Gene Therapy for Sickle Cell Disease

Recruiting at 9 trial locations

Overseen By bluebird bio

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: bluebird bio

Must be taking: Hydroxyurea

Must not be taking: Anticoagulants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using bb1111 (also known as LentiGlobin BB305 Drug Product for SCD).

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.

What data supports the effectiveness of the treatment bb1111 for sickle cell disease?

The treatment bb1111, also known as LentiGlobin, involves gene therapy that uses a modified gene to produce a type of hemoglobin that doesn't sickle. Preclinical studies show that this approach can effectively increase the production of healthy hemoglobin, which helps prevent the sickling of red blood cells, a key problem in sickle cell disease. ^{1 2 3 4 5}

Is gene therapy for sickle cell disease generally safe in humans?

Preclinical studies show that the gene therapy using lentiviral vectors for sickle cell disease is non-toxic and safe, with no increased risk of cancer in lab tests. However, there have been concerns about leukemia in some patients, possibly linked to the therapy, but these cases are still being studied to understand the exact cause. ^{1 4 6 7 8}

How is the gene therapy treatment bb1111 for sickle cell disease different from other treatments?

The gene therapy treatment bb1111 (lovotibeglogene autotemcel) is unique because it involves modifying a patient's own stem cells to produce a special type of hemoglobin that prevents sickling of red blood cells, offering a potential one-time, lifelong cure without the need for a matched donor, unlike traditional treatments that often require ongoing management or donor matches. ^{1 2 4 5 9}

Research Team

Anjulika Chawla, MD, FAAP

Principal Investigator

bluebird bio, Inc.

Eligibility Criteria

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.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: bb1111 Experimental Treatment 1 Intervention

Subjects will receive treatment with a single dose of Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. Plerixafor mobilization and apheresis will also be used for collection of rescue cells.

Who Is Running the Clinical Trial?

bluebird bio

Lead Sponsor

Trials

21

Recruited

2,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

A Phase I study involving 28 patients with sickle cell disease found that ICA-17043 was well tolerated with no dose-limiting adverse events, indicating a good safety profile for this medication.

The pharmacokinetics showed that the total systemic exposure to ICA-17043 increased with higher doses, and the drug has a long half-life of 12.8 days, suggesting that once-daily dosing could effectively maintain therapeutic levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation study of ICA-17043 in patients with sickle cell disease. Ataga, KI., Orringer, EP., Styles, L., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease. Ramadier, S., Chalumeau, A., Felix, T., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Genetic Therapies for Sickle Cell Disease. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Dose-escalation study of ICA-17043 in patients with sickle cell disease. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling βAS3 Globin for Gene Therapy for Sickle Cell Disease. [2020]