Gene Transfer for Sickle Cell Disease

Not currently recruiting at 1 trial location
AF
CD
Overseen ByColleen Dansereau, RN
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: David Williams
Must be taking: Hydroxyurea
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for people with sickle cell disease, a condition causing painful episodes and other serious complications. The treatment uses a special virus to introduce new genetic material into a person's own blood stem cells to increase fetal hemoglobin, potentially alleviating symptoms. This approach resembles a bone marrow transplant but uses the patient's own cells, reducing risks associated with donor cells. Individuals with severe sickle cell disease, who have experienced frequent pain crises or other complications and have not improved with standard treatments like hydroxyurea, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients who have not improved with hydroxyurea or cannot tolerate it are eligible, suggesting that continuing hydroxyurea might be allowed. It's best to discuss your specific medications with the trial team.

What prior data suggests that this gene therapy method is safe for treating sickle cell disease?

Research shows that gene therapy for sickle cell disease holds great promise. Studies have found that patients receiving this treatment experienced a significant drop in sickle cell episodes—by over 90% in some cases. This indicates the therapy is not only effective but also generally well-tolerated.

Although the treatment remains in early testing stages, it is important to note that the FDA has approved similar gene therapies for sickle cell disease, indicating confidence in their safety. These therapies use a modified virus to make the necessary gene changes in a patient’s own cells, reducing the risk of complications often seen with donor stem cells, such as graft-versus-host disease, where the donor's cells attack the patient's body.

As with any new treatment, monitoring for side effects is crucial. However, this approach appears to be a safe and exciting option for people with sickle cell disease.1234

Why do researchers think this study treatment might be promising?

Most treatments for sickle cell disease focus on managing symptoms or preventing complications, often using medications like hydroxyurea or regular blood transfusions. But this new gene transfer therapy works differently, targeting the root cause of the disease. It involves infusing a patient's own bone marrow cells that have been genetically modified to produce short-hairpin RNA targeting BC11A, a gene that plays a role in sickle cell formation. This approach could potentially offer a one-time, long-term solution rather than ongoing treatment, which is why researchers are particularly excited about its potential.

What evidence suggests that this gene therapy could be an effective treatment for sickle cell disease?

Research shows that gene therapy for sickle cell disease holds promise. In this trial, participants will receive a single infusion of autologous bone marrow-derived CD34+ HSC cells transduced with a lentiviral vector containing a short-hairpin RNA targeting BC11A. Studies using similar gene delivery tools have shown they can increase fetal hemoglobin, which helps reduce the effects of sickle hemoglobin. Specifically, one study found that patients who received gene-modified stem cells experienced less sickling of their blood cells. Another study demonstrated that these tools could effectively correct sickle cell disease by adding genes that prevent sickling. While it might not completely stop all sickling, this method has shown significant improvement in tests. Overall, early evidence suggests that gene therapy could be an effective treatment for sickle cell disease.14567

Who Is on the Research Team?

EE

Erica Esrick, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for people aged 3-40 with severe Sickle Cell Disease (SCD) who've had multiple pain events, acute chest syndrome, or need chronic transfusions. They must have tried hydroxyurea without success and can't have a matching bone marrow donor. Participants should be in stable health otherwise and willing to follow up for 15 years.

Inclusion Criteria

I am between 3 and 40 years old.
Parental/guardian/patient signed informed consent
Willingness to return for follow-up for 15 years
See 9 more

Exclusion Criteria

I cannot undergo bone marrow harvest or take certain medications due to health reasons.
Positive HIV serology or HIV nucleic acid testing, or positive serology for HCV, HBV, or HTLV
Non-compliance with study procedures
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients receive blood transfusions for 3 months prior to the planned date of product infusion to achieve a HbS level ≤ 30%

12 weeks

Treatment

Infusion of autologous bone marrow derived CD34+ HSC cells transduced with lentiviral vector

1 week
Inpatient stay for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including rescue of hematopoiesis and expression of transgene

2 years
Regular visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

  • Gene Transfer for Sickle Cell Disease

Trial Overview

The trial tests gene therapy using the patient's own modified blood stem cells to treat SCD. It involves a single infusion of these engineered cells aiming to increase fetal hemoglobin production which could potentially cure SCD.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Treatment armExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

David Williams

Lead Sponsor

Trials
5
Recruited
60+

Citations

Clinical Outcomes of Lenti/G-βAS3-FB Lentiviral Vector ...

Here, we report the clinical outcomes of four patients who underwent gene-modified autologous stem cell transplantation using the Lenti/G-βAS3-FB vector. Five ...

Gene therapies for sickle cell disease: Effectiveness and ...

This report presents the summary of our systematic literature review and cost-effectiveness analysis and highlights the key policy recommendations.

Novel lentiviral vectors for gene therapy of sickle ...

However, despite the good gene transfer efficiency in SCD HSPCs, RBC sickling was only partially corrected, even at a high vector copy number ...

An Optimized Lentiviral Vector Efficiently Corrects the ...

Together, these results demonstrate the ability of a high-titer LV to express elevated levels of a potent anti-sickling HBB transgene ameliorating the SCD cell ...

FDA Approves First Gene Therapies to Treat Patients with ...

The FDA approved the first cell-based gene therapies, Casgevy and Lyfgenia, for the treatment of sickle cell disease in patients 12 years ...

Gene therapy for sickle cell disease: moving from the bench to ...

Both patients had a >90% reduction in acute sickling episodes after treatment. Outcome data on an additional 2 patients are pending. Although the increase in ...

The future of sickle cell disease treatment through gene therapy

Gene therapy offers a potential cure for SCD, reducing the need for ongoing treatments and significantly improving quality of life. It can lower ...