E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate or severe cGVHD |
cGVHD moderato o grave |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate or severe chronic Graft Versus Host Disease |
la malattia cronica del trapianto contro l’ospite moderata o grave |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066261 |
E.1.2 | Term | Chronic graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072160 |
E.1.2 | Term | Chronic graft versus host disease in liver |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072158 |
E.1.2 | Term | Chronic graft versus host disease in intestine |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072159 |
E.1.2 | Term | Chronic graft versus host disease in skin |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
|
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 |
Part 1: To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.
Part 2: To compare the efficacy of itacitinib versus placebo in combination with corticosteroids as initial treatment for moderate or severe cGVHD. |
Parte 1: Identificare una dose appropriata di itacitinib in combinazione con corticosteroidi come trattamento iniziale per la malattia cronica del trapianto contro l’ospite (cGVHD) moderata o grave. Parte 2: Confrontare l’efficacia di itacitinib rispetto a placebo in combinazione con corticosteroidi come trattamento iniziale per la cGVHD moderata o grave. |
|
E.2.2 | Secondary objectives of the trial |
Part 1:
- To evaluate the PK of itacitinib when administered in combination with corticosteroids in the study population.
- To estimate efficacy outcomes.
Part 2:
- To compare changes in health-related quality of life.
- To compare additional efficacy outcomes between treatment groups.
- To evaluate the PK of itacitinib in combination with corticosteroids in 1L cGVHD.
- To evaluate the safety and tolerability of study treatment across the 2 treatment cohorts. |
Parte 1: - Valutare la farmacocinetica (PK) di itacitinib quando somministrato in combinazione con corticosteroidi nella popolazione dello studio. - Stimare gli esiti di efficacia. Parte 2: - Confrontare le variazioni nella qualità della vita correlata alla salute. - Confrontare ulteriori esiti di efficacia tra i gruppi di trattamento. - Valutare la PK di itacitinib in combinazione con corticosteroidi nel trattamento di 1L della cGVHD. - Valutare la sicurezza e la tollerabilità del trattamento dello studio nelle 2 coorti di trattamento. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, aged 18 years or older inclusive at the time of signing the ICF. 2. Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria : a. Moderate cGVHD: At least 1 organ (except lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1. b. Severe cGVHD: At least 1 organ with a score of 3, or lung score of 2 or 3. Note: Candidates who transition from active aGVHD to cGVHD without tapering off of corticosteroids (< 0.25 mg/kg per day) ± CNI are also eligible. 3. Underwent allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative or reduced intensity conditioning are eligible. 4. KPS score = 60%. 5. Evidence of myeloid and platelet engraftment, that is, ANC = 1.0 × 109/L and platelet count = 25 × 109/L. Note: Use of growth factor supplementation and transfusion support is allowed during the study; however, transfusion to reach a minimum platelet count for inclusion is not allowed within the 7 days before the screening laboratory assessment. |
1. Maschio o femmina, di età compresa tra 18 anni o superiore al momento della firma dell'ICF. 2. cGVHD attivo, clinicamente diagnosticato, moderato o grave per Criteri di consenso NIH: a. Moderata cGVHD: almeno 1 organo (eccetto il polmone) con un punteggio di 2, 3 o più organi coinvolti con un punteggio di 1 in ciascun organo, o punteggio polmonare di 1. b. Grave cGVHD: almeno 1 organo con un punteggio di 3, o punteggio polmonare di 2 o 3. Nota: anche i candidati che passano da aGVHD attivo a cGVHD senza riduzione dei corticosteroidi (<0,25 mg / kg al giorno) ± CNI sono idonei. 3. Sottoposto allo-HCT da qualsiasi donatore di tipo HLA (donatore correlato o non correlato con qualsiasi grado di corrispondenza HLA) utilizzando qualsiasi fonte di trapianto (midollo osseo, cellule staminali del sangue periferico o sangue del cordone ombelicale). Sono eleggibili i riceventi di condizionamento mieloablativo, non mieloablativo o di intensità ridotta. 4. Punteggio KPS = 60%. 5. Prove di attecchimento di mieloide e piastrine, cioè ANC = 1.0 × 109 / L e conta piastrinica = 25 × 109 / L. Nota: l'uso del supplemento del fattore di crescita e del supporto trasfusionale è consentito durante lo studio; tuttavia, la trasfusione per raggiungere un numero minimo di piastrine per l'inclusione non è consentita nei 7 giorni precedenti la valutazione del laboratorio di screening |
|
E.4 | Principal exclusion criteria |
1. Has received more than 1 prior allo-HCT. Prior autologous HCT is allowed. 2. Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD. 3. Has received any other systemic treatment for cGVHD, including ECP. Prior and concomitant use of CNIs as well as topical/inhaled steroids is acceptable. 4. Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for aGVHD are eligible only if they achieved CR or PR. 5. cGVHD occurring after a nonscheduled DLI administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible. |
1. Ha ricevuto più di 1 precedente a HCT. È consentito l'HCT autologo precedente. 2. Ha ricevuto più di 3 giorni / 72 ore di trattamento con corticosteroidi sistemici per cGVHD. 3. Ha ricevuto qualsiasi altro trattamento sistemico per cGVHD, incluso ECP. L'uso precedente e concomitante di CNI e steroidi per uso topico / inalatorio è accettabile. 4. Trattamento precedente con un inibitore entro 8 settimane prima della randomizzazione. I partecipanti che hanno ricevuto un inibitore JAK per aGVHD hanno diritto solo se hanno raggiunto CR o PR. 5. cGVHD che si verifica dopo un DLI non programmato somministrato per il trattamento preventivo della recidiva della malignità. I partecipanti che hanno ricevuto un DLI programmato come parte della loro procedura di trapianto e non per la gestione della recidiva di malignità sono ammissibili. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: DLT data through Day 28 and additional data from clinical safety and laboratory assessments.
Part 2: Response rate at Month 6, defined as the proportion of participants demonstrating a CR or PR at Month 6. |
Parte 1: Dati sulla tossicità dose-limitante (DLT) fino al Giorno 28 e ulteriori dati ottenuti dalle valutazioni cliniche di sicurezza e di laboratorio. Parte 2: Tasso di risposta al Mese 6, definito come la proporzione di partecipanti che dimostrano una CR o una PR al Mese 6. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: through Day 28
part 2: at Month 6 |
Parte 1: fino al 28 ° giorno parte 2: al mese 6 |
|
E.5.2 | Secondary end point(s) |
Part 1: - Cmax, Cmin, Tmax, AUC0-t, and Cl/F. - Response rate at Month 3, 6, and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - Time to response, defined as the interval between randomization and first response. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants with = 50% reduction in daily corticosteroid dose at Day 180. - Proportion of participants successfully tapered off all corticosteroids at Day 180. - Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses. - Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse.
Part 2: - Changes in symptom scores using the LSS, QOL-SF-36 v2, and EQ-5D-3L, PGIC, and PGIS. - Response rate at Month 3 and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants with = 50% reduction in daily corticosteroid dose at Day 180. - Proportion of participants successfully tapered off all corticosteroids at Day 180. - Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses. - Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse. - Cmin in all participants; Cmax, Tmax, AUC0-t, and Cl/F, data permitting. - Data from clinical safety assessments (eg, AEs, infections) will be listed and tabulated. |
Parte 1: - Cmax, Cmin, Tmax, AUC0-t, and Cl/F. - Response rate at Month 3, 6, and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - Time to response, defined as the interval between randomization and first response. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants with = 50% reduction in daily corticosteroid dose at Day 180. - Proportion of participants successfully tapered off all corticosteroids at Day 180. - Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses. - Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse.
Part 2: - Changes in symptom scores using the LSS, QOL-SF-36 v2, and EQ-5D-3L, PGIC, and PGIS. - Response rate at Month 3 and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint. - DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy. - OS, defined as the interval between the date of randomization and the date of death due to any cause. - NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease. - Proportion of participants with = 50% reduction in daily corticosteroid dose at Day 180. - Proportion of participants successfully tapered off all corticosteroids at Day 180. - Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses. - Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse. - Cmin in all participants; Cmax, Tmax, AUC0-t, and Cl/F, data permitting. - Data from clinical safety assessments (eg, AEs, infections) will be listed and tabulated. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part 1: Month 3, 6 and 12
Part 2: Month 3, 6, 12 |
Part 1: Month 3, 6 and 12 Part 2: Month 3, 6, 12 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Parte 1: randomizzata, in aperto; Parte 2: randomizzata, in doppio cieco, controllata con placebo |
Part 1: randomized, open-label; Part 2: randomized, double-blind, placebo-controlled |
|
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 | 2 |
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 | 19 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 |
Israel |
United States |
Austria |
Belgium |
Czechia |
Denmark |
France |
Germany |
Greece |
Hungary |
Italy |
Poland |
Spain |
Sweden |
United Kingdom |
|
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
|
The study will end once all randomized patients have reached Month 36 or discontinued the study early due to any reason. |
Lo studio terminerà quando tutti i pazienti randomizzati avranno raggiunto il mese 36 o interrotto anticipatamente lo studio per qualsiasi motivo. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |