Gene Therapy ADA Deficiency

Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency

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.

Study Overview

• Status: Completed
• Conditions: Adenosine Deaminase Deficiency
• Intervention / Treatment: Biological: Intravenous infusion of transduced cells

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • Great Ormond Street Hospital for Children NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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)
2. 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
3. Parental/guardian/patient signed informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous infusion of transduced cells	Biological: Intravenous infusion of transduced cells; Intravenous infusion of transduced cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological reconstitution	Measurement of Immunological reconstitution and Metabolic Correction. 5 year follow up of the last patient enrolled into study	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse reactions	Incidence of adverse reactions. 5 year follow up of the last patient enrolled into study	5 years
Molecular characterisation of gene transfer	Molecular characterisation of gene transfer. 5 year follow up of the last patient enrolled into study	5 years
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	5 years

Collaborators and Investigators

• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Estimate): September 14, 2015
• Last Update Submitted That Met QC Criteria: September 11, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Gene therapy; Adenosine deaminase deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Severe Combined Immunodeficiency
• Other Study ID Numbers: 03MI14