E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with sickle-cell disease 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. |
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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 | 10040648 |
E.1.2 | Term | Sickle cell SC disease |
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 |
• Evaluate 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 sickle cell disease (SCD)
• Evaluate 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. Treated with drug product for therapy of sickle cell disease 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) |
Primary Efficacy Endpoint:
• Non-transfused total hemoglobinover time
Pharmacodynamic Endpoints:
• Vector copy number (VCN) in peripheral blood over time post-drug product infusion
• βA-T87Q-globin expression in peripheral blood over time post-drug product infusion |
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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) |
Secondary Safety Endpoint:
• Overall survival
• All drug product-related adverse events (AEs) through Year 15 post-drug product infusion
• All serious adverse events (SAEs) through Year 15 post-drug product infusion (regardless of relatedness to drug product).
• Serious or non-serious immune-related AEs (e.g., autoimmune disorders, graft-versus-host disease, opportunistic infections, HIV) and new or worsening hematologic or neurologic disorders or malignancies
• Incidence of insertional mutagenesis leading to leukemia
Secondary Efficacy Endpoints:
• Assessment of the following over time:
− non-transfused total Hb ≥10g/dL
− HbS percentage of non-transfused total Hb
− HbS percentage of non-transfused total Hb ≤70%, ≤60%, ≤50%
− HbAT87Q percentage of non-transfused total Hb
− HbAT87Q percentage of non-transfused total Hb ≥30%, ≥40%, ≥50%
− non-HbS percentage of non-transfused total Hb
• Change from parent study baseline in hemolysis markers
• Change from parent study baseline in markers of iron stores
• Change from parent study baseline in markers of stress erythropoiesis/anemia
• 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
• Change in SCD complications which may include but are not limited to: vaso-occlusive events (VOC, ACS, priapism, hepatic sequestration, splenic sequestration), new or worsening osteonecrosis, or severe leg ulcers; retinopathy, change from baseline in renal function, cardiac-pulmonary function |
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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 | No |
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 | No |
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 |
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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 |