Gene Therapy ADA Deficiency

Adenosine Deaminase Deficiency Clinical Trial

Official title:

Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01279720
• Other study ID #: 03MI14
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 18, 2011
• Last updated: September 11, 2015
• Start date: October 2003
• Est. completion date: November 2013

Study information

• Verified date: September 2015
• Source: Great Ormond Street Hospital for Children NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenosine Deaminase Deficiency
• Agammaglobulinemia
• Severe Combined Immunodeficiency

Intervention

Biological:
• Intravenous infusion of transduced cells
Intravenous infusion of transduced cells

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Great Ormond Street Hospital for Children NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological reconstitution	Measurement of Immunological reconstitution and Metabolic Correction. 5 year follow up of the last patient enrolled into study	5 years	No
Secondary	Incidence of adverse reactions	Incidence of adverse reactions. 5 year follow up of the last patient enrolled into study	5 years	Yes
Secondary	Molecular characterisation of gene transfer	Molecular characterisation of gene transfer. 5 year follow up of the last patient enrolled into study	5 years	No
Secondary	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	No