E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
mRNA FGF receptor 1 and 3 positive locally advanced or metastatic urothelial carcinoma progressed after prior platinum-containing chemotherapy |
Positivo mRNA FGF recettori 1 e 3 localmente avanzato o metastatico, con carcinoma uroteliale in progressione sottoposti in precedenza a chemioterapia contenente platino |
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced or metastatic bladder cancer with a high amount of specific cell growth factor receptors 1 and 3 (FGFR1 and 3) in the tumor cells |
Localmente avanzato o metastatico carcinoma uroteliale con quantità elevate di recettore cellulare del fattore di crescita recettore 1 e 3 (FGFR 1 e 3) nelle cellule tumorali |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Primary objective of this trial is to demonstrate the superiority of rogaratinib over chemotherapy in terms of prolonging overall survival of urothelial carcinoma patients with FGFR positive tumors. The objective for the Phase 2 part of the study is to demonstrate the efficacy of rogaratinib over chemotherapy in terms of objective response rate of urothelial carcinoma patients with FGFR positive tumors. |
Obiettivo primario: Dimostrare la superiorità di rogaratinib rispetto alla chemioterapia in termini di prolungamento della sopravvivenza globale dei pazienti affetti da carcinoma uroteliale con tumori positivi per FGFR. L’obiettivo della Fase 2 dello studio è dimostrare l’efficacia di rogaratinib rispetto alla chemioterapia in termini di tasso di risposta obiettiva dei pazienti affetti da carcinoma uroteliale con tumori positivi per FGFR.
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E.2.2 | Secondary objectives of the trial |
Secondary objective of this trial is to evaluate additional efficacy including the following variables: Progression-free survival (PFS) Objective response rate (ORR) Disease control rate (DCR) Duration of response (DOR) and to evaluate the safety of rogaratinib (adverse events) Tertiary objectives are: Patient-reported outcome (PRO) Evaluate biomarkers to investigate the drug (i.e. mode-of-action related) Pharmacokinetics effect and/or safety) and/or the pathomechanism of the disease. Pharmacokinetics |
Obiettivi secondari: • Valutare l’efficacia aggiuntiva, comprensiva delle seguenti variabili: o sopravvivenza libera da progressione (PFS) o tasso di risposta obiettiva (ORR) o tasso di controllo della malattia (DCR) o durata della risposta (DOR) • Valutare la sicurezza di rogaratinib (eventi avversi) Obiettivi terziari: • Esiti riferiti dai pazienti (PRO) • Valutazione dei biomarcatori per analizzare il farmaco (effetto e/o sicurezza correlati al meccanismo d’azione) e/o il meccanismo patologico della malattia • Profilo farmacocinetico |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Existence of archival or fresh biopsy for FGFR testing. FGFR testing of patients will be performed at the investigators' discretion up to a max. of 90 days prior to start of screening (signing of informed consent for study treatment eligibility). Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment within this timeframe. If the patient is positive for FGFR 1 and/or 3 and is unable start screening by 90 days after FGFR testing, the patient may still be considered for screening after discussion with the sponsor's designated medical representative and approval by the sponsor Male or female patients ≥ 18 years of age (at least age of legal maturity). Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria: Histologically or cytologically confirmed. Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced (T4b, any N; or any T, N 2−3) or metastatic disease (any T, any N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3). ECOG Performance Status of 0 or 1. Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12 months of treatment. High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy specimen. At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI. Adequate laboratory and organ function: Absolute neutrophil count (ANC) ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9.0 g/dL (without transfusion or erythropoietin within 4 weeks before randomization). Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Known Gilbert syndrome is allowed if total bilirubin is ≤ 3 x ULN. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer). Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver and bone involvement of their cancer). Lipase < 2 x ULN Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to Modification of Diet in Renal Disease (MDRD) abbreviated formula. International normalized ratio (INR) ≤ 1.5 ULN, and partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 ULN. Patients being treated with anticoagulant, e.g. warfarin or heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR is stable based on a predose measurement as defined by the local standard of care. Women of childbearing potential (WOCBP) and fertile men must agree to use adequate contraception when sexually active from signing of the ICF for study treatment eligibility until at least 12 weeks after the last study drug administration. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control. Highly effective (failure rate of less than 1% per year) contraception methods include: Combined (estrogen and progesterone containing: oral, intravaginal, transdermal) and progesterone-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). Bilateral tubal occlusion or vasectomized partner (provided that partner is the sole sexual partner and has received medical assessment of the surgical success). Sexual abstinence (reliability to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Male patients with a female partner of childbearing potential must use a condom and ensure that an additional form of contraception is also used during treatment and until 12 weeks after last study drug administration. Negative serum pregnancy test in women of childbearing potential (performed within 7 days before randomization). Negative results must be available prior to study drug administration. |
• Disponibilità di un campione bioptico da archivio o appena prelevato per l’analisi dell’FGFR • L’analisi dell’FGFR sarà eseguita sui pazienti a discrezione degli sperimentatori al massimo 90 giorni prima dell’inizio dello screening. In questo periodo di tempo gli sperimentatori dovranno accertarsi che tutti i pazienti siano idonei in termini di stato della malattia e linee di trattamento. • Pazienti di sesso maschile o femminile di età ≥ 18 anni • Carcinoma uroteliale documentato (carcinoma a cellule transizionali), inclusi tumori alla vescica urinaria, pelvi renale, ureteri e uretra, che soddisfi tutti i seguenti criteri o Confermato istologicamente o citologicamente I pazienti con istologie miste devono presentare un pattern a cellule transizionali dominante. o Patologia localmente avanzata (T4b, qualsiasi N; o qualsiasi T, N 2−3) o metastatica (qualsiasi T, qualsiasi N e M1). Il cancro della vescica localmente avanzato deve essere non resecabile, ossia aver invaso la parete pelvica o addominale (stadio T4b) o presentare un interessamento linfonodale bulky (N2-3). • Performance status secondo ECOG pari a 0 o 1 • Progressione della patologia durante o in seguito al trattamento con almeno un regime contenente platino (i pazienti devono essere stati trattati per almeno 2 cicli). Nei pazienti precedentemente trattati con chemioterapia adiuvante/neoadiuvante contenente platino, la progressione deve essersi verificata entro 12 mesi di trattamento. • Livelli elevati di espressione mRNA di FGFR1 o 3 (punteggio RNAscope di 3+ o 4+; la misurazione fa parte di questo protocollo) in un campione tumorale bioptico da archivio o appena prelevato • Almeno 1 lesione misurabile in base ai criteri Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) evidenziata ad una TC o una RM con mezzo di contrasto (se non controindicata) Per l’elenco completo dei criteri di inclusione e di esclusione, consultare i paragrafi 6.1 e 6.2 del presente protocollo. |
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E.4 | Principal exclusion criteria |
Previous or concurrent cancer except: cervical carcinoma in situ treated basal-cell or squamous cell skin carcinoma any cancer curatively treated > 3 years before randomization ocuratively treated incidental prostate cancer (T1/T2a) Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has no radiological evidence of tumor growth and is clinically stable with respect to the tumor at randomization. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies). Known human immunodeficiency virus (HIV) infection. Renal dialysis. Any malabsorption condition. Breast-feeding. Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) or with taxanes or vinflunine. More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma. Ongoing or previous anti-cancer treatment within 4 weeks before randomization: Patients who have received prior treatment with anti-CTLA-4 may be enrolled provided at least 5 half-lives (approximately 75 days) have elapsed before randomization. Prior cancer vaccines and cellular immunotherapy are permitted. Previous radiotherapy is acceptable under the following conditions: Therapeutic radiotherapy ≥ 3 weeks before the baseline tumor scan. Palliative radiotherapy for bone metastases or soft tissue lesions is allowed and should be completed >7 days prior to baseline tumor scan. Lesions at the site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease. Anti-cancer therapy is defined as any agent or combination of agents with clinically proven anti-tumor activity administered by any route with the purpose of affecting the malignancy, either directly or indirectly, including palliative and therapeutic endpoints. Use of strong inhibitors and inducers of CYP3A4 (see Appendix 16.1) should have been stopped 2 weeks before randomization. Concomitant therapies that are known to increase serum calcium or phosphate levels and cannot be discontinued or switched to a different medication before randomization. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. Major surgery, or significant trauma within 4 weeks before randomization (central line surgery is not considered major surgery). Unresolved toxicity higher than National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any prior therapy/procedure excluding alopecia, anemia and/or hypothyroidism. History or current condition of an uncontrolled cardiovascular disease including any of the following conditions: Congestive heart failure (CHF) NYHA > Class 2. Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months before randomization). Myocardial infarction (MI) within past 6 months before randomization. Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or digoxin are eligible. Arterial or venous thrombotic events or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before randomization. Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia). Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion. Active infection with hepatitis B or C, requiring treatment Active infections (≥ CTCAE v.4.03 Grade 3) Evidence or history of bleeding diathesis or coagulopathy Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks before randomization. Seizure disorder requiring therapy Serious, non-healing wound, ulcer or bone fracture Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study. Inability to swallow oral medications. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. Previous assignment to study treatment during this study. Investigational drug treatment outside of this study during or within 4 weeks before randomization. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site). |
• Tumore pregresso o concomitante, ad eccezione di o carcinoma cervicale in situ o carcinoma cutaneo basocellulare o squamocellulare trattato o qualsiasi tumore trattato con finalità terapeutiche > 3 anni prima della randomizzazione o carcinoma prostatico incidentale trattato con finalità terapeutiche (T1/T2a) • Trattamento antitumorale in corso o pregresso nelle 4 settimane precedenti la randomizzazione. • Più di due linee precedenti di terapia antitumorale sistemica per il carcinoma uroteliale • Trattamento in corso o pregresso con terapie mirate anti-FGFR (ad esempio inibitori dei recettori tirosin-chinasi, incluso rogaratinib, o anticorpi specifici per FGFR) oppure con taxani o vinflunina • Tossicità non risolta superiore al grado 1 secondo i criteri Common Terminology Criteria for Adverse Events del National Cancer Institute, versione 4.03 (CTCAE v.4.03), imputata a una terapia/procedura precedente, ad esclusione di alopecia, anemia e/o ipotiroidismo • Anamnesi o attuale presenza di malattie cardiovascolari non controllate, incluse le seguenti condizioni: o Insufficienza cardiaca congestizia (ICC) Classe NYHA > 2 o Angina instabile (sintomi di angina a riposo) o angina di nuova insorgenza (nei 3 mesi precedenti la randomizzazione) o Infarto del miocardio (MI) nei 6 mesi precedenti la randomizzazione o Aritmie cardiache instabili che richiedono una terapia antiaritmica. I pazienti affetti da aritmia controllata con una terapia antiaritmica, ad esempio con betabloccanti o digossina, sono eleggibili. • Eventi trombotici o embolici arteriosi o venosi, quali accidente cerebrovascolare (inclusi attacchi ischemici transitori), trombosi venosa profonda o embolia polmonare nei 3 mesi precedenti la randomizzazione • Attuale evidenza di un’alterazione endocrina dell’omeostasi del calcio e del fosfato (ad esempio disturbo delle paratiroidi, anamnesi di paratiroidectomia, lisi tumorale, calcinosi tumorale, ipercalcemia paraneoplastica) • Qualsiasi emorragia/sanguinamento di Grado CTCAE v.4.03 ≥ 3 nelle 4 settimane precedenti alla randomizzazione • Attuale diagnosi di distacco della retina, distacco dell’epitelio pigmentato retinico (RPED), retinopatia sierosa o occlusione venosa retinica Per l’elenco completo dei criteri di inclusione e di esclusione, consultare i paragrafi 6.1 e 6.2 del presente protocollo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival is the primary efficacy variable. The primary efficacy variable is overall survival (OS). OS data will be considered mature and the final OS analysis (i.e. primary completion) will be performed when approximately a total of 232 PIK3CA and RAS WT patients have died, in accordance with the power calculations specified for the full analysis set (FAS). For the primary efficacy variable of overall survival, a hierarchical fixed-sequence procedure based on stratified log-rank test controlling type I error at a level of 0.025 (onesided) will be conducted for the WT population first (step 1). A full alpha of 0.025 (one-sided) will be passed on to OS in all study population and some selected secondary endpoints (step 2), if and only if the null hypothesis of OS for WT population is rejected.in the following sequence: step 1) WT population; step 2) all study population. Step 2 will be tested if and only if the null hypothesis of step 1) is rejected. Details on controlling family-wise type I error within step 2 for OS in all study population and selected secondary endpoints will be specified in the Statistical Analysis Plan (SAP). In addition, the hazard ratio (rogaratinib / chemotherapy) for OS and its 95% confidence interval will be calculated using the Cox model, stratified by the same factors used for randomization, for both PIK3CA and/or RAS WT and all study population (referred as "both populations" below). Kaplan-Meier (KM) estimates for OS and KM survival curves will also be presented for each treatment arm and both populations. The KM estimates at time points such as 3 months, 6 months etc. together with corresponding 95% confidence intervals as well as the differences of these estimates will also be calculated between the rogaratinib arm and the chemotherapy arm for both populations. This study follows a Phase 2/3 design with interim analysis, meaning the patients recruited to the Phase 2 part of the study will automatically continue to the Phase 3 part without interruption if futility is not demonstrated at the 1st interim ORR analysis. The Phase 2 part will end at the time of the cut-off for the 1st interim ORR analysis. To help structure the protocol flow, we present this Phase 2/3 study as one study protocol with two interim analyses, while the first interim indicates the end of the Phase 2 part, and the second and final analyses are considered as the Phase 3 part including Phase 2 patients in the analyses. |
La variabile primaria di efficacia è la sopravvivenza globale (OS). I dati relativi all’OS saranno considerati maturi e l’analisi finale riguardante l’OS (analisi primaria di completamento) sarà eseguita dopo il decesso di un totale approssimativo di 232 pazienti con PIK3CA e RAS WT, in conformità ai calcoli di potenza specificati per il full analysis set (FAS). Per la variabile primaria di efficacia di sopravvivenza globale, sarà condotto prima un test log rank stratificato con controllo dell’errore di tipo I a un livello di 0,025 (a una coda) per la popolazione WT (step 1). Un alfa completo di 0,025 (a una coda) sarà applicato all’OS in tutte le popolazioni dello studio e ad alcuni endpoint secondari selezionati (step 2) se, e soltanto se, l’ipotesi nulla dell’OS per la popolazione WT sarà rigettata. Informazioni dettagliate sul controllo dell’errore di tipo I family-wise nell’ambito dello step 2 per l’OS nell’intera popolazione dello studio ed endpoint secondari selezionati saranno specificate nel Piano di analisi statistica (SAP). Inoltre, l’hazard ratio (rogaratinib/chemioterapia) per l’OS e il relativo intervallo di confidenza al 95% saranno calcolati utilizzando il modello di Cox, stratificato in base ai medesimi fattori utilizzati per la randomizzazione, sia per la popolazione con PIK3CA e RAS WT sia per l’intera popolazione dello studio (denominate “entrambe le popolazioni” nel prosieguo). Anche le stime di Kaplan-Meier (KM) per l’OS e le curve di sopravvivenza di KM saranno presentate per ciascun braccio di trattamento e per entrambe le popolazioni. Anche le stime di KM in corrispondenza di intervalli temporali quali 3 mesi, 6 mesi, ecc., insieme ai corrispondenti intervalli di confidenza al 95%, e le differenze di tali stime saranno calcolati tra il braccio rogaratinib e il braccio chemioterapia per entrambe le popolazioni. Questo studio segue un disegno di fase 2/3 con analisi ad interim. Ciò significa che se in occasione della 1a analisi ORR intermedia non ne sarà dimostrata la inutilità, i pazienti reclutati per la fase 2 dello studio proseguiranno automaticamente con la fase 3, senza alcuna interruzione. La fase 2 terminerà in corrispondenza del cut-off per la 1a analisi ORR ad interim. Per agevolare la strutturazione dello schema del protocollo, presentiamo questo studio di fase 2/3 come un solo protocollo dello studio con due analisi ad interim, in cui la prima analisi ad interim segna la fine della fase 2, mentre la seconda analisi ad interim e l’analisi finale costituiscono la fase 3 e includono i pazienti della fase 2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Final OS analysis: at approx. 232 deaths in WT population (approx. 44.9 months after the start of randomization). In addition, two interim analyses are planned: 1st interim ORR analysis (Phase 2 part): At approx. the first 116 PIK3CA and RAS WT patients complete 4.5 months of Treatment. 2nd interim OS analysis (Phase 3 part): At approx. 116 deaths in PIK3CA and RAS WT patients (50% of 232 total death events in WT population, approx. 28.7 months after start of randomization). |
Analisi finale dell’OS: al raggiungimento di circa 232 decessi nella popolazione WT (circa 44,9 mesi dopo l’inizio della randomizzazione). Sono, inoltre, previste due analisi intermedie: • 1a analisi ORR ad interim (fase 2): all’incirca quando i primi 116 pazienti con PIK3CA e RAS WT avranno completato 4,5 mesi di trattamento 2a analisi OS ad interim (fase 3): all’incirca dopo 116 decessi tra i pazienti con PIK3CA e RAS WT (50% dei 232 eventi di decesso totali nella popolazione WT, circa 28,7 mesi dopo l’inizio della randomizzazione)
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E.5.2 | Secondary end point(s) |
Vedere Allegato I Appendice 5 (26.01.2018) |
Vedere Allegato I Appendice 5 (26.01.2018) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy variables will be analyzed based on final database when approximately a total of 232 PIK3CA and RAS WT patients have died (approx. 44.9 months after the start of randomization). |
Le variabili di efficacia secondaria saranno analizzate nel database finale dopo il decesso di un totale approssimativo di 232 PIK3CA e RAS wt (appross. 44.9 mesi dopo l'inizio della randomizzazione) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 107 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Canada |
China |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hong Kong |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Russian Federation |
Singapore |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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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For each participating EU country, the end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last patient for all centers in the respective country has occurred. The end of the study as a whole will be reached when the last visit of the last patient has been achieved in all participating centers (EU and non-EU), or the primary completion event has been reached, whichever comes later. |
LVLS |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 29 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 11 |