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 beta-thalassaemia major |
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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 | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10082045 |
E.1.2 | Term | Beta-thalassemia trait |
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 for long-term safety of the gene therapy drug product (i.e., the “drug product”) used in bluebird bio-sponsored clinical studies (i.e., the “parent studies”) in treated subjects with transfusion-dependent β-thalassemia (TDT) • Monitor for long-term efficacy of the drug product |
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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) 2.1. Treated with drug product for therapy of transfusion-dependent β-thalassemia in a bluebird bio-sponsored clinical study |
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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) |
• The number of subjects with malignancies • The number of subjects with immune-related AEs (e.g., autoimmune disorders, GVHD, opportunistic infections, HIV) • The number of subjects with new or worsening hematologic disorders • The number of subjects with new or worsening neurologic disorders |
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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) |
• βA-T87Q-globin expression in peripheral blood over time post-drug product infusion through last follow-up, including Year 5, Year 10, and Year 15 (TI), defined as a weighted average Hb ≥ 9 g/dL without any 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 who meet the definition of TI at yearly timepoints including Year 5, Year 10, and Year 15 post-drug product infusion, and at last follow-up • Characterization of TI: o Time from drug product infusion to achievement of TI (in parent study or Study LTF-303) o Duration of TI o Weighted average Hb during TI • Characterization of transfusion reduction (TR): o 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 o Annualized pRBC transfusion volume (mL/kg/year) and 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 o Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303) o Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up • 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 • Unsupported total Hb levels over time through last follow-up, including Year 5, Year 10, and Year 15 • Unsupported total Hb levels ≥ 10 g/dL, ≥ 11 g/dL, ≥ 12 g/dL, ≥ 13 g/dL, and ≥ 14 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15 • Iron burden over time and change from parent study baseline in iron burden at yearly timepoints through last follow-up, as measured by: o Liver iron content by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) as available o Cardiac T2* by MRI as available o Serum ferritin • Chelation therapy use, including time from last use of chelation therapy to last follow-up and absence of chelation use for at least 6 months post-drug product infusion in parent study and/or Study LTF-303 • Therapeutic phlebotomy use, including annualized frequency • Measures of dyserythropoiesis over time as compared to parent study baseline, assessed by the following parameters: o Reticulocytes o Nucleated RBCs • Health-related quality of life (HRQoL) over time as compared to parent study baseline, using the following validated tools as available and as appropriate: o Pediatric Quality of Life Inventory (PedsQL) o EuroQol-5D (EQ-5D; youth version, EQ-5D-Y) o Short Form-36 (SF-36) v2 o Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) |
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E.5.2.1 | 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.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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
Thailand |
United States |
France |
Germany |
Greece |
Italy |
United Kingdom |
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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 |