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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03273153




Registration number
NCT03273153
Ethics application status
Date submitted
1/09/2017
Date registered
6/09/2017
Date last updated
21/09/2022

Titles & IDs
Public title
A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
Scientific title
A Phase III, Open-Label, Multicenter, Two Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma
Secondary ID [1] 0 0
2016-004387-18
Secondary ID [2] 0 0
CO39722
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced BRAFV600 Wild-type Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cobimetinib
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Pembrolizumab

Experimental: Cobimetinib and Atezolizumab - Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.

Active comparator: Pembrolizumab - Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.


Treatment: Drugs: Cobimetinib
Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.

Treatment: Drugs: Atezolizumab
Atezolizumab 840 mg as IV infusion once in every 2 weeks.

Treatment: Drugs: Pembrolizumab
Pembrolizumab 200 mg as IV infusion once in every 3 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
Timepoint [1] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [1] 0 0
PFS as Determined by the Investigator
Timepoint [1] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [2] 0 0
Objective Response as Determined by the Investigator
Timepoint [2] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [3] 0 0
Objective Response as Determined by IRC
Timepoint [3] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Week 16
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From randomization up to approximately 3 years
Secondary outcome [6] 0 0
Duration of Objective Response Determined by the IRC
Timepoint [6] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [7] 0 0
Duration of Objective Response Determined by the Investigator
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
Two-year Landmark Survival
Timepoint [8] 0 0
At 2 years
Secondary outcome [9] 0 0
Change From Baseline in Health-related Quality of Life (HRQoL) Scores
Timepoint [9] 0 0
Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.
Secondary outcome [10] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [10] 0 0
Up to approximately 16 months
Secondary outcome [11] 0 0
Number of Participants With Abnormal Vital Signs
Timepoint [11] 0 0
From baseline up to approximately 3 years
Secondary outcome [12] 0 0
Number of Participants With Laboratory Abnormalities
Timepoint [12] 0 0
Up to approximately 16 months
Secondary outcome [13] 0 0
Plasma Concentration of Cobimetinib
Timepoint [13] 0 0
Days 1 and 15 of Cycle 1
Secondary outcome [14] 0 0
Serum Concentration of Atezolizumab
Timepoint [14] 0 0
Day 1 of Cycles 1, 2, and 3
Secondary outcome [15] 0 0
Percentage of Participants With Anti-drug Antibodies (ADAs)
Timepoint [15] 0 0
Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation

Eligibility
Key inclusion criteria
Disease-Specific Inclusion Criteria

* Histologically confirmed locally advanced and unresectable or metastatic melanoma
* Naive to prior systemic anti-cancer therapy for melanoma
* Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority
* A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study entry. If 20 slides are not available or the tissue block is not of sufficient size, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Age >=18 years at time of signing Informed Consent Form
* Ability to comply with the study protocol, in the investigator's judgment
* Histologically or cytologically confirmed BRAFV600 wild-type melanoma
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy >=3 months
* Adequate hematologic and end-organ function
* For women of childbearing potential: agreement to remain abstinent or use at least two forms of effective contraceptive with a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib and at least 5 months after the last dose of atezolizumab or pembrolizumab
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (e.g. condom), and agreement to refrain from donating sperm, for at least 3 months after the last dose of cobimetinib
* Willingness and ability of patients to report selected study outcomes (e.g., GHS and HRQoL) using an electronic device or paper backup questionnaires.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
General Exclusion Criteria

* Inability to swallow medications
* Malabsorption condition that would alter the absorption of orally administered medications
* Pregnancy, breastfeeding, or intention of becoming pregnant during the study
* History of severe hypersensitivity reactions to components of the cobimetinib, atezolizumab, or pembrolizumab formulations
* Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or systemic immunostimulatory/immunosuppresive medication
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Cancer-Related Exclusion Criteria
* Ocular melanoma
* Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation of needing such procedure while receiving study treatment
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
* Active or untreated central nervous system (CNS) metastases Exclusions Related to Cardiovascular Disease
* Unstable angina, new-onset angina within last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure classified as New York Heart Association Class II or higher
* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or <50%, whichever is lower
* Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic baseline hypertension consistently above 159/99 mmHg despite optimal medical management
* History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
* HIV infection
* Active tuberculosis infection
* Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of Cycle 1
* Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
* Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular Disease
* Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and Immunomodulatory Drugs
* Active or history of autoimmune disease or immune deficiency
* Prior allogeneic stem cell or solid organ transplantation
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1, Cycle 1 Exclusions Related to Other Medical Conditions or Medications
* Active malignancy (other than melanoma) or a prior malignancy within the past 3 years
* Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
* History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
* Proteinuria >3.5 gm/24 hr
* Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,TAS,WA
Recruitment hospital [1] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [2] 0 0
Townsville General Hospital - Douglas
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
4870 - Cairns
Recruitment postcode(s) [2] 0 0
4184 - Douglas
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New Hampshire
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
West Virginia
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Kortrijk
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Brazil
State/province [18] 0 0
RJ
Country [19] 0 0
Brazil
State/province [19] 0 0
RS
Country [20] 0 0
France
State/province [20] 0 0
Bobigny
Country [21] 0 0
France
State/province [21] 0 0
Bordeaux
Country [22] 0 0
France
State/province [22] 0 0
Dijon
Country [23] 0 0
France
State/province [23] 0 0
Grenoble
Country [24] 0 0
France
State/province [24] 0 0
Le Mans
Country [25] 0 0
France
State/province [25] 0 0
Lille
Country [26] 0 0
France
State/province [26] 0 0
Marseille
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France
State/province [27] 0 0
Nantes
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France
State/province [28] 0 0
Nice cedex 3
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Reims
Country [31] 0 0
France
State/province [31] 0 0
Rennes
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France
State/province [32] 0 0
Rouen
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France
State/province [33] 0 0
Toulouse
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France
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Villejuif
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Germany
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Dresden
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Germany
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Erfurt
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Gera
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Germany
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Hannover
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Germany
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Kiel
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Germany
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Mainz
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Germany
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Mannheim
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Germany
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Minden
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Germany
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München
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Germany
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Münster
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Germany
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Tübingen
Country [48] 0 0
Greece
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Athens
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Greece
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Pireaus
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Greece
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Thessaloniki
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Hungary
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Budapest
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Hungary
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Pecs
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Hungary
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Szeged
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Italy
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Campania
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Italy
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Emilia-Romagna
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Italy
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Lazio
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Italy
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Liguria
Country [58] 0 0
Italy
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Lombardia
Country [59] 0 0
Italy
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Piemonte
Country [60] 0 0
Italy
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Puglia
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Italy
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Toscana
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Italy
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Veneto
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Breda
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Netherlands
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Rotterdam
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Netherlands
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Sittard-Geleen
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Poland
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Gdansk
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Poland
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Lublin
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Poland
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Poznan
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Poland
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Szczecin
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Poland
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Warszawa
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Poland
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Wroclaw
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Russian Federation
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Moskovskaja Oblast
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Russian Federation
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St Petersburg
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Spain
State/province [78] 0 0
Barcelona
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Spain
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Islas Baleares
Country [80] 0 0
Spain
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LA Coruña
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Spain
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LAS Palmas
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Spain
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Navarra
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Spain
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Madrid
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Spain
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Sevilla
Country [85] 0 0
Spain
State/province [85] 0 0
Valencia
Country [86] 0 0
Spain
State/province [86] 0 0
Zaragoza
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Bristol
Country [88] 0 0
United Kingdom
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Edinburgh
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United Kingdom
State/province [89] 0 0
Leicester
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Stoke-On-Trent
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Swansea
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.