NCT01852071

Autologous CD34+ Hematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for the Human ADA Gene

Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA Complementary DNA (cDNA) by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 1 Month – 17 Years
• 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 the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA 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 cDNA will be used to transduce autologous CD34+ cells from the bone marrow of these subjects. The subjects will receive 4 mg/kg busulfan prior to re-infusion of their gene-modified cells. Safety 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 pegademase bovine (PEG-ADA) enzyme replacement therapy (ERT), which will be withheld at Day +30 following transplant. Efficacy studies to evaluate the level of immune reconstitution, will be performed in the first and second years of the study.

Conditions

• ADA-SCID

Interventions

Type	Name	Description
GENETIC	Infusion of autologous EFS-ADA LV CD34+ (OTL-101)	autologous EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously
DRUG	busulfan	Busulfan is used for non-myeloablative conditioning
DRUG	PEG-ADA ERT	PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment

Timeline

• Start date: 2013-08-02
• Primary completion: 2018-08-27
• Completion: 2018-08-27
• First posted: 2013-05-13
• Last updated: 2022-08-03
• Results posted: 2021-09-20

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study