E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle cell disease (SCD) |
Anemia falciforme |
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E.1.1.1 | Medical condition in easily understood language |
Sickle cell disease (SCD) |
Anemia falciforme |
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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 |
• Valutare l’efficacia di FT-4202 in adolescenti e adulti affetti da AF rispetto al placebo, misurata come miglioramento del contenuto di emoglobina (Hb) • Valutare l’efficacia di FT-4202 rispetto al placebo sul tasso annualizzato di crisi vaso-occlusive (CVO) |
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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 |
• Misurare gli effetti di FT-4202 su misure cliniche e sequele di emolisi • Valutare gli effetti di FT-4202 sulle sequele di CVO • Valutare i cambiamenti nella sensazione di affaticamento dei pazienti con anemia falciforme che assumono 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 |
1) Fornitura del consenso informato 2) Il paziente ha una diagnosi confermata di malattia falciforme 3) Almeno 2 episodi di crisi vaso-occlusive negli ultimi 12 mesi 4) Emoglobina = 5,5 e = 10 g/dl (= 55 e = 100 g/L) durante lo screening 5) I pazienti che assumono idrossiurea devono dimostrare una dose stabile per almeno 90 giorni prima dell'inizio del trattamento in studio 6) Le pazienti di sesso femminile in età fertile devono utilizzare misure contraccettive altamente efficaci, i pazienti di sesso maschile devono essere disposti a utilizzare misure contraccettive di barriera |
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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) |
Condizioni mediche 1) Più di 10 crisi vaso-occlusive negli ultimi 12 mesi 2) Sggetto di sesso femminile che allatta o è incinta 3) Disfunzione epatica caratterizzata da: - Alanina aminotransferasi (ALT) > 4,0 × limite superiore del normale (ULN) - Bilirubina diretta > 3,0 × ULN 4) Soggetto noto come HIV-positivo 5) Infezione attiva da epatite B o C 6) Grave disfunzione renale o in dialisi cronica 7) Storia di malattia cardiaca o polmonare instabile o in deterioramento nei 6 mesi precedenti il consenso, tra cui: - Angina pectoris instabile o infarto miocardico o intervento coronarico elettivo - Insufficienza cardiaca congestizia che richiede l'ospedalizzazione - Aritmie clinicamente significative non controllate - Ipertensione polmonare sintomatica 8) Storia di ictus clinico manifesto nei 2 anni precedenti o qualsiasi storia di emorragia intracranica Terapia precedente/comitante 1) Pazienti che ricevono regolarmente una terapia trasfusionale (RBC) programmata (definita anche trasfusione cronica, profilattica o preventiva) 2) Ricezione o uso di farmaci concomitanti che sono forti induttori o moderati/forte inibitori del CYP3A4/5 entro 2 settimane dall'inizio del trattamento di studio o necessità prevista di tali agenti durante lo studio 3) Uso di voxelotor nei 28 giorni precedenti l'inizio del trattamento dello studio o necessità prevista di questo agente durante lo studio 4) Uso di un antagonista della selectina (es. crizanlizumab o altro anticorpo monoclonale o piccola molecola) entro 28 giorni dall'inizio del trattamento dello studio o necessità prevista di tali agenti durante lo studio 5) Uso di eritropoietina o altro trattamento con fattore di crescita ematopoietico entro 28 giorni dall'inizio del trattamento dello studio o necessità prevista di tali agenti durante lo studio 6) Ricezione di una precedente terapia a base di cellule (es. trapianto di cellule ematopoietiche, terapia di modificazione genica) |
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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 |
• Tasso di risposta dell’Hb alla Settimana 24 (aumento di >1 g/dl [>10 g/l] rispetto al basale) durante il periodo di trattamento in cieco • Tasso di CVO annualizzato durante il periodo di trattamento in cieco di 52 settimane in base alla revisione delle CVO stabilita |
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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 ] |
• Tasso di risposta dell’Hb alla Settimana 24 (aumento di >1 g/dl [>10 g/l] rispetto al basale) durante il periodo di trattamento in cieco: 24 settimane • Tasso di CVO annualizzato durante il periodo di trattamento in cieco di 52 settimane in base alla revisione delle CVO stabilita: 52 settimane |
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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; • Variazione rispetto al basale dell’Hb alla Settimana 24 durante il periodo di trattamento in cieco • Cambiamento delle misurazioni cliniche di laboratorio relative all’AF, rispetto al basale, alla Settimana 24 durante il periodo di trattamento in cieco: o % di reticolociti, o bilirubina non coniugata, e o lattato deidrogenasi (LDH) • Tempo alla prima CVO durante il periodo di trattamento in cieco • Variazione rispetto al basale nei punteggi della scala dell’affaticamento del Sistema informativo per la misurazione degli esiti riferiti dal paziente (PROMIS) alla Settimana 24, durante il periodo di trattamento in cieco |
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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.; • Variaz |
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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 | 3 |
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 | Information not present in EudraCT |
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |