Phase 3
N=19
A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia
Beta-Thalassemia
Bottom Line
View on ClinicalTrials.gov: NCT03207009 ↗Enrolled (actual)
19
Serious AEs
31.6%
Results posted
Dec 2023
Primary outcome: Primary: Percentage of Participants Who Have Achieved Transfusion Independence (TI) — 88.9 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- LentiGlobin BB305 Drug Product (Genetic)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Genetix Biotherapeutics Inc.
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Have Achieved Transfusion Independence (TI) |
88.9 | — |
| SECONDARY Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24 |
88.9 | — |
| SECONDARY Duration of Transfusion Independence (TI) |
20.86 | — |
| SECONDARY Time From Drug Product Infusion to Achievement of Transfusion Independence (TI) |
15.67 | — |
| SECONDARY Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI) |
10.817 | — |
| SECONDARY Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR) |
94.4 | — |
| SECONDARY Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume |
94.4; 94.4; 94.4; 94.4; 88.9 | — |
| SECONDARY Annualized Number of pRBC Transfusions |
0.68 | — |
| SECONDARY Annualized Volume of pRBC Transfusions |
11.589 | — |
| SECONDARY Time From Drug Product Infusion to Last pRBC Transfusion |
0.986 | — |
| SECONDARY Time From Last pRBC Transfusion to 24 Months |
23.211 | — |
| SECONDARY Weighted Average Nadir Hemoglobin (Hb) |
10.653 | — |
| SECONDARY Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24 |
10.41; 10.61; 10.65; 11.00; 10.82 | — |
| SECONDARY Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24 |
11; 4; 3; 1; 0; 13 | — |
| SECONDARY Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion |
61.1 | — |
| SECONDARY Time From Last Iron Chelation Use to Last Follow-up |
17.81 | — |
| SECONDARY Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion |
2 | — |
| SECONDARY Annualized Phlebotomy Therapy Usage Following Drug Product Infusion |
4.22 | — |
| SECONDARY Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI) |
3.171; 1.033 | — |
| SECONDARY Change From Baseline in Cardiac T2* on MRI |
-0.2; 0.2 | — |
| SECONDARY Change From Baseline in Serum Ferritin |
87.3; -605.2 | — |
| SECONDARY Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24 |
-6.20; -3.49; 2.96; 4.84 | — |
| SECONDARY Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24 |
0.3; 2.0 | — |
| SECONDARY Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24 |
-3.6; -2.4 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score |
0.33; 2.58 | — |
| SECONDARY Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24 |
-0.89; 1.09; 2.42; 2.08 | — |
Summary
This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
Eligibility Criteria
Inclusion Criteria
- Participants less than or equal to ( = 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants >=12 years).
- Clinically stable and eligible to undergo HSCT.
- Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Exclusion Criteria
- Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least one β-globin gene (HBB) allele.
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
- A white blood cell (WBC) count less than (<) 3×10^9/liter (L), and/or platelet count <100×10^9/L not related to hypersplenism.
- Uncorrected bleeding disorder.
- Any prior or current malignancy.
- Prior HSCT.
- Advanced liver disease.
- A cardiac T2* <10 ms by MRI.
- Any other evidence of severe iron overload that, in the investigator's opinion, warrants exclusion.
- Participation in another clinical study with an investigational drug within 30 days of Screening.
- Any other condition that would render the participant ineligible for HSCT, as determined by the attending transplant physician or investigator.
- Prior receipt of gene therapy.
- Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participant.
- A known and available human leukocyte antigen (HLA) matched family donor.
- Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
Data sourced from ClinicalTrials.gov (NCT03207009). 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.