NCT03282656

Gene Transfer for Sickle Cell Disease

Active, enrolled Phase 1 Last updated 9 January 2026

What this trial tests

Phase 1 trial testing single infusion of autologous bone marrow derived CD34+ HSC cells transduced with the lentiviral vector containing a short-hairpin RNA targeting BCL11a in Sickle Cell Disease in 10 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

13 February 2018

Primary endpoint
13 May 2026

13 November 2026

Quick facts

Lead sponsor	David Williams
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	13 February 2018
Primary completion	13 May 2026
Estimated completion	13 November 2026
Sites	2 locations across United States

Drugs / interventions tested

• single infusion of autologous bone marrow derived CD34+ HSC cells transduced with the lentiviral vector containing a short-hairpin RNA targeting BCL11a

Conditions studied

• Sickle Cell Disease — all drugs for Sickle Cell Disease →

Sponsor

David Williams — full company profile →

Who can join

Adults 3 to 40, any sex, with Sickle Cell Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

A promising approach for the treatment of genetic diseases is called gene therapy. Gene therapy is a relatively new field of medicine that uses genetic material (mostly DNA) from the patient to treat his or her own disease. In gene therapy, the investigators introduce new genetic material in order to fix or replace the patient's disease gene, with the goal of curing the disease. The procedure is similar to a bone marrow transplant, in that the patient's malfunctioning blood stem cells are reduced or eliminated using chemotherapy, but it is different because instead of using a different person's (donor) blood stem cells for the transplant, the patient's own blood stem cells are given back after the new genetic material has been introduced into those cells. This approach has the advantage of eliminating any risk of GVHD, reducing the risk of graft rejection, and may also allow less chemotherapy to be utilized for the conditioning portion of the transplant procedure. The method used to introduce the gene into the patient's own blood stem cells is to engineer and use a modified version of a virus (called a 'vector') that efficiently inserts the "correcting" genetic material into the cells. The vector is a specialized biological medicine that has been formulated for use in human beings.

The investigators have recently discovered a gene that is very important in the control of fetal hemoglobin expression. Increasing the expression of this gene in sickle cell patients could increase the amount of fetal hemoglobin while simultaneously reducing the amount of sickle hemoglobin in their blood, and therefore potentially cure the condition. In summary, the advantages of a gene therapy approach include: 1) it can be used even if the patient does not have a matched donor available; 2) it may allow a reduction in the amount of chemotherapy required to prepare the patient for the transplant; and 3) it will avoid the strong medicines often required to prevent and treat GVHD and rejection. The goal is to test whether this approach is safe, and whether using gene therapy to change the expression of this particular gene will lead to increased fetal hemoglobin production in people with sickle cell disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Post-Transcriptional Genetic Silencing of <i>BCL11A</i> to Treat Sickle Cell Disease.
   Esrick EB, Lehmann LE, Biffi A, Achebe M, et al · · 2021 · cited 310× · PMID 33283990 · DOI 10.1056/nejmoa2029392
2. RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.
   Yu AM, Choi YH, Tu MJ. · · 2020 · cited 271× · PMID 32929000 · DOI 10.1124/pr.120.019554
3. Recent Advances in the Treatment of Sickle Cell Disease.
   Salinas Cisneros G, Thein SL. · · 2020 · cited 110× · PMID 32508672 · DOI 10.3389/fphys.2020.00435
4. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.
   Tucci F, Galimberti S, Naldini L, Valsecchi MG, et al · · 2022 · cited 109× · PMID 35288539 · DOI 10.1038/s41467-022-28762-2
5. Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission.
   Piel FB, Rees DC, DeBaun MR, Nnodu O, et al · · 2023 · cited 100× · PMID 37451304 · DOI 10.1016/s2352-3026(23)00096-0
6. Fetal hemoglobin in sickle cell anemia.
   Steinberg MH. · · 2020 · cited 77× · PMID 32808012 · DOI 10.1182/blood.2020007645
7. Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients.
   Esrick EB, Manis JP, Daley H, Baricordi C, et al · · 2018 · cited 69× · PMID 30282642 · DOI 10.1182/bloodadvances.2018016725
8. Gene therapy for sickle cell disease: moving from the bench to the bedside.
   Abraham AA, Tisdale JF. · · 2021 · cited 66× · PMID 34232993 · DOI 10.1182/blood.2019003776