Clinical trial NCT03481660: A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
Official title: A Two-Year, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Macular Edema
Keywords: Diabetic Macular Edema
intravitreal injection
brolucizumab
aflibercept
double-masked
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a Phase III, randomized, double-masked, multi-center, active-controlled, two-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with visual impairment due to diabetic macular edema (DME).

Detailed description: The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 96). The baseline visit was defined as Day 1/Visit 1, and end of treatment visit as Visit 27 (Week 96). After the last treatment visit, there was a post-treatment follow-up period from Week 96 to Week 100 and an exit visit at Week 100. Subjects were assigned to one of two treatment arms in a 1:1 ratio: brolucizumab 6 mg/0.05 mL (5 loading doses each administered every 6 weeks (q6w) during loading phase then q12w/q8w during maintenance phase with an option to extend treatment interval by 4 weeks during the second year) or aflibercept 2 mg/0.05 mL (5 loading doses each administered every 4 weeks (q4w) during loading phase then q8w during maintenance phase).

Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Week 32 and Week 36, i.e., 8 and 12 weeks after the end of the loading phase for subjects receiving brolucizumab, and at Week 48, Week 60 and Week 72 (i.e., every 12 weeks). In the brolucizumab arm, subjects who qualified for q12w during this initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at any of the subsequent DAA visits, in which case subjects were switched to a q8w treatment interval until Week 72.

A one-time disease stability assessment was performed by the masked investigator at Week 72 in both treatment arms with the purpose of evaluating the potential for treatment interval extension by 4 weeks. The subjects in the brolucizumab arm who demonstrated disease stability in the one-time assessment at Week 72 under their current assigned treatment regimen (q12w or q8w) were considered for treatment interval extension. To evaluate the adequacy of the individualized q8w, q12w or q16w treatment intervals in the brolucizumab arm, DAAs were performed at every visit from Week 72 up to and including Week 96 (i.e., every 4 weeks) and subjects had their treatment interval modified accordingly. If after Week 72 disease activity had been identified by the masked investigator at a scheduled treatment visit (according to the subject specific treatment schedule q12w or q16w) the subject was assigned to q8w treatment schedule.

Eligibility criteria: Key Inclusion Criteria:

General

* Patients must give written informed consent before any study related assessments are performed
* Patients with type 1 or type 2 diabetes mellitus and HbA1c of =\< 10% at screening
* Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study

Study Eye

* Visual impairment due to DME with:

  1. BCVA score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320), at screening and baseline
  2. DME involving the center of the macula, with central subfield retinal thickness (measured from RPE to ILM inclusively) of \>= 320 micrometers (μm) on SD-OCT at screening If both eyes are eligible, the eye with the worse visual acuity will be selected for study eye. However, the investigator may select the eye with better visual acuity, based on medical reasons or local ethical requirements.

     Key Exclusion Criteria:
* Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye
* Active proliferative diabetic retinopathy in the study eye as per the investigator
* Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g., cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
* Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
* Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
* Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) \> 25 millimeters mercury (mmHg) on medication or according to investigator's judgment, at screening or baseline
* Neovascularization of the iris in the study eye at screening or baseline
* Evidence of vitreomacular traction in the study eye at screening or baseline which, in the opinion of the investigator, affect visual acuity

Primary outcomes:
measure: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye
timeFrame: Baseline, period Week 40 through Week 52
measure: (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100.
timeFrame: Week 52, Week 100
measure: (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36
timeFrame: Week 36, Week 52
measure: (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36
timeFrame: Week 36, Week 100
measure: (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76
timeFrame: Week 68, Week 76, Week 100
measure: (Brolucizumab Treatment Arm Only): Percentage of Participants Re-assigned and Maintained on q12w up to Week 100 Within the Patients on q8w at Week 68 and on q12w at Week 80
timeFrame: Week 68, Week 80, Week 100
measure: (Brolucizumab Treatment Arm Only): Number of Participants With Injections Per Planned Dosing Regimen (Every 8, 12 or 16 Weeks)
timeFrame: Week 100
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Each Visit up to Week 100 for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 4 to Week 52/100 for the Study Eye
timeFrame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100
measure: Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 20 to Week 52/100 and Week 28 to Week 52/100 for the Study Eye
timeFrame: Baseline, period Week 20 through Week 52, period Week 20 through Week 100, period Week 28 through Week 52, period Week 28 through Week 100
measure: Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 88 to 100 for the Study Eye
timeFrame: Baseline, period Week 88 through Week 100
measure: Percentage of Participants Who Gained >= 5 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants Who Gained >= 10 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants Who Gained >= 15 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants Who Lost >= 5 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants Who Lost >= 10 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants Who Lost >= 15 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants With an Absolute Best Corrected Visual Acuity (BCVA) >= 73 ETDRS Letters at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Mean Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Average Mean Change From Baseline in Central Subfield Thickness (CSFT) Over the Period Week 40 Through Week 52 / Week 88 Through Week 100 for the Study Eye
timeFrame: Baseline, period Week 40 through Week 52, period Week 88 through Week 100
measure: Average Mean Change From Baseline in CSFT Over the Period Week 4 to Week 52 / 100 for the Study Eye
timeFrame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100
measure: Percentage of Participants With Normal CSFT Thickness (<280 Micrometers) at Each Post-baseline Visit for the Study Eye
timeFrame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Patients With Presence of Subretinal Fluid (SRF) in the Study Eye at Each Post-baseline Visit
timeFrame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Patients With Presence of Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit
timeFrame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Patients With Presence of Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit
timeFrame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100
measure: Percentage of Participants With Presence of Leakage on Fluorescein Angiography (FA) at Weeks 52 and 100
timeFrame: Week 52, Week 100
measure: Percentage of Participants With With >=2-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Percentage of Participants With With >=3-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Percentage of Participants With With >=2-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Percentage of Participants With With >=3-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Percentage of Participants With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS-DRSS Score of at Least 61 by Week 100
timeFrame: Week 100
measure: Number of Participants With Ocular and Non-ocular Adverse Events (AEs)
timeFrame: From randomization till 30 days safety follow-up, assessed up to 35 months.
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Composite Score
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - General Vision
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Ocular Pain
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Near Activities
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Distance Activities
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Social Functioning
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Mental Health
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Role Difficulties
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Dependency
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Driving
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Color Vision
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Peripheral Vision
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): General Health Rating
timeFrame: Baseline, Week 28, Week 52, Week 76, Week 100
measure: Systemic Brolucizumab Concentration
timeFrame: Up to Week 24
measure: Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm
timeFrame: Up to Week 100
measure: Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm - Adjusted for Pre-existing ADA Status
timeFrame: Up to Week 100
measure: Pre-existing ADA Status and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye
timeFrame: Up to Week 100
measure: Integrated ADA Status up to Week 100 and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye.
timeFrame: Up to Week 100
Other outcomes:
Locations:
city: Alken
country: Belgium
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
state: Rhone
city: Bobigny Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montauban
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Szombathely
country: Hungary
facility: Novartis Investigative Site
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Busan
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: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Petaling Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Shah Alam
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Cheboksary
country: Russian Federation
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Poprad
country: Slovakia
facility: Novartis Investigative Site
city: Trencin
country: Slovakia
facility: Novartis Investigative Site
city: Oerebro
country: Sweden
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Gaziantep
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: