E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
sickle cell disease (SCD) |
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E.1.1.1 | Medical condition in easily understood language |
sickle cell disease (SCD) |
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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 |
• To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)
• To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate |
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E.2.2 | Secondary objectives of the trial |
• To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis
• To evaluate the effects of FT-4202 on the sequelae of VOC
• To assess changes in fatigue of sickle cell patients taking FT-4202 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Provision of consent
2) Patient has a confirmed diagnosis of sickle cell disease
3) At least 2 episodes of vaso-occlusive crises in the past 12 months
4) Hemoglobin ≥ 5.5 and ≤ 10 g/dL (≥ 55 and ≤ 100 g/L) during screening
5) Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment
6) Female patients of childbearing potential must use highly effective methods of contraception, male patients are willing to use barrier methods of contraception
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E.4 | Principal exclusion criteria |
Medical Conditions
1) More than 10 vaso-occlusive crises within the past 12 months
2) Female who is breast feeding or pregnant
3) Hepatic dysfunction characterized by:
- Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN)
- Direct bilirubin > 3.0 × ULN
4) Known HIV positive
5) Active hepatitis B or hepatitis C infection
6) Severe renal dysfunction or on chronic dialysis
7) History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
- Unstable angina pectoris or myocardial infarction or elective coronary intervention
- Congestive heart failure requiring hospitalization
- Uncontrolled clinically significant arrhythmias
- Symptomatic pulmonary hypertension
8) History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
Prior/Concomitant Therapy
1) Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
2) Receiving or use of concomitant medications that are strong inducers or moderate/strong inhibitors of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study
3) Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
4) Use of a selectin antagonist (eg, crizanlizumab or other monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study
5) Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
6) Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy)
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E.5 End points |
E.5.1 | Primary end point(s) |
• Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period
• Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Hemoglobin response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period [ Time Frame: 24 Weeks ]
2. Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review [ Time Frame: 52 Weeks ] |
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E.5.2 | Secondary end point(s) |
• Change from baseline in Hb at Week 24 during the blinded treatment period
• Change in SCD-related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period in:
o % reticulocytes,
o Unconjugated bilirubin, and
o Lactate dehydrogenase (LDH)
• Time to first VOC during the blinded treatment period
• Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 24 during the blinded treatment period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Change from baseline in hemoglobin at W24 during the blinded treatment period [Time Frame: 24 Weeks]
2. Change in SCD related clinical lab measurements from baseline at W24 during the blinded treatment period [Time Frame: 24 Weeks]
- % reticulocytes; Unconjugated bilirubin; Lactate dehydrogenase
3. Time to first vaso-occlusive during the blinded treatment period [Time Frame: 52 Weeks]
4. Change from baseline in PROMIS) Fatigue Scale at W24 during the blinded treatment period [Time Frame: 24 Weeks]
Adult patients (18 to 65) will complete the PROMIS® Item Bank v.1.0 - Fatigue - Short Form 7a. Adolescent patients (12 to 17) will complete the PROMIS® Item Bank v2.0 - Fatigue - Short Form 10a. Responses are graded on a score of 1 to 5 with a higher score indicating a worse outcome. |
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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 | Yes |
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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 29 |
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 |
Canada |
United States |
France |
Germany |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |