LentiGlobin for Beta Thalassemia

No longer recruiting at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Genetix Biotherapeutics Inc.

Must not be taking: Investigational drugs

Disqualifiers: HIV, HBV, HCV, Malignancy, 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: 25

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of LentiGlobin BB305, a treatment for individuals with transfusion-dependent β-thalassemia (TDT). The focus is on those requiring regular blood transfusions due to specific genetic types of TDT. Participants must have received frequent blood transfusions for the past two years and be clinically stable enough for a type of stem cell transplant. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants an opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that LentiGlobin BB305 Drug Product is likely to be safe for humans?

Research has shown that the LentiGlobin BB305 Drug Product has promising safety results from earlier studies. In these studies, patients tolerated the gene therapy well, and no major safety issues emerged. The treatment uses the patient's own stem cells, modified with a special tool to deliver new genetic material into the cells.

Additionally, LentiGlobin BB305 has been compared to an older version, and evidence suggests it performs better. Importantly, the FDA has already approved this treatment under the name ZYNTEGLO for another condition, indicating a certain level of safety. Overall, existing research suggests that the treatment is safe for humans, with few reported side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for transfusion-dependent β-thalassemia, which primarily involve regular blood transfusions and iron chelation therapy to manage symptoms, LentiGlobin BB305 offers a groundbreaking approach by targeting the genetic root of the disease. This treatment involves using a lentiviral vector to insert a functional version of the β-globin gene into a patient's own stem cells, potentially allowing them to produce healthy red blood cells independently. Researchers are excited about LentiGlobin BB305 because it has the potential to significantly reduce or even eliminate the need for ongoing blood transfusions, offering a more sustainable and long-term solution for patients.

What evidence suggests that LentiGlobin BB305 Drug Product might be an effective treatment for transfusion-dependent β-thalassemia?

Research has shown that LentiGlobin BB305, the treatment under study in this trial, can help treat transfusion-dependent β-thalassemia (TDT). In earlier studies, patients who received LentiGlobin produced a special type of hemoglobin (HbA T87Q) in their red blood cells. This led to a reduced need for blood transfusions, with many patients requiring fewer or no regular transfusions. Another study found that the drug might improve blood health by reducing the breakdown of red blood cells. Overall, these findings suggest that LentiGlobin BB305 can help manage TDT by enhancing the body's ability to produce healthy red blood cells. ^{3 5 6 7 8}

Who Is on the Research Team?

Himal L Thakar, MD

Principal Investigator

Genetix Biotherapeutics Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

Clinically stable and eligible to undergo HSCT.

• Participants less than or equal to (<=) 50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Provided that the data monitoring committee (DMC) has approved enrolling participants younger than 5 years of age, participants younger than 5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.

Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year (mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be managed under standard thalassemia guidelines with >= 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants >=12 years).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of LentiGlobin BB305 Drug Product through autologous hematopoietic stem cell transplantation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of transfusion independence and quality of life

24 months

Regular visits (in-person and virtual) up to Month 24

Long-term Follow-up

Participants continue to be monitored for long-term safety and efficacy outcomes

Beyond 24 months

What Are the Treatments Tested in This Trial?

Interventions

• LentiGlobin BB305 Drug Product

How Is the Trial Designed?

Group I: LentiGlobin BB305 Drug Product Experimental Treatment 1 Intervention

LentiGlobin BB305 Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human βA-T87Q-globin)

Who Is Running the Clinical Trial?

Genetix Biotherapeutics Inc.

Lead Sponsor

bluebird bio

Lead Sponsor

Trials

21

Recruited

2,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02151526

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 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2117175

Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell ... One-time treatment with LentiGlobin resulted in sustained production of HbA T87Q in most red cells, leading to reduced hemolysis and complete resolution of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10849583/

LentiGlobin Administration to Sickle Cell Disease Patients A study evaluating the safety and efficacy of the lentiGlobin BB305 drug product in β-thalassemia major participants. [ Oct; 2023 ]. 2019 ...

4. investor.bluebirdbio.com investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-new-beta-thalassemia-major-and-severe-0

Press Release HGB-206 is an ongoing, open-label Phase 1 study designed to evaluate the safety and efficacy of LentiGlobin BB305 product candidate in the treatment of subjects ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4440358/

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 ...

6. fda.gov fda.gov/media/161472/download

ZYNTEGLO The ZYNTEGLO drug product consists of autologous CD34+ cells transduced with BB305 LVV, suspended in cryopreservation solution containing 5 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01745120

NCT01745120 | A Study Evaluating the Safety and Efficacy ... The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118502238

Initial Results from Study Hgb-206: A Phase 1 ... LentiGlobin BB305 gene therapy is a promising approach to decrease the HbS levels in patients with severe sickle cell disease.