NCT03825783

A Gene Therapy Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I

Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector Encoding the ITGB2 Gene.

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Rocket Pharmaceuticals Inc. · Industry
• Sex: All
• Age: 3 Months
• Healthy volunteers: Not accepted

Summary

The primary purpose of the Phase I portion of the study is to determine the safety profile and preliminary evidence of efficacy associated with infusion of autologous gene-corrected hematopoietic stem cells.

Detailed description

The study is a pediatric non-randomized open-label Phase I clinical trial. This will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the ITGB2 gene in subjects with severe Leukocyte Adhesion Deficiency-I (LAD-I). Subjects will undergo mobilization and collection of peripheral blood hematopoietic stem cells (HSCs) with granulocyte-colony stimulating factor (G-CSF) and plerixafor or bone marrow harvest in select circumstances. HSCs will then be transduced with the therapeutic vector (Chim.hCD18-LV), with the intent of enabling stable integration of the provirus in the genome of stem and progenitor cells. If the number of CD34+ cells that are cryopreserved is at least 4×10E6 total CD34+ cells/kg, subjects will receive myeloablative conditioning with intravenous busulfan. The gene-modified CD34+ cells will be then transplanted back into the subject. Once engrafted, it is anticipated that the gene-modified stem and progenitor cells will enable hematopoiesis, generating blood cells in which the integrated therapeutic gene (ITGB2) will be transcribed and translated to produce the therapeutic CD18 protein with a preferential high expression in mature myeloid cells. Leukocytes expressing a functional CD18 will have the capability to arrest on endothelial surfaces and extravasate to infectious sites, enabling a competent antimicrobial response and reversing the clinical disorder.

Conditions

• Leukocyte Adhesion Defect - Type I

Interventions

Type	Name	Description
BIOLOGICAL	RP-L201	CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE.

Timeline

• Start date: 2019-04-15
• Primary completion: 2021-10-01
• Completion: 2021-10-01
• First posted: 2019-01-31
• Last updated: 2021-12-07

Locations

1 site across 1 country: Spain