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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05349214




Registration number
NCT05349214
Ethics application status
Date submitted
8/04/2022
Date registered
27/04/2022

Titles & IDs
Public title
Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome
Scientific title
A Randomized, Double-blind, Placebo Controlled, 3-arm Multicenter Phase 3 Study to Assess the Efficacy and Safety of Ianalumab in Patients With Active Sjogren's Syndrome (NEPTUNUS-2)
Secondary ID [1] 0 0
2021-000424-35
Secondary ID [2] 0 0
CVAY736A2302
Universal Trial Number (UTN)
Trial acronym
NEPTUNUS-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sjogren Syndrome 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - VAY736
Treatment: Other - VAY736
Other interventions - Placebo

Experimental: Arm A - ianalumab exposure level 1

Experimental: Arm B - ianalumab exposure level 2

Placebo comparator: Arm C - placebo


Treatment: Other: VAY736
ianalumab s.c.

Treatment: Other: VAY736
ianalumab s.c.

Other interventions: Placebo
placebo s.c.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score at Week 48 as compared to placebo
Timepoint [1] 0 0
48 weeks
Secondary outcome [1] 0 0
Proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 48
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
Proportion of patients achieving ESSDAI<5 at Week 48
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
Proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 24
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Proportion of patients achieving meaningful improvement in the Sjogren's Syndrome Symptom Diary (SSSD) score at Week 48
Timepoint [4] 0 0
48 weeks
Secondary outcome [5] 0 0
Change from baseline in stimulated whole salivary flow rate at Week 48
Timepoint [5] 0 0
48 weeks
Secondary outcome [6] 0 0
Change from baseline in Physician's Global Assessment (PhGA) of disease activity at Week 48
Timepoint [6] 0 0
48 weeks
Secondary outcome [7] 0 0
Change from baseline in Patient's Global Assessment (PaGA) of disease activity at Week 48
Timepoint [7] 0 0
48 weeks
Secondary outcome [8] 0 0
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48
Timepoint [8] 0 0
48 weeks
Secondary outcome [9] 0 0
Proportion of patients achieving = 1 point or 15% reduction from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) at Week 48
Timepoint [9] 0 0
48 weeks

Eligibility
Key inclusion criteria
Inclusion criteria

* Signed informed consent must be obtained prior to participation in the study
* Women and men = 18 years of age
* Classification of Sjögren's syndrome according to the ACR/EULAR 2016 criteria
* Time since diagnosis of Sjögren's of = 7.5 years at screening
* Positive anti-Ro/SSA antibody at screening

* Patients negative for anti-Ro/SSA antibody are eligible, if they have a positive salivary gland biopsy confirmed by central expert review
* Enrollment of anti-Ro/SSA-negative patients will be limited up to =10% of the study population
* Screening ESSDAI score of = 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic.
* Stimulated whole salivary flow (sSF) rate of = 0.05 mL/min at screening
* Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study
* Patients taking hydroxychloroquine (= 400 mg/day), methotrexate (= 25 mg/week) or azathioprine (= 150 mg/day) alone or in combination, are allowed to continue their medication, and must have been on a stable dose for at least 30 days prior to randomization.
* Patients taking systemic corticosteroids have to be on a stable dose of = 10 mg/day predniso(lo)ne or equivalent for at least 30 days before randomization.
* Patients taking

* disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed in inclusion criterion #9 or
* the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterium glycosides (TG) must discontinue these medications at least 30 days prior to randomization, except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
* Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer3. Prior treatment with ianalumab
* Prior use of a B-cell depleting therapy other than ianalumab within 36 weeks prior to randomization or as long as B-cell count is less than the lower limit of normal or baseline value prior to receipt of previous B cell-depleting therapy (whichever is lower)
* Prior treatment with any of the following:

1. Within 24 weeks prior to randomization: iscalimab (anti CD-40 mAb), belimumab , abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins plasmapheresis;
2. Within 12 weeks prior to randomization: i.v. or oral cyclophosphamide, mycophenolate mofetil, i.v. or oral cyclosporine A or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors) unless explicitly allowed by protocol
* Use of corticosteroids (predniso(lo)ne or equivalent corticosteroid) at dose >10 mg/day
* Any one of the following laboratory values at screening:

* Hemoglobin levels < 8.0 g/dL
* White blood cells (WBC) count < 2.0 x 10E3/µL
* Platelet count < 80 x 10E3/µL
* Absolute neutrophil count (ANC) < 0.8 x 10E3/µL
* Active viral, bacterial or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection or of recurrent bacterial infections with encapsulated organisms
* History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug formulation (sucrose, L-histidine hydrochloride/ L-histidine, polysorbate 20)
* History of major organ, hematopoietic stem cell or bone marrow transplant
* Required regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study.
* Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the study
* Receipt of live/attenuated vaccine within a 4-week period prior to randomization
* History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer or Sjögren's related lymphoma), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
* History of sarcoidosis
* Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes mellitus), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study
* Chronic infection with hepatitis B (HBV) or hepatitis C (HCV) virus. Positive serology for hepatitis B surface antigen (HBsAg) excludes the subject.

* HBsAg negative subjects who are hepatitis B core antibody (HBcAb) positive are also excluded unless all of the following criteria are met:

1. HBV DNA is negative
2. hepatitis B monitoring is implemented - in these subjects, monthly testing of HBsAg and HBV DNA must be performed while on study treatment and at least every 12 weeks after end of treatment for the entire duration of safety follow-up.
3. Antiviral prophylaxis must be implemented before the first administration of the study treatment, and continued up to 12 months after end of study treatment. If antiviral therapy cannot be given or if the patient is not willing to comply with the antiviral treatment requirement, the patient is not eligible for the study.
* Hepatitis C: patients with positive hepatitis C antibody and HCV-RNA at screening are excluded. Chronic hepatitis C patients who have completed HCV anti-viral treatment must be HCV-RNA negative at least 12 weeks after treatment before randomization to be eligible. Cases of spontaneous HCV clearance should be discussed with sponsor before enrollment.
* Evidence of active tuberculosis (TB) infection is exclusionary. Patient with previously treated TB and previously treated or newly diagnosed latent TB may be eligible.
* Pregnant or nursing (lactating) women,
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational medication.
* Patients with a known history of non-compliance to medication, or who were unable or unwilling to complete PRO questionnaires, or who are unable or unwilling to use the device for collection of PROs.
* United States (and other countries, if locally required): Sexually active males, unless they agree to use barrier protection during intercourse with a woman of childbearing potential, while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended that female partners of male study participants use a second method of birth control.

Although ianalumab is not teratogenic and/or genotoxic, and not transferred to semen, male contraception is required, as requested by FDA.

Globally, for all sexually active males, contraception should be used in accordance with locally approved prescribing information of concomitant medications administered.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/05/2027
Actual
Sample size
Target
Accrual to date
Final
505
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS
Recruitment hospital [1] 0 0
Novartis Investigative Site - Maroochydore
Recruitment hospital [2] 0 0
Novartis Investigative Site - Woodville
Recruitment hospital [3] 0 0
Novartis Investigative Site - Hobart
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
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
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
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
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
San Miguel De Tucuman
Country [16] 0 0
Brazil
State/province [16] 0 0
BA
Country [17] 0 0
Brazil
State/province [17] 0 0
PR
Country [18] 0 0
Brazil
State/province [18] 0 0
SP
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Burgas
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Plovdiv
Country [21] 0 0
Bulgaria
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Sofia
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
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Nova Scotia
Country [24] 0 0
Canada
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Ontario
Country [25] 0 0
Canada
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Quebec
Country [26] 0 0
Chile
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Los Rios
Country [27] 0 0
Chile
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RM
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Chile
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Concepcion
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China
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Anhui
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China
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Chongqing
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China
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Jiangsu
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China
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Jiangxi
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China
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Jilin
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China
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Shanxi
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China
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Sichuan
Country [36] 0 0
China
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The Ningxia Hui Autonomous Reg
Country [37] 0 0
China
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Xinjiang
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China
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Zhejiang
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China
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Beijing
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China
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Shanghai
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China
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Tianjin
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China
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Xinxiang
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Colombia
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Antioquia
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Colombia
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Atlantico
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Colombia
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Santander
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Colombia
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Bogota
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France
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Angers Cedex 9
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France
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Brest
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France
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Le Kremlin Bicetre
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France
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Le Mans
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France
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Strasbourg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Hannover
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Germany
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Herne
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Germany
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Koeln
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Greece
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Athens
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Hungary
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Fejer
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Hungary
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Debrecen
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Hungary
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Eger
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Hungary
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Gyula
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Hungary
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Szeged
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India
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Gujarat
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India
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Karnataka
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India
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Maharashtra
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India
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New Delhi
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Israel
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Kfar Saba
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Israel
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Ramat Gan
Country [69] 0 0
Italy
State/province [69] 0 0
AN
Country [70] 0 0
Italy
State/province [70] 0 0
MI
Country [71] 0 0
Italy
State/province [71] 0 0
SA
Country [72] 0 0
Italy
State/province [72] 0 0
UD
Country [73] 0 0
Italy
State/province [73] 0 0
Napoli
Country [74] 0 0
Japan
State/province [74] 0 0
Aichi
Country [75] 0 0
Japan
State/province [75] 0 0
Fukuoka
Country [76] 0 0
Japan
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Hokkaido
Country [77] 0 0
Japan
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Kanagawa
Country [78] 0 0
Japan
State/province [78] 0 0
Mie
Country [79] 0 0
Japan
State/province [79] 0 0
Nagasaki
Country [80] 0 0
Japan
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Okayama
Country [81] 0 0
Japan
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Tokyo
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Mexico
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Sinaloa
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Mexico
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Yucatan
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Mexico
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Mexico
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Poland
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Dolnoslaskie
Country [86] 0 0
Poland
State/province [86] 0 0
Malopolskie
Country [87] 0 0
Poland
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Wielkopolskie
Country [88] 0 0
Poland
State/province [88] 0 0
Warszawa
Country [89] 0 0
Poland
State/province [89] 0 0
Wroclaw
Country [90] 0 0
Romania
State/province [90] 0 0
Brasov
Country [91] 0 0
Romania
State/province [91] 0 0
Bucharest
Country [92] 0 0
Romania
State/province [92] 0 0
Bucuresti
Country [93] 0 0
Romania
State/province [93] 0 0
Cluj-Napoca
Country [94] 0 0
Slovakia
State/province [94] 0 0
Bratislava
Country [95] 0 0
Slovakia
State/province [95] 0 0
Kosice
Country [96] 0 0
Slovakia
State/province [96] 0 0
Topolcany
Country [97] 0 0
Slovakia
State/province [97] 0 0
Zvolen
Country [98] 0 0
South Africa
State/province [98] 0 0
Western Cape
Country [99] 0 0
South Africa
State/province [99] 0 0
Stellenbosch
Country [100] 0 0
Spain
State/province [100] 0 0
Andalucia
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Spain
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Cantabria
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Spain
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Pontevedra
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Spain
State/province [103] 0 0
Barcelona
Country [104] 0 0
Spain
State/province [104] 0 0
Madrid
Country [105] 0 0
Spain
State/province [105] 0 0
Valencia
Country [106] 0 0
Sweden
State/province [106] 0 0
SE
Country [107] 0 0
Taiwan
State/province [107] 0 0
Kaohsiung
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taichung
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Doncaster
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United Kingdom
State/province [110] 0 0
Leeds
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Liverpool
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Newcastle Upon Tyme
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Swindon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05349214