| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin’s Lymphoma |
| Pazienti con linfoma diffuso a grandi cellule B recidivante e/o refrattario e altre forme di linfoma non-Hodgkin. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) or other forms of non-Hodgkin's lymphoma (NHL) who have stopped responding or have failed to respond to current cancer treatments. |
Pazienti con Linfoma Diffuso a Grandi Cellule B (DBLCL) o alter forme di Linfoma Non-Hodking (NHL) che hanno smesso di rispondere o non hanno risposto agli attuali trattamenti oncologici.
|
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029600 |
| E.1.2 | Term | Non-Hodgkin's lymphoma recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 24.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10067070 |
| E.1.2 | Term | Follicular B-cell non-Hodgkin's lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10026800 |
| E.1.2 | Term | Mantle cell lymphoma recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10076596 |
| E.1.2 | Term | Marginal zone lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10026801 |
| E.1.2 | Term | Mantle cell lymphoma refractory |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10012822 |
| E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029601 |
| E.1.2 | Term | Non-Hodgkin's lymphoma refractory |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10012821 |
| E.1.2 | Term | Diffuse large B-cell lymphoma recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
- Determine the safety and tolerability of the proposed Debio 1562 dose regimens in combination with rituximab
- Determine the anti-tumor activity of the proposed Debio 1562 dose regimens in combination with rituximab |
- Determinare la sicurezza e la tollerabilità dei regimi di somministrazione proposti di Debio 1562 in combinazione con rituximab
- Determinare l’attività antitumorale dei regimi di somministrazione proposti di Debio 1562 in combinazione con rituximab
|
|
| E.2.2 | Secondary objectives of the trial |
- Characterize the PK of Debio 1562 in combination with rituximab
- Determine time to event outcomes [progression-free survival (PFS), time to response, duration of response (DOR), and overall survival (OS)]
- Assess the immunogenicity of Debio 1562 (anti-drug antibodies, ADA) when administered in combination with rituximab |
- Descrivere la farmacocinetica (PK) di Debio 1562 in combinazione con rituximab
- Determinare gli outcome di tipo “tempo all’evento” (sopravvivenza libera da progressione [Progression-Free Survival, PFS], tempo alla risposta, durata della risposta [Duration of Response, DoR] e sopravvivenza globale [Overall Survival, OS])
- Valutare l’immunogenicità di Debio 1562 (anticorpi anti-farmaco [Anti-Drug Antibody, ADA]) in cos-omministrazione con rituximab
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) For Part 1 of the study, patients must have histopathologically confirmed diagnosis of relapsed and/or refractory DLBCL, FL, MZL/MALT, MCL, or other Sponsor approved NHL subtypes according to the World Health Organization (WHO) classification 2008 for which standard measures do not exist or are no longer effective.
2) For Part 2 and Part 3 of the study, patients must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Patients will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following patients with relapsed DLBCL will be enrolled:
i. Patients who received only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but whom are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT)
ii. Patients who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy
3) Patients must have received no more than six prior treatment regimens. Prior treatment with an anti- CD20 agent, either alone or in combination, is allowed.
4) Patients must be = 18 years.
5) Patients must have ECOG Performance Status 0-2.
6) Patients must meet the following laboratory criteria:
- Absolute neutrophil count (ANC) = 1.0 x 10^9/L (1000/mm^3),
- Platelet count = 50 x 10^9/L (50,000/mm^3; patients must not have been transfused within 10 days previous blood drawn for laboratory assessment),
-Patients receiving therapeutic anticoagulation are eligible provided their anticoagulation parameters are within range (e.g. International Normalized Ratio [INR] 2-3 on Coumadin if applicable) and they have no history of = Grade 2 bleeding while on anticoagulatioin therapy.
-For patients receiving therapeutic doses of anticoagulation: Platelet count = 100 x 10^9/L (100,000/mm^3; must not have been transfused wihtin previous 10 days)
- Hemoglobin = 8.0 g/dL (may have been transfused),
- Serum creatinine = 2.0 x upper limit of normal (ULN) or 24-hour creatinine clearance of = 60 mL/minute,
- AST = 2.5 x ULN; ALT = 2.5 x ULN and
- Total bilirubin = 1.5 x ULN; patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin = 3.0 x ULN.
7) Patients must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma (Cheson 2014).
8) Patients who are Hepatitis B surface antygen (HBsAg) + (must be PCR negative) who are taking antivirals are allowed to enroll.
9) Male patients and female patients of child bearing potential participating in the study must agree to use two highly effective methods of contraception throughout this study and for at least 12 weeks after the last dose of Debio 1562 and 12 months after the last dose of rituximab. Examples of acceptable birth control methods include but are not limited to the following methods: (e.g, oral, parenteral, or implantable hormonal contraceptive; tubal ligation; intra-utérine device; barrier contraceptive with spermicide; partner's latex condom or vasectomy).
10) Patients must be willing and able to sign the informed consent form and comply with the study protocol.
11) Patients must be willing to provide a fresh or archived tumor biopsy. If archived tissue is provided, it must have obtained wihtin one year of the screening period and the tumor must not have transformed during that time. If transformation occured within one year from starting study treatment, the tumor biopsy must be from after the latest transformation; otherwise a fresh biopsy must be collected. |
1) Per la Parte 1 dello studio, i pazienti devono avere una diagnosi con conferma istopatologica di malattia recidivante e/o refrattaria (R/R), ossia DLBCL, FL, MZL/MALT, MCL o altro sottotipo di NHL approvato dal promotore, in base alla classificazione dell’OMS del 2008, per la quale non esistano terapie standard o queste non siano più efficaci.
2) Per la Parte 2 e la Parte 3 dello studio, i pazienti devono avere una diagnosi con conferma istopatologica e clinica di DLBCL recidivante. I pazienti verranno considerati affetti da malattia recidivante se hanno mostrato una risposta della durata minima di 24 settimane dopo la prima linea di terapia. Verranno arruolati pazienti affetti da DLBCL recidivante con le seguenti caratteristiche:
i. Pazienti che abbiano ricevuto una sola linea di terapia precedente e abbiano ottenuto una risposta completa (Complete Response, CR) oppure una risposta parziale (Partial Response, PR) per un periodo di almeno 24 settimane (a partire dall’ultimo giorno dell’ultimo ciclo) dopo la prima linea di terapia, ma che non siano idonei per chemioterapia ad alte dosi con trapianto autologo di cellule staminali (High Dose chemotherapy with Autologous Stem Cell Transplantation, HD-ASCT)
ii. Pazienti che abbiano ricevuto più di una linea di terapia precedente (compresa HD-ASCT) e abbiano ottenuto una risposta (CR o PR) per un periodo di almeno 8 settimane (a partire dall’ultimo giorno dell’ultimo ciclo) dopo l’ultima linea di terapia .
3) I pazienti devono aver ricevuto non più di sei regimi terapeutici precedenti. È consentito il precedente trattamento con un agente anti-CD20, in monoterapia o in combinazione.
4) I pazienti devono avere un’età =18 anni.
5) I pazienti devono avere uno stato funzionale ECOG 0-2.
6) I pazienti devono soddisfare i seguenti criteri di laboratorio:
• Conta assoluta dei neutrofili (Absolute Neutrophil Count, ANC) =1,0 x 109/l (1000/mm3)
• Conta piastrinica =50 x 109/l (50.000/mm3; i pazienti non devono essersi sottoposti a trasfusioni nei 10 giorni che precedono il prelievo ematico per le analisi di laboratorio)
• I pazienti in terapia anticoagulante sono idonei a partecipare, a condizione che i loro parametri di anticoagulazione rientrino nella norma (ad es. International Normalized Ratio [INR] 2-3 per i pazienti in terapia con Coumadin, se applicabile) e che non presentino all’anamnesi episodi di sanguinamento di Grado =2 durante terapia anticoagulante
• Per i pazienti in terapia anticoagulante: conta piastrinica =100 x 109/l (100.000/mm3; non devono essersi sottoposti a trasfusioni nei 10 giorni precedenti)
• Emoglobina =8,0 g/dl (possono essersi sottoposti a trasfusioni)
• Creatinina sierica =2,0x il limite superiore di normalità (Upper Limit of Normal, ULN) oppure clearance della creatinina nelle 24 ore =60 ml/minuto
• AST =2,5x l’ULN; ALT =2,5x l’ULN e
• Bilirubina totale =1,5x l’ULN; i pazienti con diagnosi documentata di sindrome di Gilbert sono idonei se i valori di bilirubina totale sono =3,0x l’ULN. |
|
| E.4 | Principal exclusion criteria |
1) Patients with a diagnosis of CLL or SLL
2) For Part 2 and Part 3 of the study, patients with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment).
3) For Part 2 and Part 3 of the study, patients that are eligible to undergo first time HD-ASCT.
4) For Part 2 and Part 3 of the study, patients with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification.
5) The following exclusions, with regard to prior therapy apply:
- Not recovered from prior chemotherapy or radiation as per Investigator’s judgment.
- Anti-CD20 monoclonal antibody therapy within 14 days of starting study treatment.
- Prior therapy with other anti-CD37-targeting therapy.
- Radioimmunotherapy within two months prior to starting study treatment.
- Small molecule anti-cancer therapeutic agent, and all investigational agents within 5 x t½ or 14 days whichever is shorter.
- Allogeneic stem cell transplantation in the safety run-in period.
- Chronic, systemic treatment with corticosteroids unless the dose has been stable for >7 days and is equivalent to = 10 mg of prednisone per day.
- Patients who have not recovered from prior surgery. Patients must have recovered or stabilized from the side effects of any major or minor surgical procedures prior to study treatment.
6) Patients who have had a prior anaphylactic or other severe infusion reaction such that the patient is unable to tolerate antibody administration.
7) Patients who have known central nervous system, meningeal, or epidural disease including brain metastases.
8) Patients who have received or are to receive vaccination with live viruses within 30 days of Cycle 1 Day1.
9) Impaired cardiac function or clinically significant cardiac disease such as:
- New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy;
- Unstable angina pectoris = 6 months prior to starting study drug;
- Acute myocardial infarction = 6 months prior to starting study drug; or
- Other clinically significant heart disease e.g., = grade 3 hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen.
10) Patients with = Grade 2 peripheral neuropathy.
11) Patients with active hepatitis A, B or C infection.
12) Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, psychiatric illness that would limit compliance with study requirements, active autoimmune disease requiring immunosuppressive therapy, severe immune deficiency.
13) Known diagnosis of human immunodeficiency virus (HIV) infection.
14) Patients with a concurrent primary malignancy that requires treatment or that would confound the disease response interpretation for the disease under study.
15) WCBP who are pregnant or breast feeding.
|
1) Pazienti con diagnosi di CLL o linfoma linfocitico a piccole cellule (Small Lymphocytic Lymphoma, SLL).
2) Per la Parte 2 e la Parte 3 dello studio, pazienti con DLBCL primitivo refrattario (definito come progressione di malattia entro 24 settimane dalla prima linea di trattamento).
3) Per la Parte 2 e la Parte 3 dello studio, pazienti idonei a sottoporsi per la prima volta a HD-ASCT.
4) Per la Parte 2 e la Parte 3 dello studio, pazienti con FL R/R, MZL/MALT, MCL - o qualunque altro sottotipo di NHL - in base alla classificazione dell’OMS
5) Si applicano i seguenti criteri di esclusione relativi alle precedenti terapie:
• Pazienti che non si siano ripresi da precedente chemioterapia o radioterapia, in base alla valutazione dello sperimentatore.
• Terapia con anticorpi monoclonali anti-CD20 nei 14 giorni precedenti l’inizio dell’assunzione del trattamento dello studio.
• Precedente trattamento con altra terapia mirata anti-CD37.
• Radioimmunoterapia nei due mesi precedenti l’inizio dell’assunzione del trattamento dello studio.
• Agenti oncologici a piccola molecola e qualunque farmaco sperimentale entro 5 x t1/2 o 14 giorni, a seconda di quale intervallo sia più breve.
• Trapianto allogenico di cellule staminali durante il periodo del run-in di sicurezza
• Terapia sistemica cronica con corticosteroidi, eccetto in caso di dose stabile per >7 giorni ed equivalente a =10 mg/die di prednisone.
• Pazienti che non si siano ripresi da precedente intervento chirurgico. I pazienti dovranno essersi ripresi dagli effetti indesiderati di qualunque procedura di chirurgia maggiore o minore o essere stabili prima dell’assunzione del trattamento dello studio.
6) Pazienti nei quali si siano verificate in precedenza reazioni anafilattiche o altre gravi reazioni all’infusione, in conseguenza delle quali non siano in grado di tollerare la somministrazione di anticorpi.
7) Pazienti con malattia nota a carico del sistema nervoso centrale, delle meningi o dello spazio epidurale, comprese le metastasi cerebrali.
8) Pazienti nei quali siano stati somministrati o sia prevista la somministrazione di vaccini vivi nei 30 giorni precedenti il Giorno 1 del Ciclo 1.
9) Compromissione della funzionalità cardiaca o cardiopatia clinicamente rilevante, come ad esempio:
• cardiopatia di classe III o IV secondo la classificazione NYHA (New York Heart Association), tra cui aritmia ventricolare, insufficienza cardiaca congestizia o cardiomiopatia clinicamente rilevante preesistente;
• angina pectoris instabile =6 mesi prima dell’inizio dell’assunzione del trattamento dello studio;
• infarto miocardico acuto =6 mesi prima dell’inizio dell’assunzione del trattamento dello studio; oppure
• altra cardiopatia clinicamente rilevante, ad es. ipertensione di grado =3, ipertensione labile all’anamnesi o storia di scarsa aderenza al regime antipertensivo.
10) Pazienti con neuropatia periferica di Grado =2 .
11) Pazienti con infezione attiva da epatite A, B o C.
12) Malattie intercorrenti non controllate, comprendenti, a titolo esemplificativo ma non esaustivo, infezione in corso o attiva, patologia psichiatrica che limiterebbe l’aderenza ai requisiti dello studio, malattia autoimmune attiva che necessiti di terapia immunosoppressiva, grave immunodeficienza.
13) Diagnosi nota di infezione da virus dell’immunodeficienza umana (HIV).
14) Pazienti con neoplasia maligna primitiva concomitante che richieda un trattamento o che possa rappresentare un fattore di confondimento per l’interpretazione della risposta della malattia in studio.
15) Donne in età fertile in gravidanza o in allattamento.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Treatment-emergent adverse events (TEAES), clinically-significant changes in clinical laboratory test results, ECG and vital sign measurements
- Number of patients with clinical responses as assessed by the Lugano
Classification of response assessments. |
• Eventi avversi emersi durante il trattamento (Treatment Emergent Adverse Event, TEAE), variazioni clinicamente rilevanti dei risultati ai test di laboratorio, dei tracciati ECG e delle rilevazioni dei segni vitali
• Numero di pazienti con risposta clinica (ORR), determinata secondo la Classificazione di Lugano della risposta
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
-AEs will be monitored continuously throughout the study from the time of the first dose of study treatment until 30 days after the patient's last
study treatment or until the event has resolved or stabilized or an outcome has been reached, whichever comes first. Clinical laboratory tests will be performed at each study visit. ECG assessments will be performed at each IMP dosing visit, at D2 visits in each study part; at screening visit, at EOT visit and possibly at 30-day FU visit.
Vital signs will be assessed at each study visit, except for the D2 and D3 visits in each study part (i.e. C1D2/C1D3 and C3D2/C3D3 in study part 1
(Q3W) and C1D2/C1D3 and C2D2/C2D3 in study part 2 (Q3W and QW)).
- Performed approximately every 6 weeks, beginning at C1D1. |
| -Gli Eventi Avversi saranno monitorati continuamente durante lo studio dalla prima dose di trattamento di studio fino a 30 giorni dopo l'ultimo trattamento del paziente o fino a quando l'evento si è risolto o stabilizzato o è stato raggiunto un risultato, a seconda di quale viene prima. Le prove cliniche del laboratorio saranno effettuate ad ogni visita dello studio. Le valutazioni dell'ECG saranno effettuate ad ogni visita di dosaggio IMP, alle visite D2 in ogni parte dello studio; alla visita di screening, alla visita EOT e possibilmente alla visita di FU a 30 giorni. I segni vitali saranno valutati ad ogni visita di studio, ad eccezione delle visite D2 e D3 di ogni parte di studio (i.e. C1D2/C1D3 e C3D2/C3D3 parte 1 (Q3W) dello studio e C1D2/C1D3 e C2D2/C2D3 nella parte 2 (Q3W e QW)). |
|
| E.5.2 | Secondary end point(s) |
• Parametri PK (valutati come ritenuto più appropriato e comprendenti, a titolo esemplificativo ma non esaustivo): Cmax, AUC0-t, AUCinf, tempo di emivita (t½), CL, Vss, Tmax, sia per Debio 1562 sia per rituximab
• Calcolo di alcuni parametri di tipo “tempo all’evento”:
• PFS e OS
• Tempo alla risposta e durata della risposta
• Immunogenicità di Debio 1562: presenza di ADA umani
|
- PK parameters (evaluated as deemed appropriate but not limited to):
Cmax, AUC0-t,AUCinf terminal half-life (t½), clearance (CL), volume of distribution at steady state (Vss), Tmax, for both Debio 1562 and rituximab
- Calculation of time to event parameters
- Progression-free survival (PFS) and Overall survival (OS)
- Time to response and duration of response (DOR)
- Immunogenicity of Debio 1562: presence of human anti-drug antibody
(ADA) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Calculation of time to event parameters will be assessed as follows:
- PFS: Every 12 weeks (± 4 weeks) from time of last on-study tumor assessment until PD, or starting a subsequent anti-cancer therapy.
- OS: Every 12 weeks (± 4 weeks) from time of 30-day FU visit, for up to 1 year from last patient's first dose (C1D1)
- Time to response and DOR will be estimated for all evaluable patients who achieve an objective response (PR or CR)
- ADA assessment performed at D1 of each cycle, EOT visit and 30-day FU visit |
-I parametri PK saranno valutati ad ogni visita dello studio
-Il calcolo di parametri del tempo dell’ evento sarà valutato come segue:
-PFS: ogni 12 settimane (± 4 settimane) dal momento dell'ultima valutazione del tumore fino al PD, dall’inizio di una successiva terapia anti-cancro.
-OS: ogni 12 settimane (± 4 settimane) dalla visita di FU a 30 giorni , per un massimo di 1 anno dalla prima dose dell'ultimo paziente (C1D1)
-Tempo di risposta e DOR saranno valutati per tutti i pazienti che raggiungono una risposta oggettiva (PR o CR)
-Valutazione ADA eseguita alla D1 di ogni ciclo, visita EOT e 30 giorni
|
|
| 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 | Yes |
| 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) | No |
| 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 | No |
| 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.8.2.4 | 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 |
| Ukraine |
| United States |
| Belgium |
| Bulgaria |
| Hungary |
| Italy |
| Poland |
| Czechia |
|
| 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
|
| The End of Study will be defined as the latter of the completion of the Safety follow-up visit for the last patient remaining on treatment or one year from the last accrued patient’s first visit |
| La fine dello studio sarà definita come l'ultima visita a completamento del follow-up di sicurezza per l'ultimo paziente rimasto sul trattamento o un anno dalla prima visita dell’ultimo paziente. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
