Clinical trial NCT04720157: An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC
Official title: An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Lutetium-177 PSMA-617
177Lu-PSMA-617
Androgen receptor-directed therapy
ARDT
Androgen Deprivation Therapy
ADT
Metastatic Hormone sensitive prostate cancer
mHSPC
Radiographic progression free survival
rPFS
Prostate-specific membrane antigen
PSMA
Gallium-68 PSMA-11
68Ga-PSMA-11
Radioligand Therapy
RLT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Alliance Foundation Trials, LLC.
name: RTOG Foundation, Inc.
First posted: 2021-01-22
Enrollment: 1145
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patient randomized to SOC arm have an option to crossover to 177Lu-PSMA-617 treatment after rPFS
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants have been enrolled in 20 countries.

Detailed description: In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.

The randomization will be stratified according to the following three factors: disease volume (high v low), age \>= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.

Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD.

Prior treatment:

* Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
* Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.

Randomization period:

The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

Participants from both arms will also undergo PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =\< 7 days and enter the Post-treatment Follow-up .

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Eligibility criteria: Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Patients must be adults ≥18 years of age
3. Patients must have an ECOG performance status of 0 to 2
4. Patients must have a life expectancy \>9 months as determined by the study investigator
5. Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
6. Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
7. Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:

   1. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
   2. Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
   3. Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
8. Patients must have adequate organ function:

   * Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
   * Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
   * Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
9. Albumin ≥2.5 g/dL
10. Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
11. Patients must be:

Treatment naïve OR minimally treated with:

* Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
* If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued \> 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
* Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study.

1. Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
2. Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
3. Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
4. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
5. Ongoing participation in any other clinical trial
6. Use of other investigational drugs within 30 days prior to day of randomization
7. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
8. Transfusion for the sole purpose of making a participant eligible for study inclusion
9. Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
10. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
11. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
12. Active clinically significant cardiac disease defined as any of the following:

    * NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF \> 45% with improvement in symptoms to class \< 3.
    * History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
    * History of familial long QT syndrome or known family history of Torsades de Pointes
    * Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
13. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
14. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
15. Any condition that precludes raised arms position
16. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
17. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF

Primary outcomes:
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization until date of death from any cause, assessed up to 50 months (estimated final OS analysis)
measure: Prostate-specific antigen 90 (PSA90) response
timeFrame: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
measure: time to development of mCRPC
timeFrame: From date of randomization till End Of Treatment (EOT) or death, which ever happen first, assessed up to 50 months (estimated final OS analysis)
measure: Progression Free Survival (PFS)
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)
measure: second Progression Free Survival (PFS2)
timeFrame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)
measure: Change in nadir level of PSA lower than 0.2 ng/ml
timeFrame: From date of randomization till 30 days safety fup, whichever occur first, assessed up to 50 months (estimated final OS analysis)
measure: Time to radiographic soft tissue progression (TTSTP)
timeFrame: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to 50 months (estimated final OS analysis)
measure: Time to first symptomatic skeletal event (SSE).
timeFrame: From date of randomization till EOT or death, whichever happens first, assessed up to 50 months (estimated final OS analysis)
measure: Overall Response Rate (ORR)
timeFrame: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
measure: Disease Control Rate (DCR)
timeFrame: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
measure: Duration of Response (DOR)
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 50 months (estimated final OS analysis)
measure: Time to Response (TTR)
timeFrame: From date of randomization till 30 days safety fup, assessed up to 50 months (estimated final OS analysis)
measure: Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
timeFrame: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 50 months (estimated final OS analysis)
measure: European Quality of Life ( EuroQoL) -5 Domain 5 Level Scale (EQ-5D-5L)
timeFrame: From screening up till 30 day safety follow-up or week 48 of long term follow up for patient prematurely discontinued, assessed up to 50 months (estimated final OS analysis)
measure: Brief Pain Inventory-short Form (PBI-SF)
timeFrame: From screening up till 30 day safety follow-up or week 48 of long term follow up for patient prematurely discontinued, assessed up to 50 months (estimated final OS analysis)
measure: Number of participants with Treatment Emergent Adverse Events
timeFrame: From randomization till 30 days safety follow-up, assessed up to 50 months (estimated final OS analysis)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona Mayo Clinic Hospital
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: VA Greater LA Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of California LA
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Orange
country: United States
facility: Univ Cali Irvine ALS Neuromuscular
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Monica
country: United States
facility: Providence Saint Johns Health Ctr
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Anschutz Medical Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University-Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: VA Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Miami
country: United States
facility: Baptist Health Medical Group
state: Florida
city: Panama City
country: United States
facility: Florida Cancer Affiliates
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center LLC
state: Georgia
city: Honolulu
country: United States
facility: The Queens Medical Centre
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Hines
country: United States
facility: Hines VA Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel CCC At JH
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: Uni Of Michigan Health System
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaum Hosp
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Med Ctr
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: VA St Louis Health Care System
state: Missouri
city: Saint Louis
country: United States
facility: Wash U School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: Urology Cancer Center PC
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Ctr
state: New York
city: Rochester
country: United States
facility: Univ Of Rochester Cancer Ctr
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ Hosp
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh Cancer Institute
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Univ of Texas Southwest Med Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Houston
country: United States
facility: UT Health Science Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio Mays Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Onco Hemato Asso of SE Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kobe
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Kumamoto
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Yamagata
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Delft
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Gliwice
country: Poland
facility: Novartis Investigative Site
state: Slaskie
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Middlesbrough
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: