E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects treated with gene therapy drug products in a bluebird bio-sponsored study will be invited to participate in this long-term follow-up study to monitor the safety and efficacy of the drug products. To date, subjects in this study have been treated with bluebird bio gene therapy drug products developed to treat the following indications:
beta-thalassaemia major Sickle cell disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055579 |
E.1.2 | Term | Sickle-cell beta thalassemia |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Monitor the long-term safety and efficacy of gene therapy drug products used in bluebird bio-sponsored clinical studies in treated subjects with hemoglobinopathies
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent for this study by subject, or as applicable, subject’s parent(s)/ legal guardian(s). 2. Previously treated with drug product for therapy of a hemoglobinopathy in a bluebird bio-sponsored clinical study. 3. Able to comply with study requirements
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E.4 | Principal exclusion criteria |
There are no exclusion criteria for this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints include: - Overall survival - All drug product-related adverse events (AEs) through Year 15 postdrug product infusion - All serious adverse events (SAEs) through Year 15 post-drug product infusion - Immune-related AEs - New or worsening hematologic disorders - New or worsening neurologic disorders - Malignancies - Incidence of vector-derived replication-competent lentivirus (RCL), assessed as clinically indicated - The number of subjects with insertional oncogenesis
Pharmacodynamic endpoints: - Vector copy number (VCN) in peripheral blood over time - βA-T87Q-globin expression in peripheral blood over time
Efficacy Endpoints include: For LentiGlobin HPV569 Drug Product-treated subjects: - pRBC transfusion and volume over time - Total Hb levels over time - Use of chelation therapy and therapeutic phlebotomy - Iron burden over time
For beti-cel-treated subjects with TDT: - Proportion of subjects who meet the definition of transfusion independence (TI) at any time and at yearly timepoints - Characterization of TI - Characterization of transfusion reduction (TR) - Weighted average nadir Hb from 6 months post-drug product infusion through last follow-up as compared to the weighted average nadir Hb during the 2 years prior to parent study enrollment - Unsupported total Hb levels over time - Iron burden over time and change in baseline - Use of chelation therapy and therapeutic phlebotomy - Measures of dyserythropoiesis over time - Health-related quality of life (HRQoL) over time
For bb1111-treated with subjects with SCD: - Assessment of hematological parameters over time - Change from baseline in hemolysis markers - Change from baseline in markers of iron stores - Change from baseline in markers of stress erythropoiesis/anemia - Annualized pRBC transfusion volume (mL/kg/year) and frequency (number/year) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Follow-up visits are scheduled every 6 months through Year 5 (Month 60) post-transplant, and then annually thereafter through Year 15 post-transplant. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
France |
Germany |
Greece |
Italy |
Thailand |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 13 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 13 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |