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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03481634




Registration number
NCT03481634
Ethics application status
Date submitted
13/03/2018
Date registered
29/03/2018

Titles & IDs
Public title
Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
Scientific title
A Two-year, Three-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
Secondary ID [1] 0 0
2017-004742-23
Secondary ID [2] 0 0
CRTH258B2301
Universal Trial Number (UTN)
Trial acronym
KESTREL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Brolucizumab
Treatment: Drugs - Aflibercept

Experimental: Brolucizumab 3 mg - Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule.

To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).

Experimental: Brolucizumab 6 mg - Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule.

To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).

Active comparator: Aflibercept 2 mg - Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks.

To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP).


Treatment: Drugs: Brolucizumab
Intravitreal injection

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

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Average Change From Baseline in BCVA Over the Period Week 40 Through Week 52
Timepoint [1] 0 0
Baseline and Week 40 through Week 52 (average)
Secondary outcome [2] 0 0
Patients Maintained at q12w - Probability of Maintaining on q12w
Timepoint [2] 0 0
Baseline (Week 0), Weeks 32, 36 and 48
Secondary outcome [3] 0 0
Patients Maintained at q12w (for Those Patients Who Qualified for q12w at Week 36) - Probability of Maintaining on q12w
Timepoint [3] 0 0
Weeks 36 and 48
Secondary outcome [4] 0 0
Change From Baseline in BCVA at Each Visit up to Week 52
Timepoint [4] 0 0
Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary outcome [5] 0 0
BCVA (Letters Read): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (FAS - LOCF)
Timepoint [5] 0 0
Baseline, and Week 88 through Week 100 (average)
Secondary outcome [6] 0 0
Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100 - Probability of Maintaining on q12w
Timepoint [6] 0 0
Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary outcome [7] 0 0
Secondary: Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100, Within Those Patients That Qualified for q12w at Week 36 - Probability of Maintaining on q12w
Timepoint [7] 0 0
Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary outcome [8] 0 0
Change From Baseline in Central Subfield Thickness (CSFT) at Each Visit up to Week 52 - Pairwise ANOVA Results
Timepoint [8] 0 0
Baseline up to week 52
Secondary outcome [9] 0 0
Central Subfield Thickness (CSFT) (Micrometers): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (Full Analysis Set - LOCF)
Timepoint [9] 0 0
Baseline, and Week 88 through Week 100 (average)
Secondary outcome [10] 0 0
Number of Patients With Presence of Subretinal Fluid (SRF) at Each Assessment Visit
Timepoint [10] 0 0
Baseline up to Week 52 and Week 100
Secondary outcome [11] 0 0
Number of Patients With Presence of Intraretinal Fluid (IRF) at Each Assessment Visit
Timepoint [11] 0 0
Baseline, up to Week 52 and Week 100
Secondary outcome [12] 0 0
Number of Patients With Presence of SRF and/or IRF in the Study Eye by Visit
Timepoint [12] 0 0
Baseline, up to Week 52 and Week 100
Secondary outcome [13] 0 0
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 52
Timepoint [13] 0 0
Week 52
Secondary outcome [14] 0 0
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 100
Timepoint [14] 0 0
Week 100
Secondary outcome [15] 0 0
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Timepoint [15] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [16] 0 0
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Timepoint [16] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [17] 0 0
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Timepoint [17] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [18] 0 0
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Timepoint [18] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [19] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Composite Score
Timepoint [19] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [20] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Vision
Timepoint [20] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [21] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Ocular Pain
Timepoint [21] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [22] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Near Activities
Timepoint [22] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [23] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Distance Activities
Timepoint [23] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [24] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Social Functioning
Timepoint [24] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [25] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Mental Health
Timepoint [25] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [26] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Role Difficulties
Timepoint [26] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [27] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Dependency
Timepoint [27] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [28] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Driving
Timepoint [28] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [29] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Color Vision
Timepoint [29] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [30] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Peripheral Vision
Timepoint [30] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [31] 0 0
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Health Rating
Timepoint [31] 0 0
Baseline, Weeks 28, 52, 76, 100
Secondary outcome [32] 0 0
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye
Timepoint [32] 0 0
Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Secondary outcome [33] 0 0
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)
Timepoint [33] 0 0
Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.

Eligibility
Key inclusion criteria
* Written informed consent before any assessment
* Patients with type 1 or type 2 diabetes mellitus and HbA1c of =10% at screening
* Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active proliferative diabetic retinopathy in the study eye
* Active intraocular or periocular infection or active intraocular inflammation in study eye
* Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
* Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
* Stroke or myocardial infarction during the 6-month period prior to baseline
* Uncontrolled blood pressure defined as a systolic value =160 mmHg or diastolic value =100 mmHg

Other protocol-specified inclusion/exclusion criteria may apply

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

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/10/2021
Sample size
Target
Accrual to date
Final
566
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parramatta
Recruitment hospital [3] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [4] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [5] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [6] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [7] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [8] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2150 - Parramatta
Recruitment postcode(s) [3] 0 0
2000 - Sydney
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3002 - Melbourne
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
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
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Provincia De Santa Fe
Country [21] 0 0
Argentina
State/province [21] 0 0
Caba
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Austria
State/province [23] 0 0
Graz
Country [24] 0 0
Austria
State/province [24] 0 0
Innsbruck
Country [25] 0 0
Austria
State/province [25] 0 0
Vienna
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Colombia
State/province [28] 0 0
Antioquia
Country [29] 0 0
Colombia
State/province [29] 0 0
Bogota
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
Country [31] 0 0
Israel
State/province [31] 0 0
Jerusalem
Country [32] 0 0
Israel
State/province [32] 0 0
Kfar Saba
Country [33] 0 0
Israel
State/province [33] 0 0
Petach Tikva
Country [34] 0 0
Israel
State/province [34] 0 0
Rehovot
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Aviv
Country [36] 0 0
Italy
State/province [36] 0 0
CH
Country [37] 0 0
Italy
State/province [37] 0 0
CT
Country [38] 0 0
Italy
State/province [38] 0 0
MI
Country [39] 0 0
Italy
State/province [39] 0 0
PD
Country [40] 0 0
Italy
State/province [40] 0 0
RM
Country [41] 0 0
Japan
State/province [41] 0 0
Aichi
Country [42] 0 0
Japan
State/province [42] 0 0
Fukuoka
Country [43] 0 0
Japan
State/province [43] 0 0
Hyogo
Country [44] 0 0
Japan
State/province [44] 0 0
Ibaragi
Country [45] 0 0
Japan
State/province [45] 0 0
Ibaraki
Country [46] 0 0
Japan
State/province [46] 0 0
Kagoshima
Country [47] 0 0
Japan
State/province [47] 0 0
Nagano
Country [48] 0 0
Japan
State/province [48] 0 0
Saitama
Country [49] 0 0
Japan
State/province [49] 0 0
Tochigi
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo
Country [51] 0 0
Japan
State/province [51] 0 0
Kumamoto
Country [52] 0 0
Japan
State/province [52] 0 0
Osaka
Country [53] 0 0
Netherlands
State/province [53] 0 0
Amsterdam
Country [54] 0 0
Netherlands
State/province [54] 0 0
Rotterdam
Country [55] 0 0
Netherlands
State/province [55] 0 0
Tilburg
Country [56] 0 0
Portugal
State/province [56] 0 0
Coimbra
Country [57] 0 0
Portugal
State/province [57] 0 0
Leiria
Country [58] 0 0
Portugal
State/province [58] 0 0
Porto
Country [59] 0 0
Portugal
State/province [59] 0 0
Santa Maria da Feira
Country [60] 0 0
Portugal
State/province [60] 0 0
Vila Franca de Xira
Country [61] 0 0
Puerto Rico
State/province [61] 0 0
Arecibo
Country [62] 0 0
Spain
State/province [62] 0 0
Castilla Y Leon
Country [63] 0 0
Spain
State/province [63] 0 0
Catalunya
Country [64] 0 0
Spain
State/province [64] 0 0
Comunidad Valenciana
Country [65] 0 0
Spain
State/province [65] 0 0
Barcelona
Country [66] 0 0
Spain
State/province [66] 0 0
Zaragoza
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Surrey
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Birmingham
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Hull
Country [70] 0 0
United Kingdom
State/province [70] 0 0
London
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Nottingham

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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 with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect 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?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03481634