Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
1,397
Countries
13
Sites
57
High Risk Non-muscle invasive bladder cancer
1. Cohort A: To compare the CRR for the combination of pembrolizumab + BCG versus BCG alone in participants with CIS 2. Cohort B: To compare the EFS between participants who receive pembrolizumab + BCG (reduced maintenance) versus BCG alone 3. Cohort B: To compare the EFS between participants who receive pembrolizumab+…
Key facts
- Sponsor
- Merck Sharp & Dohme LLC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Nov 2018 → ongoing
- Decision date (initial)
- 2023-05-02
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Merck Sharp & Dohme LLC
External identifiers
- EU CT number
- 2022-501817-29-00
- EudraCT number
- 2018-001967-22
- WHO UTN
- U1111-1282-1555
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Pharmacokinetic, Pharmacogenomic, Others, Therapy
1. Cohort A: To compare the CRR for the combination of pembrolizumab + BCG versus BCG alone in participants with CIS
2. Cohort B: To compare the EFS between participants who receive pembrolizumab + BCG (reduced maintenance) versus BCG alone
3. Cohort B: To compare the EFS between participants who receive pembrolizumab+ BCG (full maintenance) versus BCG alone
Secondary objectives 13
- Cohort A: To compare the EFS between participants who receive pembrolizumab + BCG and BCG alone
- Cohort A: To compare the following endpoints between participants who receive pembrolizumab + BCG and BCG alone: RFS, OS, DSS, Time to cystectomy
- Cohort A: To assess the following endpoints in participants who receive pembrolizumab + BCG and BCG alone: 12-month EFS rate, DOR in CIS participants with a CR, 12-month DOR rate in CIS participants with a CR
- Cohort A: To determine the safety and tolerability of pembrolizumab + BCG
- Cohort A: To evaluate changes from baseline and TDD in HRQoL scores in both treatment groups, using two general instruments (EORTCQLQ-C30, and EuroQoL EQ-5D-5L) and one disease-specific instrument EORTC QLQ-NMIBC24
- Cohort B: To compare the CRR for the combination of pembrolizumab + BCG (reduced maintenance) versus BCG alone in participants with CIS
- Cohort B: To compare the CRR for the combination of pembrolizumab + BCG (full maintenance) versus BCG alone in participants with CIS
- Cohort B: To compare the following endpoints between participants who receive pembrolizumab + BCG (reduced maintenance) and BCG alone: RFS, OS, DSS, Time to cystectomy
- Cohort B: To compare the following endpoints between participants who receive pembrolizumab + BCG (full maintenance) and BCG alone: RFS, OS, DSS, Time to cystectomy
- Cohort B: To compare the following endpoints in participants with CIS who receive pembrolizumab + BCG (reduced maintenance), pembrolizumab + BCG (full maintenance), and BCG alone: DOR, 12-month DOR rate
- Cohort B: To assess the 24-month EFS rate in participants who receive pembrolizumab + BCG (reduced maintenance), pembrolizumab + BCG (full maintenance) and BCG alone
- Cohort B: To evaluate changes from baseline and TTD in HRQoL scores in all treatment groups, using two general instruments (EORTC QLQ-C30, and EuroQoL EQ-5D-5L) and one disease-specific instrument EORTC QLQ-NMIBC24
- Cohort B: To determine the safety and tolerability of pembrolizumab + BCG
Conditions and MedDRA coding
High Risk Non-muscle invasive bladder cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10022877 | Invasive bladder cancer | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Unblinded open-label treatment In adult participants (≥18 years of age) with HR NMIBC that is either a) persistent or recurrent following BCG induction (Cohort A) or b) naïve to BCG treatment (Cohort B)
|
Randomised Controlled | None | Cohort A- BCG Post-induction Cohort: Arms A1 (BCG with pembrolizumab) and A2 (BCG monotherapy) Cohort B- BCG Naïve: Arms B1(Reduced BCG maintenance with pembrolizumab), B2 (Full BCG Maintenance with pembrolizumab, and B3 (BCG Monotherapy) |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
- Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
- Has provided tissue for biomarker analysis
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Has adequate organ function
- During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
- Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last
- BCG Post-induction Cohort (Cohort A) Only: Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
- BCG Post-induction Cohort (Cohort A) Only: Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
Exclusion criteria 18
- Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
- Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
- Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
- Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
- Has an active infection or diagnosis requiring systemic antimicrobial therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has current active tuberculosis
- Has had an allogenic-tissue/solid organ transplant
- Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
- BCG Post-induction Cohort (Cohort A) Only: Has persistent T1 disease following an induction course of BCG
- BCG Naïve Cohort (Cohort B) Only: Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
- Event-Free Survival (EFS) (Cohort B)
Secondary endpoints 18
- EFS (Cohort A)
- Recurrence-Free Survival (RFS) (Cohorts A and B)
- Overall Survival (OS) (Cohorts A and B)
- Disease Specific Survival (DSS) (Cohorts A and B)
- Time to Cystectomy (Cohorts A and B)
- 12-Month EFS Rate (Cohort A)
- Duration of Response (DOR) (Cohorts A and B)
- 12-Month DOR Rate (Cohorts A and B)
- Percentage of Participants Experiencing Adverse Events (AEs) (Cohorts A and B)
- Percentage of Participants Discontinuing Study Drug Due to AEs (Cohorts A and B)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
- Change from Baseline in EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Cohorts A and B)
- Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score (Cohorts A and B)
- Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (Cohorts A and B)
- Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
- TTD in the EQ-5D-5L VAS (Cohorts A and B)
- CRR by BICR (Cohort B)
- 24-Month EFS Rate (Cohort B)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
KEYTRUDA 25 mg/mL concentrate for solution for infusion
PRD4323105 · Product
- Active substance
- Pembrolizumab
- Substance synonyms
- Lambrolizumab, MK-3475, SCH-900475, ABP 234
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 7000 mg milligram(s)
- Max treatment duration
- 105 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FF02 — -
- Marketing authorisation
- EU/1/15/1024/002
- MA holder
- MERCK SHARP & DOHME BV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Bacillus Calmette-Guérin (Bcg), Tice
SUB25779 · Substance
- Active substance
- Bacillus Calmette-Guérin (Bcg), Tice
- Pharmaceutical form
- POWDER FOR INTRAVESICAL SUSPENSION
- Route of administration
- INTRAVESICAL USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 1350 mg milligram(s)
- Max treatment duration
- 147 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
Bacillus Calmette-Guérin (Bcg), Tice
SUB25779 · Substance
- Active substance
- Bacillus Calmette-Guérin (Bcg), Tice
- Pharmaceutical form
- POWDER FOR INTRAVESICAL SUSPENSION
- Route of administration
- INTRAVESICAL USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 1350 mg milligram(s)
- Max treatment duration
- 147 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Merck Sharp & Dohme LLC
- Sponsor organisation
- Merck Sharp & Dohme LLC
- Address
- 126 East Lincoln Avenue
- City
- Rahway
- Postcode
- 07065-4607
- Country
- United States
Scientific contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Hema Dave
Public contact point
- Organisation
- Merck Sharp & Dohme LLC
- Contact name
- Hema Dave
Third parties 10
| Organisation | City, country | Duties |
|---|---|---|
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| Reify Health Inc. ORG-100049669
|
Boston, United States | Code 2 |
| Almac Clinical Technologies LLC ORG-100043036
|
Souderton, United States | Interactive response technologies (IRT) |
| Iqvia Limited ORG-100008655
|
Livingston, United Kingdom | Laboratory analysis |
| Quest Diagnostics Nichols Institute Inc. ORG-100012789
|
Chantilly, United States | Laboratory analysis |
| Azenta US Inc. ORG-100012907
|
Indianapolis, United States | Other |
| Exco Intouch Limited ORG-100040806
|
Nottingham, United Kingdom | E-data capture |
| Q Squared Solutions Holdings LLC ORG-100043288
|
Valencia, United States | Laboratory analysis |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Laboratory analysis |
| Parexel International Corporation ORG-100007310
|
Auburndale, United States | Other |
Locations
13 EU/EEA countries · 57 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruitment ended | 41 | 3 |
| Belgium | Ongoing, recruitment ended | 65 | 5 |
| Finland | Ongoing, recruitment ended | 5 | 1 |
| France | Ongoing, recruitment ended | 25 | 5 |
| Germany | Ongoing, recruitment ended | 45 | 5 |
| Greece | Ongoing, recruitment ended | 40 | 2 |
| Hungary | Ongoing, recruitment ended | 36 | 4 |
| Italy | Ongoing, recruitment ended | 58 | 10 |
| Netherlands | Ongoing, recruitment ended | 21 | 2 |
| Norway | Ongoing, recruitment ended | 16 | 2 |
| Poland | Ongoing, recruitment ended | 104 | 7 |
| Portugal | Ongoing, recruitment ended | 48 | 3 |
| Spain | Ongoing, recruitment ended | 55 | 8 |
| Rest of world
Peru, Puerto Rico, Colombia, Brazil, Taiwan, Canada, Guatemala, Japan, Switzerland, United Kingdom, Korea, Republic of, Turkey, Costa Rica, China, United States, Australia
|
— | 838 | — |
Investigational sites
Ordensklinikum Linz GmbH
Abteilung für Urologie und Andrologie, Fadingerstrasse 1, 4020, Linz
Medical University Of Vienna
Department of Urology, Waehringer Guertel 18-20, Alsergrund, Vienna
Gemeinnutzige Salzburger Landes kliniken Betriebsgesellschaft mbH
Department of Urology and Andrology, Muellner Hauptstrasse 48, 5020, Salzburg
Az Maria Middelares Gent
Integrated Cancer Center, Buitenring-Sint-Denijs 30, 9000, Gent
Universitair Ziekenhuis Gent
Department of Medical Oncology, Corneel Heymanslaan 10, 9000, Gent
AZORG Campus Aalst-Moorselbaan
Urological Department, Moorselbaan 164, 9300, Aalst
Antwerp University Hospital
Department of Urology, Drie Eikenstraat 655, 2650, Edegem
CHU UCL Namur
Oncology Department, Avenue Dr-Gaston-Therasse 1, 5530, Yvoir
Centre Hospitalier Universitaire De Lille
Urology, Rue Michel Polonovski, 59037, Lille Cedex
Centre Hospitalier Universitaire De Rennes
Urology, 2 Rue Henri Le Guilloux, 35033, Rennes Cedex 9
Centre Hospitalier Universitaire De Dijon
Urology, 14 Rue Paul Gaffarel, 21000, Dijon
Assistance Publique Hopitaux De Paris
NA, 51 Av Du Mal De Lattre De Tassigny, 94000, Creteil
Hospital Foch
Urology, 40 Rue Worth, 92150, Suresnes
University Hospital Jena KöR
Klinik und Poliklinik für Urologie, Am Klinikum 1, Lobeda, Jena
Klinikum Rechts Der Isar Der TU Muenchen AöR
Urologische Klinik und Poliklinik, Ismaninger Strasse 22, Au-Haidhausen, Munich
Klinikum Weiden
Klinik für Urologie, Andrologie und Kinderurologie, Soellnerstrasse 16, Scheibe, Weiden I D Opf
Barmherzige Brueder Trier gGmbH
Abteilung für Urologie und Kinderurologie Institut für Lithotripsie, Nord, Nordallee 1, Trier
Universitatsklinikum Wurzburg AöR
Klinik und Poliklinik für Urologie und Kinderurologie, Oberduerrbacher Strasse 6, Grombuehl, Wuerzburg
General University Hospital Of Larissa
University Urology Clinic, P. O. Box 1425, 411 10, Larissa
University General Hospital Attikon General Hospital Of West Attica H Agia Varvara
2nd University Propaedeutic Pathology clinic, Rimini 1, 124 61, Chaidari
University Of Pecs
Urológiai Klinika, Munkacsy Mihaly Utca 2, 7621, Pecs
University Of Debrecen
Urológiai Klinika, Nagyerdei Korut 98, 4032, Debrecen
Semmelweis University
Urológiai Klinika, Ulloi Ut 78/b, 1082, Budapest
University Of Szeged
Urológiai Klinika, Kalvaria Sugarut 57, 6725, Szeged
Central Hospital Of Bolzano
Oncologia medica, Via Lorenz Boehler 5, 39100, Bolzano
Ospedale Buccheri La Ferla di Palermo - Fatebenefratelli
UOC di Oncologia Medica, Via Messina Marine 197, 90123, Palermo
Azienda Sanitaria Usl Toscana Sud Est
UOC Oncologia Medica, Ospedale Area Aretina Nord, Via Pietro Nenni 20/22, Arezzo
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
U.O.C. Oncologia Medica, Largo Francesco Vito 1, 00168, Rome
Fondazione IRCCS Istituto Nazionale Dei Tumori
S.S. Oncologia Medica Genitourinaria, Via Giacomo Venezian 1, 20133, Milan
Azienda Sanitaria Locale 2 Lanciano Vasto Chieti
Unità Operativa Complessa di Urologia, Via Dei Vestini Snc, 66100, Chieti
Ospedale San Raffaele S.r.l.
Dipartimento di Medicina Oncologica, Via Olgettina 60, 20132, Milan
Careggi University Hospital
Urologia e Trapianti Renali, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department of Oncology, Via Ferdinando Magellano 1, 10128, Turin
Azienda Ospedaliera Universitaria Integrata Verona
U.O.C. Oncologia, Piazzale Aristide Stefani 1, 37126, Verona
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Medical Oncology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
University Hospital Maastricht
Internal Medicine, P. O. Box 5800, 6202 AZ, Maastricht
Akershus University Hospital
Urologisk Avdeling, Sykehusveien 25, 1474, Lørenskog
Stavanger University Hospital
Urologisk seksjon, Postboks 8100, 4068, Stavanger
Clinical Research Center Sp. z o.o. Medic-R sp.k.
CLINICAL RESEARCH CENTER Sp. z o.o. MEDIC-R SP. K., Ul. Feliksa Nowowiejskiego 5, 61-731, Poznan
MEDICAL CONCIERGE Centrum Medyczne
MEDICAL CONCIERGE Centrum Medyczne, Ul. Ulica Polnej Rozy 6/u2, 02-798, Warsaw
Wojewodzki Szpital Specjalistyczny Im. Janusza Korczaka W Slupsku Sp. z o.o.
Oddział Urologiczny, Ul. Hubalczykow 1, 76-200, Slupsk
Szpital Wojewodzki Im. Sw. Lukasza Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Tarnowie
Oddział urologii, Ul. Lwowska 178a, 33-100, Tarnow
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu
Klinika Urologii i Onkologii Urologicznej, Ul. Borowska 213, 50-556, Wroclaw
Medicover Integrated Clinical Services Sp. z o.o.
MICS Centrum Medyczne Toruń, Ul. Stefana Batorego 18/22, 87-100, Torun
Wojewodzki Szpital Im. Sw.Ojca Pio W Przemyslu
Oddział onkologiczny z Pododdziałem dziennej chemioterapii, Ul. Monte Cassino 18, 37-700, Peremyshl
Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.
Serviço de Urologia, Rua Dr. Antonio Bernardino De Almeida, 4200-072, Porto
Centro Hospitalar Universitario De Lisboa Norte E.P.E.
Serviço de Oncologia Médica, Avenida Professor Egas Moniz, 1649-035, Lisbon
CCAB Centro Clinico Academico Braga Associacao
Serviço de Urologia, Lugar De Sete Fontes S Victor, 4710-243, Braga
Hospital Universitario Lucus Augusti
Department of Urology, Calle Ulises Romero 1, 27003, Lugo
Hospital Universitario Y Politecnico La Fe
Medical Oncology, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Universitario Ramon Y Cajal
Department of Urology, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
MD Anderson Cancer Center
Medical Oncology, Calle De Arturo Soria Nº 270, 28033, Madrid
Fundacio Puigvert
Department of Urology, Cartagena 340-350, 8025, Barcelona
Hospital Universitario La Paz
Department of Urology, Paseo Castellana 261, 28046, Madrid
Hospital General Universitario Gregorio Maranon
Oncología Médica, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Quironsalud Madrid
Medical Oncology, Calle De Diego De Velazquez 1, 28223, Pozuelo De Alarcon
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2018-12-13 | 2019-02-14 | 2024-10-31 | ||
| Belgium | 2018-12-19 | 2019-02-18 | 2024-10-31 | ||
| Finland | 2018-12-19 | 2020-11-04 | 2023-05-15 | ||
| France | 2021-09-10 | 2021-10-13 | 2024-10-31 | ||
| Germany | 2019-04-02 | 2019-04-10 | 2024-10-31 | ||
| Greece | 2019-05-03 | 2019-07-09 | 2024-10-31 | ||
| Hungary | 2021-08-24 | 2021-10-05 | 2024-10-31 | ||
| Italy | 2019-04-08 | 2019-06-19 | 2024-10-31 | ||
| Netherlands | 2019-05-08 | 2019-08-13 | 2024-10-31 | ||
| Norway | 2019-01-03 | 2021-07-15 | 2023-11-01 | ||
| Poland | 2019-02-06 | 2019-04-23 | 2024-10-31 | ||
| Portugal | 2019-01-24 | 2019-09-05 | 2024-10-31 | ||
| Spain | 2018-11-27 | 2019-03-06 | 2024-10-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 163 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol signature page_for publication | 06 |
| Protocol (for publication) | D1_Protocol_2022-501817-29_GRC_EL_SM06_for pub | 07R |
| Protocol (for publication) | D1_Protocol_2022-501817-29_SM06_for pub | 07R |
| Protocol (for publication) | D4_Copyright statement_AUT_EN_SM07_for pub- | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_DEU_EN_SM07_for pub- | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_EN_SM07_for pub | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_ESP_EN_SM07_for pub | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_FRA_EN_SM07_for pub__ | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_GRC_EN_SM07_for pub-- | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_HUN_EN_SM07_for pub_ | 04DEC2024 |
| Protocol (for publication) | D4_Copyright statement_ITA_EN_SM07__for pub | 04DEC2024 |
| Recruitment arrangements (for publication) | CTIS Placeholder document 3475-676 | 21FEB2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Proced_ESP_ES_SM06_for pub | 24OCT2024 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_AUT_for pub | 27APR2023 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_BEL_EN_all_for pub | 1-0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_DEU_EN_SM06_for pub | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_FIN_Finnish_for pub | 11SEP2018 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_FRA_FR_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_GRC_EN_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_HUN_EN_for pub | v1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and IC Procedure_NLD_EN_for pub | v1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and ICF Procedure_NOR_EN_for pub | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements and Informed Consent Procedure_POL_Polish_for pub | 23OCT2018 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_BEL_FR_for pub | 11SEP2018 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_BEL_NL_for pub | 11SEP2018 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_ESP_ES_for pub | 10AUG2018 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_FRA_FR_for pub | 03MAR2021 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_GRC_EL_for pub | 08Nov2022 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_PRT_Portuguese_for pub | 18SEP2018 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Brochure_GRC_EL_for pub | 03 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Leave Behind Flyer_ESP_ES_for pub | 25Nov2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_AUT_German_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_BEL_EN_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_BEL_FR_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Master Tissue Brochure_BEL_NL_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_AUT_German_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_BCG_DEU_DE_for pub | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_BEL_EN_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_BEL_FR_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_BEL_NL_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_DEU_DE_for pub | 30Oct2020 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_ESP_ES_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_FIN_Finnish_for pub | 30OCT2020 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_FIN_Swedish_for pub | 30OCT2020 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_HUN_HU_for pub | 03 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_NOR_NN_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Brochure_PRT_Portuguese_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Flyer_BCGInformation_PRT_Portuguese_for pub | 2.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Patient Letter_ESP_ES_for pub | 25Nov2019 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_AUT_German_for pub | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_BEL_EN_for pub | 2 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_BEL_FR_for pub | 2 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_BEL_NL_for pub | 2 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_GRC_EL_for pub | 00 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Poster_PRT_Portuguese_for pub | 2.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Social Media_NLD_NL_for pub | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Doc Subject Recruitment_NLD_NL_SM06_for pub | 3 |
| Recruitment arrangements (for publication) | K2_Recruitment DocPoster_DEU_DE_for pub | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment_Doc Patient Brochure_NOR_NN_for pub | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_adults_GRC_EL_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_AUT_German_for pub | 02 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_BEL_EN_for pub | 0.04 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_BEL_FR_for pub | 0.04 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_BEL_NL_for pub | 0.04 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_DEU_DE_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_ESP_ES_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_FRA_FR_for pub | 03R |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_HUN_HU_for pub | v02 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_ITA_DE_0355_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_ITA_IT_for pub | v03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_NLD_NL_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_NOR_Norwegian_for publication | 18Oct2022 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_POL_PL_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR consent_PRT_Portuguese_for pub | 03 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR data privacy_ITA_DE_0355_for pub | 08MAY2023 |
| Subject information and informed consent form (for publication) | L1_ICF_FBR data privacy_ITA_IT_for pub | 08MAY2023 |
| Subject information and informed consent form (for publication) | L1_ICF_Genetic consent_BCG Naive_HUN_HU_SM06_for pub | 02 |
| Subject information and informed consent form (for publication) | L1_ICF_Genetic consent_BCG Post-induction_HUN_HU_SM06_for pub | v02 |
| Subject information and informed consent form (for publication) | L1_ICF_Genetic consent_PRT_Portuguese_for pub | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_0701_PRT_PT_SM16_for pub | AM02v2-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_0702_PRT_PT_SM16_for pub | AM02v2-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_ESP_ES_SM07_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_GRC_EL_SM07_for pub | AM02v2.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_HUN_HU_SM16_for pub | AM02v2-01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_ITA_IT_SM16-RFI003_for pub | AM02v2-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_POL_PL_SM16_for pub | AM02v2-03R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Naive_PRT_PT_SM16_for pub | AM02v2-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_0701_PRT_PT_SM16_for pub | AM04v4-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_0702_PRT_PT_SM16_for pub | AM04v4-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_DEU_DE_SM16_for pub | AM04v4-03R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_ESP_ES_SM07_for pub | AM04v4.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_GRC_EL_SM16_for pub | AM04v4-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_HUN_HU_SM16_for pub | AM04v2-01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_ITA_IT_SM16-RFI003_for pub | AM04v4-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_POL_PL_SM16_for pub | AM04v4-03R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent BCG Post-induction_PRT_PT_SM16_for pub | AM04v4-03 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_BEL_EN_SM07_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_BEL_FR_SM07_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_BEL_NL_SM07_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_DEU_DE_SM06_for pub | AM02v2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_FIN_FI_SM06_for pub | AM02v2.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_ITA_DE_0355_for pub | AM01v1.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_NLD_NL_SM07_for pub | AM02v2.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Naive_NOR_NN_SM06_for pub | AM02v2.01 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post induction_NLD_NL_SM07_for pub | AM04v4.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post-ind_BEL_FR_SM07_for pub | AM04v4.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post-induction_BEL_EN_SM07_for pub | AM04v4.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post-induction_BEL_NL_SM07_for pub | AM04v4.02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post-induction_FIN_FI_for pub | AM03v3.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Post-Induction_ITA_DE_0355_for pub | AM03v3.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_BCG Treated_NOR_NN_for pub | AM03 v3.02 |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_Cohort A_AUT_DE_SM06_for pub | 4.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_Cohort A_FRA_FR_SM16-RFI002_for pub | AM02v2-03R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_Cohort B_AUT_DE_SM06_for pub | 2.01R |
| Subject information and informed consent form (for publication) | L1_ICF_Main consent_Cohort B_FRA_FR_SM07-RFI005_for pub | AM02V2-02R |
| Subject information and informed consent form (for publication) | L1_ICF_Main data privacy_ITA_DE_0355_for pub | 08MAY2023 |
| Subject information and informed consent form (for publication) | L1_ICF_Main data privacy_ITA_IT_SM06_for pub | 24OCT2024 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_add crossborder_DEU_DE_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_addendum_Rechallenge_DEU_DE_0259_for pub | 00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_DILI sample_ITA_DE_0355_for pub | 08MAY2023 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_DILI sample_ITA_IT_SM06_for pub | 23OCT2024 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_naive_BEL_EN_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_naive_BEL_FR_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_naive_BEL_NL_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_post-induction_BEL_EN_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_post-induction_BEL_FR_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_Greenphire adults_post-induction_BEL_NL_SM07-RFI004_for pub | 0-00 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_pregnancy follow-up_PRT_Portuguese_for pub | 01 |
| Subject information and informed consent form (for publication) | L1_ICF_Optional_withdrawal_PRT_Portuguese_for_pub | 01 |
| Subject information and informed consent form (for publication) | L1_Patient contacts per site_0052_AUT_DE_for pub | 16JAN2024R |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_V914 INTRAVESICAL-BLADDER CANCER Merck_NSM03_for pub | 20MAR2025 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC RSI_V914 INTRAVESICAL-BLADDER CANCER Merck_SM12_for pub | 21MAY2024 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_OncoTICE_SM06_for pub | 08FEB2022 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC quality_OncoTICE_MSD Australia Pty Ltd_for publication | 23NOV2016 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29 _HUN_HU_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_BEL_DE_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_BEL_EN_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_BEL_FR_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_BEL_NL_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_ESP_ES_SM06_for pub | 2.0_PA07 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_FRA_FR_SM06_for pub | 21OCT2024 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_GRC_EL_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_ITA_IT_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_NOR_NN_SM06_for pub | 2 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_POL_PL_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-501817-29_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_2022-50187-29_NLD_NL_SM06_for pub | 2.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_AUT_DE_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_PPLS_DEU_DE_2022-501817-29_for pub | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_2022-501817-29_AUT_DE_SM06_for pub | AM07R |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_2022-501817-29_PRT_PT_SM06_for pub | 22OCT2024R |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_AUT_English_for publication | 00 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_BEL_DE_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_BEL_EN_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_BEL_FR_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_BEL_NL_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_DEU_DE_for pub | 00 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_ESP_ES_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_FRA_FR_for pub | 2.1 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_GRC_EL_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_HUN_Hungarian_for pub | 03 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_ITA_IT_for pub | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Scientific Synopsis_POL_2022-501817-29-00_Polish_for publication | 09AUG2018 |
Application history
14 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-02-23 | Finland | Acceptable 2023-04-27
|
2023-04-27 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-05-24 | Finland | Acceptable 2023-08-09
|
2023-08-09 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-12-18 | Finland | Acceptable 2024-03-04
|
2024-03-04 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-04-15 | Acceptable | 2024-06-17 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-04-25 | Acceptable | 2024-05-08 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-06-24 | Finland | Acceptable | 2024-06-24 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2024-10-29 | Finland | Acceptable 2025-01-09
|
2025-01-09 |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-03-04 | Finland | Acceptable 2025-04-29
|
2025-04-29 |
| 9 | SUBSTANTIAL MODIFICATION | SM-12 | 2025-06-19 | Finland | Acceptable 2025-08-19
|
2025-08-19 |
| 10 | SUBSTANTIAL MODIFICATION | SM-13 | 2025-09-11 | Acceptable | 2025-10-02 | |
| 11 | SUBSTANTIAL MODIFICATION | SM-14 | 2025-09-25 | Acceptable | 2025-10-13 | |
| 12 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-10-15 | Finland | Acceptable | 2025-10-15 |
| 13 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-10-29 | Finland | Acceptable | 2025-10-29 |
| 14 | SUBSTANTIAL MODIFICATION | SM-16 | 2025-12-05 | Finland | Acceptable 2026-01-28
|
2026-01-28 |