Transfusion-dependent Beta-Thalassemia
Conditions
Brief summary
This is a multi-center, long-term safety and efficacy follow-up study for subjects with transfusion-dependent β-thalassemia (TDT) who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored parent clinical studies. After completing the parent clinical studies (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in this study.
Interventions
Genetic: No interventional drug product utilized in this follow-up study Participants received a single IV infusion of LentiGlobin BB305 Drug Product in the parent studies. Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term effects of autologous transplant are conducted in this study.
Sponsors
Genetix Biotherapeutics Inc.
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent for this study by subjects, or as applicable, subject's parent(s)/legal guardian(s) * Treated with drug product for therapy of transfusion-dependent β-thalassemia in a bluebird bio-sponsored clinical study
Exclusion criteria
* There are no
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number of subjects with malignancies | Up to 15 years post-drug product infusion |
| The number of subjects with immune-related AEs | Up to 15 years post-drug product infusion |
| The number of subjects with new or worsening hematologic disorders | Up to 15 years post-drug product infusion |
| The number of subjects with new or worsening neurologic disorders | Up to 15 years post-drug product infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Transfusion Independence | Up to 15 years post-drug product infusion | — |
| Weighted average Hb during Transfusion Independence | Up to 15 years post-drug product infusion | — |
| Change in annualized pRBC transfusion volume (among subjects who achieved TI), from 6 months post-drug product infusion (parent study) through last follow-up | Up to 15 years post-drug product infusion | Reduction in annualized pRBC transfusion volume (mL/kg/year) from 6 months post-drug product infusion (parent study) through last follow-up of at least 50%, 60%, 75%, 90%, or 100% as compared to the annualized pRBC transfusion volume during the 2 years prior to parent study enrollment |
| Annualized pRBC transfusion volume, from 6 months post-drug product infusion (parent study) through last follow-up | Up to 15 years post-drug product infusion | Annualized pRBC transfusion volume (mL/kg/year from 6 months post-drug product infusion (parent study) through last follow-up as compared to the annualized pRBC transfusion requirements during the 2 years prior to parent study enrollment |
| pRBC transfusion frequency, from 6 months post-drug product infusion (parent study) through last follow-up | Up to 15 years post-drug product infusion | Annualized pRBC frequency (number/year) from 6 months post-drug product infusion (parent study) through last follow-up as compared to the annualized pRBC transfusion requirements during the 2 years prior to parent study enrollment |
| Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303) | Up to 15 years post-drug product infusion | — |
| Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up | Up to 15 years post-drug product infusion | — |
| Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up | Up to 15 years post-drug product infusion | Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up as compared to the weighted average nadir Hb during the 2 years prior to parent study enrollment |
| Change from Baseline in patient reported outcome (PRO) as assessed by Pediatric Quality of Life Inventory (PedsQL | 5 years post-drug product infusion | — |
| Unsupported total Hb levels over time through last follow-up | Up to 15 years post-drug product infusion | Unsupported total Hb level is defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date. |
| Proportion of subjects with unsupported total Hb levels ≥ 10 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 | Up to 15 years post-drug product infusion | — |
| Proportion of subjects with unsupported total Hb levels ≥ 11 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 | Up to 15 years post-drug product infusion | — |
| Proportion of subjects with unsupported total Hb levels ≥ 12 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 | Up to 15 years post-drug product infusion | — |
| Proportion of subjects with unsupported total Hb levels ≥ 13 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 | Up to 15 years post-drug product infusion | — |
| Proportion of subjects with unsupported total Hb levels ≥ 14 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 | Up to 15 years post-drug product infusion | — |
| Liver iron content (LIC) by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Change from parent study baseline in LIC by MRI/SQUID over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Cardiac T2* by MRI over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Change from parent study baseline in cardiac T2* by MRI over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Serum ferritin over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Change from parent study baseline in serum ferritin over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Number of subjects who stopped iron chelation post-DP infusion | Up to 15 years post-drug product infusion | Defined as subjects who stopped iron chelation or never restarted chelation after DP infusion. |
| Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion | Up to 15 years post-drug product infusion | — |
| Time from stopping chelation to last follow-up | Up to 15 years post-drug product infusion | Among subjects that never restart chelation after DP infusion. |
| Proportion of subjects using phlebotomy therapy post-drug product infusion | Up to 15 years post-drug product infusion | — |
| Annualized frequency of phlebotomy therapy usage | Up to 15 years post-drug product infusion | Annualized frequency of phlebotomy therapy usage is defined as the number of procedures per year, calculated from DP infusion through last follow-up. |
| Reticulocyte counts over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Change from Baseline in reticulocyte counts at yearly timepoints through last follow-up | 15 years post-drug product infusion | Baseline defined as value closest, but prior to, conditioning in parent study. |
| Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up | Up to 15 years post-drug product infusion | — |
| Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y) | 5 years post-drug product infusion | — |
| Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L) | 5 years post-drug product infusion | — |
| βA-T87Q-globin expression | Up to 15 years post-drug product infusion | Median (min, max) βA-T87Q-globin expression |
| Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36) | 5 years post-drug product infusion | — |
| Change From Baseline in PRO as assessed by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | 5 years post-drug product infusion | — |
| Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI) | Up to 15 years post-drug product infusion | Proportion of subjects who achieved TI, defined as a weighted average Hb ≥ 9 g/dL without any packed red blood cell (pRBC) transfusions for a continuous period of ≥ 12 months at any time after drug product infusion in parent study and/or Study LTF-303 |
| Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints | Up to 15 years post-drug product infusion | Proportion of subjects treated with beti-cel who achieved TI at yearly timepoints including Year 5, Year 10, and Year 15 post-drug product infusion, and at last follow-up |
| Time from drug product infusion to achievement of Transfusion Independence (in parent study or Study LTF-303) | Up to 15 years post-drug product infusion | — |
Countries
Australia, France, Germany, Greece, Italy, Thailand, United Kingdom, United States
Outcome results
None listed