NCT03528694

Brief Summary

This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,018

participants targeted

Target at P75+ for phase_3

Timeline
30mo left

Started May 2018

Longer than P75 for phase_3

Geographic Reach
11 countries

115 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress77%
May 2018Oct 2028

First Submitted

Initial submission to the registry

February 28, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

May 14, 2018

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 18, 2018

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 3, 2025

Completed
3.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 3, 2028

Expected
Last Updated

April 14, 2026

Status Verified

April 1, 2026

Enrollment Period

6.9 years

First QC Date

February 28, 2018

Last Update Submit

April 3, 2026

Conditions

Keywords

DurvalumabBCGMEDI4736NMIBCPD-L1DFSOS

Outcome Measures

Primary Outcomes (1)

  • The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC

    Disease-free survival using Investigator disease assessments.

    Up to 4 years

Secondary Outcomes (25)

  • To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of DFS 24 months

    Up to 4 years

  • To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of OS5

    Up to 7 years

  • To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of any disease-free survival

    Up to 7 years

  • To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of Time to MIBC and/or Metastatic Disease

    Up to 4 years

  • To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone with respect to time to cystectomy

    Up to 4 years

  • +20 more secondary outcomes

Study Arms (3)

Durvalumab plus BCG (induction + maintenance)

EXPERIMENTAL

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Biological: Durvalumab (MEDI4736)Biological: Bacillus Calmette-Guerin (BCG)

Durvalumab plus BCG (induction only)

EXPERIMENTAL

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Biological: Durvalumab (MEDI4736)Biological: Bacillus Calmette-Guerin (BCG)

BCG treatment (Standard of care therapy)

ACTIVE COMPARATOR

Bacillus Calmette-Guerrin (BCG) standard of care treatment

Biological: Bacillus Calmette-Guerin (BCG)

Interventions

Investigational product

Durvalumab plus BCG (induction + maintenance)Durvalumab plus BCG (induction only)

Standard of care

BCG treatment (Standard of care therapy)Durvalumab plus BCG (induction + maintenance)Durvalumab plus BCG (induction only)

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged at least 18 years
  • BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible)
  • Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following
  • T1 tumor
  • High grade/ G3 tumor
  • CIS
  • Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point)
  • Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible
  • No prior radiotherapy for bladder cancer
  • No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded

You may not qualify if:

  • Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)
  • Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium
  • Previous investigational product (IP) assignment in the present study
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
  • Patients with celiac disease controlled by diet alone
  • History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of IP and of low potential risk for recurrence during the study period
  • Adequately treated nonmelanoma skin cancer or lentigo maligna withoutevidence of disease
  • Adequately treated CIS without evidence of disease
  • Prostate cancer (tumor/node/metastasis stage) of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (120)

Research Site

Auchenflower, 4066, Australia

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Box Hill, 3128, Australia

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Brisbane, 4122, Australia

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Kogarah, 2217, Australia

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Orange, 2800, Australia

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Parkville, 3000, Australia

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Westmead, 2145, Australia

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Wollongong, 2500, Australia

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Linz, 4020, Austria

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Brussels, 1070, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Roeselare, 8800, Belgium

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Kingston, Ontario, K7L 3J7, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Chicoutimi, Quebec, G7H 5H6, Canada

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Montreal, Quebec, H2X 3E4, Canada

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Québec, Quebec, G1J 1Z4, Canada

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Amiens, 80054, France

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Angers, 49033, France

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Bordeaux, 33076, France

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Lyon, 69437, France

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Marseille, 13003, France

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Montpellier, 34295, France

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Strasbourg, 67098, France

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Suresnes, 92151, France

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Berlin, 10117, Germany

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Cologne, 50968, Germany

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Duisburg, 47169, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Marburg, 35043, Germany

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Mettmann, 40822, Germany

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Mühlheim An Der Ruhr, 45468, Germany

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München, 81377, Germany

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Münster, 48149, Germany

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Nürtingen, 72622, Germany

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Wesel, 46483, Germany

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Würselen, 52146, Germany

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Zirndorf, 90513, Germany

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Bunkyō City, 113-8603, Japan

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Fukuoka, 812-8582, Japan

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Hirosaki-shi, 036-8563, Japan

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Kanazawa, 920-8641, Japan

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Kita-gun, 761-0793, Japan

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Koshigaya-shi, 343-8555, Japan

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Kōtoku, 135-8550, Japan

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Matsuyama, 791-0280, Japan

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Miyazaki, 889-1692, Japan

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Nagasaki, 852-8501, Japan

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Nagoya, 467-0001, Japan

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Okayama, 700-8558, Japan

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Osaka, 541-8567, Japan

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Osaka, 545-8586, Japan

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Osakasayama-shi, 589-8511, Japan

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Sapporo, 060-8543, Japan

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Shinjuku-ku, 160-8582, Japan

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Toyama, 930-0194, Japan

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Tsukuba, 305-8576, Japan

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Yokohama, 232-0024, Japan

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Amsterdam, 1081 HV, Netherlands

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Breda, 4818 CK, Netherlands

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Utrecht, 3543 AZ, Netherlands

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Bialystok, 15-950, Poland

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Gdansk, 80-952, Poland

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Grudziądz, 86-300, Poland

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Koszalin, 75-581, Poland

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Piotrkow Trybunalski, 97-300, Poland

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Poznan, 61-731, Poland

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Warsaw, 02-005, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 50-556, Poland

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Wroclaw, 53-413, Poland

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Ivanovo, 153040, Russia

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Krasnoyarsk, 660133, Russia

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Moscow, 105077, Russia

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Moscow, 115280, Russia

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Moscow, 125367, Russia

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Nizhny Novgorod, 603074, Russia

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Obninsk, 249036, Russia

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Omsk, 644013, Russia

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Saint Petersburg, 191014, Russia

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Saint Petersburg, 194017, Russia

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Saint Petersburg, 194044, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 195271, Russia

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Saint Petersburg, 197758, Russia

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Vologda, 160012, Russia

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Yaroslavl, 150054, Russia

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Badajoz, 06008, Spain

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Barcelona, 08025, Spain

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Barcelona, 08036, Spain

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Barcelona, 08208, Spain

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Barcelona, 8003, Spain

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Elche(Alicante), 03202, Spain

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Madrid, 08035, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Oviedo, 33011, Spain

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Pamplona, 31008, Spain

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Pozuelo de Alarcón, 28223, Spain

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Seville, 41009, Spain

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Seville, 41014, Spain

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Valencia, 46014, Spain

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Valencia, 46026, Spain

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Birmingham, B15 2TH, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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Guildford, CU2 7XX, United Kingdom

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London, E1 1BB, United Kingdom

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London, NW1 2PG, United Kingdom

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London, SE1 9RT, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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Southampton, S016 6YD, United Kingdom

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Taunton, TA1 5DA, United Kingdom

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Related Publications (1)

  • De Santis M, Palou Redorta J, Nishiyama H, Krawczynski M, Seyitkuliev A, Novikov A, Guerrero-Ramos F, Zukov R, Kato M, Kawahara T, Goeman L, Puente J, Hellmis E, Powles T, Radziszewski P, Gust KM, Vasey P, Bigot P, Fradet Y, Hunting J, Armstrong J, Boulos S, Hois S, Shore ND; POTOMAC Investigators. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025 Nov 8;406(10516):2221-2234. doi: 10.1016/S0140-6736(25)01897-5. Epub 2025 Oct 17.

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

durvalumabBCG Vaccine

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsUrinary Bladder NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis VaccinesBacterial VaccinesVaccinesBiological ProductsComplex Mixtures

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 28, 2018

First Posted

May 18, 2018

Study Start

May 14, 2018

Primary Completion

April 3, 2025

Study Completion (Estimated)

October 3, 2028

Last Updated

April 14, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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