
5 years
Title
Molecular characterisation of gene transfer
Description
Molecular characterisation of gene transfer. 5 year follow up of the last patient enrolled into study
Time Frame
5 years
Title
Normalisation of nutritional status, growth, and development
Description
Normalisation of nutritional status, growth, and development. 5 year follow up of the last patient enrolled into study
Time Frame
5 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who lack a human leukocyte antigen (HLA)-genotypically identical bone marrow donor OR phenotypically matched family or unrelated donor AND who show incomplete immune reconstitution on Polyethylene glycol-modified adenosine deaminase (PEG-ADA) enzyme replacement therapy (defined by absolute CD4+ count <300 cell/mm3 and who remain on immunoglobulin replacement therapy)
Diagnosis of ADA-SCID (Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA)confirmed by DNA sequencing OR by confirmed absence of <3% of ADA enzymatic activity in peripheral blood or (for neonates) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
Parental/guardian/patient signed informed consent
Facility Information:
Facility Name
Great Ormond Street Hospital for Children NHS Trust
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
12089448
Citation
Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A, Morecki S, Andolfi G, Tabucchi A, Carlucci F, Marinello E, Cattaneo F, Vai S, Servida P, Miniero R, Roncarolo MG, Bordignon C. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science. 2002 Jun 28;296(5577):2410-3. doi: 10.1126/science.1070104.
Results Reference
background
PubMed Identifier
8867866
Citation
Hoogerbrugge PM, van Beusechem VW, Fischer A, Debree M, le Deist F, Perignon JL, Morgan G, Gaspar B, Fairbanks LD, Skeoch CH, Moseley A, Harvey M, Levinsky RJ, Valerio D. Bone marrow gene transfer in three patients with adenosine deaminase deficiency. Gene Ther. 1996 Feb;3(2):179-83.
Results Reference
background
PubMed Identifier
7749407
Citation
Hershfield MS. PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency. Hum Mutat. 1995;5(2):107-12. doi: 10.1002/humu.1380050202.
Results Reference
background
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Gene Therapy ADA Deficiency
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