E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Sickle cell disease is a chronic, inherited blood disorder that impacts haemoglobin, a protein found in red blood cells (RBCs) that carries oxygen throughout the body. |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
The objective of this open-label extension (OLE) study is to assess the
long-term safety and treatment effect of voxelotor in participants who have completed
treatment in study GBT440-031, using the following parameters:
• Safety based upon AEs, clinical laboratory tests, physical examinations
(PE) andother clinical measures.
• Frequency of sickle cell-related complications
• Hemolytic anemia as measured by hematological laboratory
parameters (e.g.hemoglobin, reticulocytes and unconjugated bilirubin). |
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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. Male or female study participants with SCD who participated and received study treatment in Study GBT440-031.
Note: Participants in GBT440-031 who discontinued study drug due to an AE, but who remained on study may be eligible for treatment in this study provided the AE does not pose a risk for treatment with Voxelotor.
2. Females of child-bearing potential are required to have a negative urine pregnancy test prior to dosing on Day 1.
3. Female participants of child-bearing potential must use highly effective methods of contraception to 30 days after the last dose of study drug. Male participants must continue to use barrier methods of contraception to 30 days after the last dose of study
drug.
4. Participant has provided written informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained). |
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E.4 | Principal exclusion criteria |
1. Female who is breast-feeding or pregnant.
2. Participant withdrew consent from Study GBT440-031.
3. Participant was lost to follow-up from Study GBT440-031.
4. Participant requiring chronic dialysis.
5. Any medical, psychological, safety, or behavioral conditions, which, in the opinion of the Investigator, may confound safety interpretation, interfere with compliance, or preclude informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Safety endpoints include AEs, clinical laboratory tests, physical
examinations and other clinical measures.
2. Frequency of SCD-related complications of long-term dosing with Voxelotor.
3. Hemolytic anemia as measured by hematological laboratory parameters (e.g.hemoglobin, reticulocytes and unconjugated bilirubin). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Weeks 4, 8, 12, 24, 48, then Q24 weeks until EOS visit (28-35 days after last dose for participants who withdraw early or anytime after patient obtains commerical Voxelotor for participants who complete the study per protocol) |
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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 | No |
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 |
randomisation - only for one patient sub-group |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 |
Egypt |
Oman |
Canada |
Kenya |
Lebanon |
United Kingdom |
United States |
France |
Italy |
Netherlands |
Türkiye |
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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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Participants may receive study drug as long they continue to receive clinical benefit which outweighs risk as determined by the Investigator and/or until the participant has access to voxelotor from an alternative source (i.e., commercialization or through a managed access program). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 25 |