35 Participants Needed

Gene Therapy for Sickle Cell Disease

Recruiting at 11 trial locations
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Overseen Bybluebird bio
Age: < 65
Sex: Any
Trial Phase: Phase 3
Sponsor: bluebird bio
Must be taking: Hydroxyurea
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy treatment, called bb1111, for sickle cell disease. The goal is to determine if a one-time stem cell transplant can help individuals with sickle cell disease by modifying their genes to produce healthier blood cells. It targets those who have experienced at least four painful episodes in the past two years, despite receiving care. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on hydroxyurea, your neutrophil count requirements are different, which might imply some consideration for this medication.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the gene therapy bb1111, also known as LentiGlobin BB305, has been studied for its safety and effectiveness in treating sickle cell disease (SCD). The treatment helps produce a stable form of hemoglobin, called HbA T87Q, which reduces the breakdown of red blood cells—a common issue for people with SCD.

In earlier studies, participants generally tolerated the treatment well. Although all treatments can have side effects, these studies reported no major safety concerns. This suggests the treatment is likely safe, but discussing any potential risks with the research team before joining a trial is important.12345

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike the standard treatments for sickle cell disease, which often involve regular blood transfusions and pain management medications, bb1111 is a gene therapy that targets the root cause of the condition. This treatment is unique because it uses a lentiviral vector to introduce a modified beta-globin gene into the patient's own stem cells. By doing so, bb1111 has the potential to produce normal hemoglobin and significantly reduce the symptoms of sickle cell disease. Researchers are excited about bb1111 because it offers a one-time treatment that could provide a long-term solution, moving beyond managing symptoms to potentially curing the disease.

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

Research shows that the gene therapy bb1111, also known as LentiGlobin, may help treat sickle cell disease (SCD). In this trial, participants will receive a single dose of bb1111, which uses a special tool to add a modified gene into the patient's stem cells. This new gene helps produce healthier red blood cells, reducing the symptoms of sickle cell disease. In earlier studies, patients who received this treatment experienced fewer painful sickle cell crises. Early results indicate that many patients continue to have better blood counts and fewer symptoms over time. Overall, these findings suggest that bb1111 could be a promising option for people with SCD.12467

Who Is on the Research Team?

AC

Anjulika Chawla, MD, FAAP

Principal Investigator

bluebird bio, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals aged 2 to 50 with sickle cell disease (SCD), who have had at least four pain episodes in the last two years and either failed hydroxyurea treatment or can't tolerate it. Participants must weigh over 6 kg, have a certain level of physical ability, and agree to use contraception if applicable. Those with inadequate bone marrow function, prior malignancies, genetic risks for other blood disorders, or severe cerebral vasculopathy cannot join.

Inclusion Criteria

I am mostly able to care for myself and carry out daily activities.
Experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent
I have been treated for sickle cell disease and followed at a medical center with detailed records for the past 2 years.
See 6 more

Exclusion Criteria

I am currently pregnant, breastfeeding, or planning to become pregnant.
I cannot receive red blood cell transfusions.
My bone marrow is not working properly.
See 14 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Apheresis

Plerixafor mobilization and apheresis are used for collection of autologous CD34+ hematopoietic stem cells

1-2 weeks

Transplantation

Subjects receive a single dose of Drug Product manufactured with autologous CD34+ hematopoietic stem cells transduced with BB305 lentiviral vector

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including resolution of VOEs and globin response

24 months

What Are the Treatments Tested in This Trial?

Interventions

  • bb1111
Trial Overview The study tests a gene therapy called bb1111 in about 35 people with SCD. It's an open-label Phase 3 trial where participants receive one dose of the therapy through hematopoietic stem cell transplantation (HSCT). The goal is to see how well this new treatment works compared to traditional treatments.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: bb1111Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

bluebird bio

Lead Sponsor

Trials
21
Recruited
2,000+

Genetix Biotherapeutics Inc.

Lead Sponsor

Published Research Related to This Trial

A new therapeutic approach combining lentiviral gene addition and CRISPR-Cas9 strategies shows promise for treating sickle cell disease (SCD) by allowing for effective gene editing and expression of anti-sickling hemoglobins with lower vector copy numbers.
This method not only enhances the levels of beneficial hemoglobins but also reduces the risk of genotoxicity associated with high vector amounts, making it a safer option for patients with SCD.
Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease.Ramadier, S., Chalumeau, A., Felix, T., et al.[2023]
A CRISPR-Cas9 gene correction strategy demonstrated up to 60% correction of the sickle cell disease-causing mutation in patient-derived hematopoietic stem cells, showing promising efficacy for potential treatment.
Preclinical studies in mice showed that the corrected cells engrafted successfully without signs of abnormal blood cell formation or tumor development, indicating a favorable safety profile for this gene therapy approach.
Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease.Lattanzi, A., Camarena, J., Lahiri, P., et al.[2022]
The BCH-BB694 lentiviral vector effectively reactivates fetal hemoglobin production while reducing harmful adult sickle hemoglobin in sickle cell disease, showing a 3- to 5-fold increase in fetal hemoglobin levels in transduced cells.
Preclinical studies indicate that BCH-BB694 is non-toxic and can be produced at a clinically relevant scale, supporting its potential for safe and effective use in human trials for treating sickle cell disease.
Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.Brendel, C., Negre, O., Rothe, M., et al.[2020]

Citations

Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell ...Gene therapy with LentiGlobin for sickle cell disease (bb1111 ... lentiviral transfer of the β(A(T87Q))-globin gene. Hum Gene Ther 2016;27 ...
Gene Therapy of the β-Hemoglobinopathies by Lentiviral ...... LentiGlobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease ... Lentiviral Vector Encoding the Normal Human β-Globin Gene, July 2012 ...
NCT04293185 | A Study Evaluating Gene Therapy With ...A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease ... BB305 LVV encoding the βA-T87Q-globin gene, suspended in cryopreservation ...
A Study Evaluating the Safety and Efficacy of Lovo-cel in ...... BB305 lentiviral vector encoding the human beta-A-T87Q globin gene. This participant's drug product was produced in 2 lots each using two different ...
5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/36161320/
Lovo-cel gene therapy for sickle cell disease... lentiviral vector encoding a modified β-globin gene (β A-T87Q ) to ... lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy ...
Preclinical Evaluation of Efficacy and Safety of an Improved ...Overall, the data from the in vitro and in vivo nonclinical studies indicate a better efficacy of the LentiGlobin BB305 compared to the LentiGlobin HPV569 ...
NCT02151526 | A Study Evaluating the Safety and Efficacy ...This is a Phase 1/2, open label, safety, and efficacy study of the administration of LentiGlobin BB305 Drug Product to participants with either transfusion ...
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