Stem Cell Gene Therapy for Sickle Cell Disease

Phase 1

Active, not recruiting

• Conditions: Sickle Cell Disease
• Interventions: Biological: βAS3-FB vector transduced peripheral blood CD34+ cells

• Registration Number: NCT02247843
• Lead Sponsor: Donald B. Kohn, M.D.

Brief Summary

This Phase I clinical trial will assess the safety and initial evidence for efficacy of an autologous transplant of lentiviral vector modified peripheral blood for adults with severe sickle cell disease.

Detailed Description

Sickle cell disease (SCD) affects \~90,000 people in the U.S. who suffer significant neurological, lung, and kidney damage, as well as severe chronic pain episodes that adversely impact on quality of life. While current medical therapies for SCD can reduce short-term morbidity, the inevitable progressive deterioration in organ function results in a significant decrease in quality of health with early mortality. Allogeneic hematopoietic stem cell transplant (HSCT) can benefit patients with SCD, by providing a source for life-long production of normal red blood cells. However, allogeneic HSCT is limited by the availability of well-matched donors and immunological complications, especially for the more than 80% of patients who lack an HLA-identical sibling donor. Autologous HSCT using a patient's own peripheral blood stem cells that have been corrected by transfer of a modified human beta-globin gene that inhibits polymerization of the HbS (stem cell gene therapy) may provide a better therapeutic alternative, as it would avoid the immunologic complications and donor limitations of allogeneic HSCT.

Up to 6 subjects with SCD meeting eligibility criteria for disease severity and adequacy of organ function will be enrolled.

Following informed consent, enrolled subjects will be screened to confirm full eligibility for participation. A chronic red blood cell transfusions regimen will be given prior to stem cell collection and transplant. Subjects will undergo peripheral blood stem cell collection using plerixafor mobilization and apheresis. A portion of their stem cells will be cryopreserved as "back-up," with the remaining portion used to prepare the gene-modified Final Cellular Product: autologous peripheral blood CD34+ cells transduced ex vivo by the Lenti/G-βAS3-FB lentiviral vector to express an anti-sickling (βAS3) gene. The subject will receive marrow cytoreduction with busulfan prior to infusion of the gene-modified cells. The follow-up period will include an initial 2 years of active follow-up, where the subjects will be seen at intervals of no more than 3 months, followed by offer for enrollment into a long-term follow-up study during years 3-15.

The primary objectives of the Phase I study are to assess safety and feasibility, with secondary objectives to assess efficacy (engraftment, βAS3-globin gene expression, and effects on red blood cells function and clinical hematologic and disease parameters).

Study Timeline

• Study First Submitted: 2014-09-20
• Study First Submitted QC: 2014-09-23
• Study First Posted: 2014-09-25
• Study Start: 2014-12
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
βAS3-FB vector transduced peripheral blood CD34+ cells	βAS3-FB vector transduced peripheral blood CD34+ cells	This is a single arm study without randomization. All subjects will receive the intervention of BetaAS3 lentiviral vector-modified autologous peripheral blood stem cell transplant.

Primary Outcome Measures

Name	Time	Method
Evaluation of Safety	up to 24 months	1. Clinical toxicity: Absence of grade 3-4 SAEs; 2. Absence of replication-competent lentivirus (RCL): 3. Absence of monoclonal expansion or leukoproliferative disorder from vector insertional effects: To monitor for monoclonal expansion or leukoproliferative complications, LAM-PCR will be performed.; 4. Event-free survival. Event-free survival will be determined for each subject over the 24 months after gene therapy. An event is defined as death or performance of an allogeneic HSCT.; 5. Absence of humoral immune response to novel epitopes of βAS3-globin protein

Trial Locations

Locations (1)

University of California, Los Angeles (UCLA); 🇺🇸 Los Angeles, California, United States