Phase 2
N=19
A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants
β-thalassemia Major
Bottom Line
View on ClinicalTrials.gov: NCT01745120 ↗Enrolled (actual)
19
Serious AEs
52.6%
Results posted
May 2019
Primary outcome: Primary: Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24 — 90.0; 87.5; 88.9 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LentiGlobin BB305 Drug Product (Genetic)
- Age
- Pediatric, Adult · 12+ yrs
- Sex
- All
- Sponsor
- Genetix Biotherapeutics Inc.
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing βA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24 |
90.0; 87.5; 88.9 | — |
| PRIMARY Percentage of Participants Who Achieved Transfusion Independence (TI) |
80.0; 12.5; 50.0 | — |
| SECONDARY Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24 |
80.0; 12.5; 50.0; 80.0; 0; 44.4 | — |
| SECONDARY Duration of Transfusion Independence (TI) |
18.91; 16.13; 17.28 | — |
| SECONDARY Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI) |
2.00; 1.81; 1.81 | — |
| SECONDARY Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) |
17.12; 17.51; 17.51 | — |
| SECONDARY Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) |
10.44; 10.11; 10.41 | — |
| SECONDARY Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24 |
-100.00; -65.80; -90.74 | — |
| SECONDARY Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24 |
-100.00; -71.97; -92.38 | — |
| SECONDARY Weighted Average Nadir Hemoglobin (Hb) |
8.73; 9.38; 9.02; 9.97; 8.67; 9.39 | — |
| SECONDARY Number of Participants With Successful Neutrophil Engraftment |
10; 8; 18 | — |
| SECONDARY Time to Neutrophil Engraftment |
18.5; 19.5; 18.5 | — |
| SECONDARY Number of Participants With Successful Platelet Engraftment |
10; 8; 18 | — |
| SECONDARY Time to Platelet Engraftment |
50.5; 36.0; 39.5 | — |
| SECONDARY Transplant-related Mortality |
— | — |
| SECONDARY Overall Survival |
100 | — |
| SECONDARY Percentage of Participants Detected With Replication-competent Lentivirus (RCL) |
— | — |
| SECONDARY Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution |
0; 18 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
10; 8; 18; 6; 4; 10 | — |
Summary
This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in up to 18 participants (including at least 3 adolescents between 12 and 17 years of age, inclusive) with β-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene].
Eligibility Criteria
Inclusion criteria
- Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
- Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years.
- Eligible for allogeneic bone marrow transplant.
- Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Exclusion criteria
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
- A white blood cell (WBC) count 3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
- Kidney disease with a calculated creatinine clearance <30% normal value.
- Uncontrolled seizure disorder.
- Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin).
- A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
- Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
- Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
- Participation in another clinical study with an investigational drug within 30 days of Screening.
- Any prior or current malignancy or myeloproliferative disorder.
- Prior receipt of gene therapy.
Data sourced from ClinicalTrials.gov (NCT01745120). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.