| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced progressive pNETs |
| fremskredne progredierende pNET |
|
| E.1.1.1 | Medical condition in easily understood language |
| advanced progressive pNETs |
| fremskredne progredierende pNET |
|
| 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 | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067517 |
| E.1.2 | Term | Pancreatic neuroendocrine tumour |
| 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 | 10068909 |
| E.1.2 | Term | Pancreatic neuroendocrine tumour metastatic |
| 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 |
To compare the efficacy of the combination STZ-5FU chemotherapy
followed by Everolimus 10 mg/day upon progression versus the reverse
sequence in the treatment of advanced pancreatic neuroendocrine
tumours (pNET), in terms of rate of patients with second progression
free survival at 140 +/- 8 weeks of treatment, assessed by local investigator
using RECIST criteria 1.0. |
| At sammenligne effekten af kombinationen STZ-5FU-kemoterapi efterfulgt af everolimus 10 mg/dag efter progression versus den omvendte rækkefølge til behandling af fremskredne pankreatiske neuroendokrine tumorer (pNET) med hensyn til procentdelen af patienter med endnu en progressionsfri overlevelse efter 140 +/- 8 ugers behandling, vurderet i henhold til RECIST-kriterierne 1.0. |
|
| E.2.2 | Secondary objectives of the trial |
•To describe the efficacy of the two sequences of treatment STZ-5FU and
everolimus 10 mg/day, as a continuous variable Hazard Ratio (HR), in
advanced pNETs.
• To determine whether the overall survival of patients with advanced
pNETs could be modified by the upfront administration of each other
treatment, STZ-5FU and everolimus 10 mg/day, upon progression.
• To compare the clinical activity of STZ-5FU and everolimus 10 mg/day
treatment given in 1st or 2nd place in advanced pNETS, in terms of time
to first and second progression, response rate (RR), and early
biochemical response (4 week CgA levels), Quality of Life and cost-effectiveness of each sequence, and to investigate the criteria for measuring progression free survival (RECIST 1.0, RECIST 1.1, composite RECIST 1.0
and composite RECIST 1.1) that correlates better with overall survival.
• To compare the safety and tolerability of the two tratment sequences
• To compare the cost-effectiveness of the two tratment sequence |
•beskrive effekten af de 2 behandlingsrækkefølger med STZ-5FU og everolimus 10 mg/dag som et kontinuerligt variabelt risikoforhold (HR) ved fremskredne pNET
•bestemme om den samlede overlevelse hos patienter med fremskredne pNET kan modificeres vha. up-front administration af henholdsvis den ene og den anden behandling
•sammenligne den kliniske aktivitet forbundet med behandling med STZ-5FU og everolimus 10 mg/dag givet i 1. eller 2. position ved fremskredne pNET med hensyn til tid til første og anden progression, responsrate (RR) og tidligt biokemisk respons (CgA-niveauer efter 4 uger), livskvalitet og kost effektivitet for hver rækkefølge samt at undersøge, hvilke målingskriterier for progressionsfri overlevelse (RECIST 1.0, RECIST 1.1, kombineret RECIST 1.0 og kombineret RECIST 1.1), der bedst korrelerer med den samlede overlevelse
•sammenligne sikkerheden og tolerabiliteten af de 2 behandlingsrækkefølger
•sammenligne kost effektivitet ved de 2 behandlingsrækkefølger |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1) Detection of predictive markers
Versión 2.0 of date 30th of January 2014
The objective of this sub-study is the detection of predictive markers of
pNET and patients' outcome, on paraffin embedded tumour blocks from
patients included in SEQTOR clinical trial.
2) Evaluation of a blood-based transcriptional assay - the NETest - as a
biomarker of neuroendocrine tumor response
NETest - Detection of a circulating NET fingerprint
3) PanNETassigner molecular subtypes assay
Ver 1.0, 7th August 2018
The aim of this sub-study is to evaluate the predictive value of the
PanNET assigner assay for patients undergoing treatment with
chemotherapy and everolimus. This test uses molecular technologies,
looking at changes in RNA seen in tumor samples, to divide pancreatic
NET patients into different molecular subtypes. It will be evaluated
whether these molecular subtype results in combination with clinical
data from the SEQTOR study can be used for patient prognostication and
classification as well as prediction of treatment response for pNET |
1) Opdage prediktive markører
Version 2.0 2014-01-30
Formålet med sub-studiet er at opdage predikative markører for
progression ved pNET, på paraffinin indstøbte tumorblokke fra patienter i
SEQTOR-studiet.
2) Evaluering af blodprøvebaseret transskriptionsanalyse – ”NETest” – som en biomarkør for neuroendokrin tumorrespons
Version 1.0, 13. marts 2015
Formålet med dette under-studie er at bruge NETest som mål for behandlingsrespons i SEQTOR studiet. NETest vil også kunne give yderligere informationer, der kan bruges til at måle terapeutisk effekt.
3)Ver 1.0, 7. august 2018
Formålet med dette delstudium er at evaluere den forudsigelige værdi af
PanNET assigner assay for patienter, der behandles med
kemoterapi og everolimus. Denne test bruger molekylære teknologier,
ser på ændringer i RNA set i tumorprøver, for at opdele bugspytkirtlen
NET patienter i forskellige molekylære subtyper. Det vil blive evalueret
hvorvidt disse molekylære subtyper resulterer i kombination med klinisk
data fra SEQTOR-undersøgelsen kan anvendes til patientprognosticering og
klassificering samt forudsigelse af behandlingsrespons for pNET
|
|
| E.3 | Principal inclusion criteria |
• Adult patients ≥ 18 years old.
• Histologically proven diagnosis of unresectable or metastatic,
advanced pancreatic NET.
• Documented confirmation of pancreatic NET G1 or G2 as per ENETS
classification system:
• G1: <2 mitoses per 2 mm2 and/or Ki-67 index ≤ 2%
• G2: 2–20 mitoses per 2 mm2 and/or Ki-67 index >2% and ≤ 20%
• Patients from whom a paraffin-embedded primary tumour or
metastasis block is available and sent by courier (Section 7.2.10).
Patient should give his/her consent for its use in future investigations.
• Before study inclusion, patients must show progressive disease
documented by radiology within 12 months prior to study inclusion. If
patient received anti-tumour therapy during the past 12 months, he/she
must have radiological documentation of progressive disease while on or
after receiving that anti-tumour therapy. Treatment Naive patients can be also
included if, under investigator's judgement, the patient needs active
treatment with either chemotherapy or everolimus.
• Before starting with the second treatment in sequence, patients must
show documented disease progression by RECIST 1.0 (local assessment)
while on anti-tumour therapy or in case of toxicity caused by the first treatment period.
• ECOG Performance status score 0 - 2.
• Life expectancy > 12 months.
• Presence of measurable disease as per RECIST criteria 1.0,
documented by a Triphasic Computed Tomography (CT) scan or
multiphase MRI radiological assessment.
• Previous treatment with somatostatin (SS) analogues is allowed. Only
those patients with active functioning syndrome at entry can continue
with SS analogues during the study.
• Adequate bone marrow function, documented by ANC > 1.5 x 109/L,
platelets > 100 x 109/L, haemoglobin > 9 g/dL.
• Adequate liver function documented by: serum bilirubin ≤ 2.0 mg/dL,
INR ≤ 2, ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver
metastasis).
• Adequate renal function documented by: serum creatinine < 1.5 x ULN.
• Fasting serum cholesterol < 300 mg/dL or < 7.75 mmol/L and fasting
triglycerides < 2.5 x ULN. If one or both thresholds are exceeded, the
patient may only be included after starting treatment with an adequate
lipid-lowering agent.
• Women with child-bearing potential must have a negative serum
pregnancy test within 14 days prior to enrolment and/or a urine
pregnancy test 48 hours before the administration of the first study
treatment.
• Written Informed Consent obtained according to local regulations. |
• Voksne patienter ≥ 18 år.
• Histologisk påvist diagnose af uresekterbar eller metastatisk, fremskreden pankreatisk NET.
• Dokumenteret bekræftelse af pankreatisk NET G1 eller G2 i henhold til ENET-klassifikationssystemet:
• G1: <2 mitoser pr. 2 mm2 og/eller Ki-67 indeks ≤ 2 %
• G2: 2–20 mitoser pr. 2 mm2 og/eller Ki-67 indeks >2 % og ≤ 20 %
• Patienter for hvilke der foreligger en paraffinindstøbt primærtumor eller en blok med metastasevæv, som er fremsendt med kurér (afsnit 7.2.10). Patienten skal give sit samtykke til, at denne anvendes i fremtidige undersøgelser.
• Før inklusion i forsøget skal patienterne udvise progressiv sygdom dokumenteret vha. røntgen inden for 12 måneder før inklusion. Hvis patienten har modtaget antitumorbehandling i løbet af de sidste 12 måneder, skal han/hun have radiologisk dokumentation for progressiv sygdom under eller efter modtagelse af den pågældende antitumorbehandling. Behandlingsnaive patienter kan også blive inkluderet, hvis investigatoren vurderer, at patienten har brug for aktiv behandling med enten kemoterapi eller everolimus.
• Før starten af den anden behandling i rækkefølgen skal patienterne udvise dokumenteret sygdomsprogression ifølge RECIST 1.0 (lokal vurdering) under modtagelse af antitumorbehandling eller i tilfælde af toksicitet forårsaget af den første behandlingsperiode.
• ECOG Performance status score på 0 - 2.
• Forventet levetid > 12 måneder.
• Forekomst af målbar sygdom i henhold til RECIST-kriterierne 1.0, dokumenteret vha. en trefaset computertomografi- (CT-) scanning eller en flerfaset MR-scanning.
• Tidligere behandling med somatostatin- (SS-) analoger er tilladt. Kun patienter med aktivt fungerende syndrom ved indtræden kan fortsætte med SS-analoger under forsøget.
• Adækvat knoglemarvsfunktion, dokumenteret ved ANC > 1,5 x 109/l, trombocytter > 100 x 109/l, hæmoglobin > 9 g/dl.
• Adækvat leverfunktion dokumenteret ved: serum bilirubin ≤ 2,0 mg/dl, INR ≤ 2, ALT og AST ≤ 2,5 x ULN (≤ 5 x ULN hos patienter med levermetastase).
• Adækvat nyrefunktion dokumenteret ved: serum-kreatinin < 1,5 x ULN.
• Fastende kolesterol i serum < 300 mg/dl eller < 7,75 mmol/l og fastende triglycerider < 2,5 x ULN. Hvis den ene eller begge tærskler overskrides, må patienten kun blive inkluderet efter start af behandling med et passende lipidsænkende middel.
• Fødedygtige kvinder skal have en negativ serumgraviditetstest inden for 14 dage før tilmelding og/eller en uringraviditetstest 48 timer før administration af den første forsøgsbehandling.
• Skriftligt informeret samtykke indhentet i henhold til lokale regler.
|
|
| E.4 | Principal exclusion criteria |
• Patients with poorly differentiated pancreatic neuroendocrine tumor;
this is, pNET G3 as per ENETS classification system:
• G3: 21 or more mitoses per 2 mm2 and/or Ki-67 index >20%
• Previous treatment with chemotherapy and/or mTOR inhibitors
(sirolimus, temsirolimus, everolimus, deforolimus) or tirosyne kinase
inhibitors (sunitinib, sorafenib, axitinib, pazopanib, regerafenib).
• Immune therapy or radiation therapy within 4 weeks prior to the
patient entering the study.
• Hepatic artery embolization within the last 6 months (1 month if there
are other sites of measurable disease), or cryoablation/radiofrequency
ablation of hepatic metastasis within 2 months of enrolment.
• Previous treatment with Peptide-Receptor Radionuclide Therapy
(PRRT) within the last 6 months and/or without progression following
PRRT.
• Uncontrolled diabetes mellitus defined as: fasting serum glucose > 1.5
x ULN.
• Patients with any severe and/or uncontrolled medical conditions such
as:
• unstable angina pectoris, symptomatic congestive heart failure,
myocardial infarction ≤ 6 months prior to randomization, serious
uncontrolled cardiac arrhythmia,
• active or uncontrolled severe infection,
• severe hepatic impairment (Child Pugh C) is not allowed; moderate
hepatic impairment (Child Pugh B and A) requires a reduced dose of
everolimus (5mg and 7.5 mg daily respectively). Positive HBV-DNA and
or HBsAg patients at screening should receive prophylaxis treatment.
• severely impaired lung function (spirometry and DLCO 50% or less of
normal and O2 saturation 88% or less at rest on room air),
• active, bleeding diathesis
• Treatment with potent inhibitors or inducers of CYP3A isoenzyme
(rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole,
voriconazole, ritonavir, telithromycin) within 5 days immediately before
the start of treatment (a list of clinically significant drug interactions is
shown in section 6. Concomitant Medication).
• Patients on chronic treatment with corticosteroids or any other
immunosuppressive agent.
• Patients known to be HIV seropositive.
• Known intolerance or hypersensitivity to everolimus or its excipients
or other rapamycin analogues. Patients with rare hereditary problems of
galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicinal product.
• Known intolerance or hypersensitivity to 5FU or STZ or its excipients.
• Participation in any other clinical trial or concomitant treatment with
any other investigational drug.
• No other prior or concurrent malignancy is allowed except for the
following: adequately treated basal cell or squamous cell skin cancer, or
other adequately treated in situ cancer, or any other cancer from which
the patient has been disease free for ≥ 3 years.
• Pregnant, lactating women or fertile adults not using effective birth control methods. If barrier contraceptives are used, these must be continued to be used throughout the trial by both sexes and for up to 8
weeks after the end of treatment.
• For administrative matters (insurance) patients ≥ 95 are not allowed during the trial. |
• Patienter med dårligt differentieret pankreatisk neuroendokrin tumor, dvs. pNET G3 i henhold til ENET-klassifikationssystemet:
• G3: 21 eller flere mitoser pr. 2 mm2 og/eller Ki-67 indeks >20 %
• Tidligere behandling med kemoterapi og/eller mTOR-hæmmere (sirolimus, temsirolimus, everolimus, deforolimus) eller tirosinkinasehæmmere (sunitinib, sorafenib, axitinib, pazopanib, regerafenib).
• Immunterapi eller stråleterapi inden for 4 uger før patientens indtræden i forsøget.
•ď€ Leverarterieemboli inden for de seneste 6 måneder (1 måned hvis der findes andre steder med målbar sygdom) eller kryoablation/radiofrekvensablation af levermetastase inden for 2 måneder før optagelse.
• Tidligere behandling med peptidreceptor-radionuklidterapi (PRRT) inden for de sidste 6 måneder og/eller uden progression efter PRRT.
• Ukontrolleret diabetes mellitus defineret som: fastende serum glucose > 1,5 x ULN.
• Patienter med alvorlige og/eller ukontrollerede medicinske tilstande, fx:
• ustabil angina pectoris, symptomatisk hjerteinsufficiens, myokardieinfarkt ≤ 6 måneder før randomisering, svær ukontrolleret hjertearytmi,
• aktiv eller ukontrolleret alvorlig infektion,
• svært nedsat leverfunktion (Child Pugh C) er ikke tilladt; moderat nedsat leverfunktion (Child Pugh B og A) kræver en reduceret dosis af everolimus (henholdsvis 5 mg og 7,5 mg daglig). Patienter, der er HBV-DNA-positive og/eller HBsAg-positive ved screening skal modtage profylaktisk behandling.
• svært nedsat lungefunktion (spirometri og DLCO 50 % eller lavere af normalværdien og iltmætning 88 % eller lavere ved hvile i rumluft),
• aktiv, blødende diatese
• Behandling med kraftige hæmmere eller inducere af CYP3A-isoenzym (rifabutin, rifampicin, clarithromycin, ketoconazol, itraconazol, voriconazol, ritonavir, telithromycin) inden for 5 dage umiddelbart før start af behandling (der vises en liste over klinisk signifikante lægemiddelinteraktioner i afsnit 6. Samtidig medicinering).
• Patienter, der modtager kronisk behandling med kortikosteroider eller andre immunsupprimerende midler.
• Patienter, der vides at være HIV-seropositive.
• Kendt intolerans eller hypersensitivitet over for everolimus eller dets hjælpestoffer eller andre rapamycinanaloger. Patienter med sjælden arvelig galactose-intolerans, Lapp lactase-insufficiens eller glucose-galactosemalabsorption bør ikke tage dette lægemiddel.
• Kendt intolerans eller hypersensitivitet over for 5FU eller STZ eller dets hjælpestoffer.
• Deltagelse i et andet klinisk forsøg eller samtidig behandling med et andet testpræparat.
• Ingen anden tidligere eller ledsagende malignitet er tilladt, undtagen følgende: adækvat behandlet basalcelle- eller spinocellulær hudcancer, eller anden adækvat behandlet in situ cancer eller anden cancersygdom, hvorfra patienten har været sygdomsfri i ≥ 3 år.
• Gravide kvinder, kvinder der ammer eller fertile voksne, som ikke anvender effektive præventionsmetoder. Ved brug af barriere-præventionsmidler skal disse fortsat bruges af begge køn under hele forsøget og op til 8 uger efter behandlingens afslutning.
• Af administrative årsager (forsikring) er patienter ≥ 95 år ikke tilladt under forsøget.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Rate of second progression free survival is defined as: PFS of Course 1 +
interval between treatments + PFS of Course 2, where PFS1 represents
progression free survival of Course 1 and PFS2 represents progression
free survival of Course 2.
It will be expressed as the rate of second progression free survival: this
is the proportion of patients which are free of second progression at 140
+/- 8 weeks. |
Forekomst af sekundærprogressionsfri overlevelse defineret som: PFS
for kur 1 + interval mellem behandlingerne + PFS for kur 2, hvor PFS1
repræsenterer progressionsfri overlevelse for kur 1 og PFS2
repræsenterer progressionsfri overlevelse for kur 2.
Det vil blive udtrykt som andelen af sekundær progressionsfri overlevelse: dette
er den andel af patienter, der er fri for sekundær progression ved 140
+/- 8 uger.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1 HR of second progression free survival (PFS of Course 1 + interval
between treatments + PFS of course 2).
2 Time to first progression of STZ-5FU and Everolimus 10 mg/day or the
reverse sequence in advanced pNETs.
3 Time to second progression of STZ-5FU and Everolimus 10 mg/day or
the reverse sequence in advanced pNETs.
4 Time from first progression to second progression of STZ-5FU and
Everolimus 10 mg/day or the reverse sequence in advanced pNETs.
5 Response rate of STZ-5FU and Everolimus 10 mg/day or the reverse
sequence in advanced pNETs assessed every 12 weeks.
6 Quality of life score at baseline, upon progression and 30 days after
the last dose of study treatment (both sequences).
7 CgA levels at baseline and at 4 weeks of treatment start.
8 Correlation between the four criteria for second progression free
survival (RECIST 1.0, RECIST 1.1, composite RECIST 1.0 and composite
RECIST 1.1) and Kendall tau variables.
9 Overall survival (OS) of patients on treatment with the combination
STZ-5FU chemotherapy followed by Everolimus 10 mg/day upon
progression or the reverse sequence, in the treatment of advanced
pancreatic neuroendocrine tumours (pNET).
10 Number of adverse events, dose reductions, and total dose
administered on patients treated with STZ-5FU followed by everolimus
10 mg/day or the reverse sequence, in advanced pNETs.
11 Ratio of Incremental cost-effectiveness (ICER) of the differential of costs
incurred on by each treatment arm (A and B): ICER= (Arm A costs – Arm
B costs)/(Arm A 2nd PFS – Arm B 2nd PFS). |
1 HR ved sekundærprogressionsfri overlevelse (PFS for kur 1 + interval
mellem behandlingerne + PFS for kur 2)
2 Tid til første progression med STZ-5FU og Everolimus 10 mg/dag,
eller omvendt rækkefølge, ved framskredne pNET.
3 Tid til anden progression med STZ-5FU og Everolimus 10 mg/dag,
eller omvendt rækkefølge, ved framskredne pNET.
4 Tid til første progression til anden progression med STZ-5FU og
Everolimus 10 mg/dag, eller omvendt rækkefølge, ved framskredne pNET.
5 Responsfrekvens med STZ-5FU og Everolimus 10 mg/dag, eller
omvendt rækkefølge, ved framskredne pNET, målt hver 12. uge.
6 Livskvalitetspoint ved baseline, ved progression og 30 dage efter afgivelse af
sidste dosis af studiebehandlingen (begge sekvenserne)
7 CgA niveauer ved baseline og 4 uger efter behandlingsstart.
8 Korrelation mellem de fire kriterier for sekundærprogressionsfri overlevelse (RECIST 1.0, RECIST 1.1 og RECIST 1.0 tilsammen och RECIST 1.1 tilsammen) samt Kendall tau variabler.
9 Total overlevelse hos patienter som behandles med kombinationen
STZ-5FU kemoterapi efterfulgt af Everolimus 10 mg/dag ved progression, eller
omvendt rækkefølge, ved framskridne pNET
10 Antal uønskede hændelser, dosismindskninger og totaldosis som
administrerets til patienter som behandledes med STZ-5FU efterfulgt af
everolimus 10 mg/dag eller dosering i omvendt rækkefølge, ved framskredne
pNET.
11 Graden af inkrementel kost effektivitet (ICER) i forskellen mellem
omkostninger som tilkom ved hver behandlingsarm (A og B): ICER=
(Arm As omkostninger – Arm Bs omkostninger)/(Arm A 2. PFS – Arm B 2.
PFS).
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At LVLS.
2. At First visit of second treatment.
3. At LVLS.
4. At LVLS.
5. Every 12 weeks.
6. At baseline, upon progression and 30 days after the last dose of
study treatment.
7. At baseline and at 4 weeks of treatment start.
8. At every tumor assessment (every 12 weeks)
9. At LVLS.
10. At every cycle.
11. At LVLS. |
1. ved LVLS.
2. ved det første besøg af anden behandling.
3. ved LVLS.
4. ved LVLS.
5. hver 12. uge
6. ved baseline, ved progression 30 dage efter afgivelse af sidste dosis af
studiebehandlingen
7. ved baseline og 4 uger efter behandlingsstart
8. ved hver tumorbedømmelse (hver 12. uge)
9.ved LVLS.
10. ved hver cyklus
11. ved LVLS.
|
|
| 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 | No |
| 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 | Yes |
| 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 | 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
| LVLS - The study will end when all patients are followed-up to patient death, or 140+/-8 weeks + 30 days safety FU. |
| LVLS - Undersøgelsen afsluttes, når alle patienter følges op til patientdød eller 140 +/- 8 uger + 30 dages sikkerhed FU. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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 |
Print
