NCT05432310

Gene Therapy for Adenosine Deaminase Severe Combined Immune Deficiency Using Peripheral Blood and EFS ADA Vector

Efficacy and Safety of Cryopreserved Autologous Mobilized Peripheral Blood CD34+ HSPCs Transduced Ex Vivo With the EFS-ADA Lentiviral Vector in Patients With Severe Combined Immune Deficiency Due To Adenosine Deaminase Deficiency

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 1 Month
• Healthy volunteers: Not accepted

Summary

The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from mobilized peripheral blood (mPB) of ADA-deficient SCID infants and children following human ADA gene transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.

Detailed description

The study is open to twenty (20) infants and children diagnosed with ADA-deficient SCID who did not have a medically eligible, human leukocyte antigen (HLA)-identical sibling donor for bone marrow transplantation. The EFS-ADA lentiviral vector with the human ADA complementary DNA (cDNA) will be used to transduce autologous CD34+ cells from Granulocyte Colony Stimulating Factor (G-CSF)/Plerixafor mobilized Peripheral Blood (mPB) of these subjects. The subjects will receive pharmacokinetically-adjusted busulfan reduced intensity conditioning prior to re-infusion of their gene-modified cells. Overall survival at two years is the primary endpoint. During the follow-up phase, the investigators aim to determine whether the cells could engraft and produce mature cells that contain and express the corrected ADA gene in the absence of pegylated adenosine deaminase (PEG-ADA) enzyme replacement therapy (ERT), which will be withheld starting on Day +30 following transplant. Efficacy studies to evaluate the level of immune reconstitution, will be performed in the two years of the study. Patients will be asked to enroll into a long-term follow-up study to reach a total of 15 years follow-up after gene therapy.

Conditions

• Adenosine Deaminase Severe Combined Immune Deficiency

Interventions

Type	Name	Description
COMBINATION_PRODUCT	A cryopreserved formulation of autologous mPB CD34+ hematopoietic stem and progenitor cells transduced ex vivo with the EFS-ADA lentiviral vector encoding the human ADA enzyme	Autologous transplantation of EFS-ADA lentiviral vector transduced, mPB CD34+ cells by central venous infusion, following reduced intensity conditioning with busulfan

Timeline

• Start date: 2023-01-04
• Primary completion: 2027-11-14
• Completion: 2027-12-31
• First posted: 2022-06-27
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study