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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03481634
Ethics application status
Date submitted
13/03/2018
Date registered
29/03/2018
Date last updated
4/05/2020

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

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

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


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 - BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
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 - Assessed with ETDRS visual acuity testing charts
Timepoint [1] 0 0
Baseline up to Week 52
Secondary outcome [2] 0 0
Proportion of patients maintained at q12w up to Weeks 52 and 100 - Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.
Timepoint [2] 0 0
Up to Week 100
Secondary outcome [3] 0 0
Proportion of patients maintained at q12w up to Week 52 and Week 100 within those patients that qualified for q12w at Week 36 - This outcome measure is pre-specified for brolucizumab treatment arms only
Timepoint [3] 0 0
Up to Week 100
Secondary outcome [4] 0 0
Change from baseline in BCVA at each visit up to Week 100 - Assessed with ETDRS visual acuity testing charts
Timepoint [4] 0 0
Baseline up to Week 100
Secondary outcome [5] 0 0
Average change from baseline in BCVA over the period Week 88 to Week 100 - Assessed with ETDRS visual acuity testing charts
Timepoint [5] 0 0
Baseline up to Week 100
Secondary outcome [6] 0 0
Average change from baseline in BCVA over the period Week 4 to Week 52/100 - Assessed with ETDRS visual acuity testing charts
Timepoint [6] 0 0
Baseline up to Week 100
Secondary outcome [7] 0 0
Average change from baseline in BCVA over the period Week 20 to Week 52/100 and Week 28 to Week 52/100 - Assessed with ETDRS visual acuity testing charts
Timepoint [7] 0 0
Baseline up to Week 100
Secondary outcome [8] 0 0
Gain in BCVA of =5, =10, and =15 ETDRS letters from baseline to each post-baseline visit - Assessed with ETDRS visual acuity testing charts
Timepoint [8] 0 0
Baseline up to Week 100
Secondary outcome [9] 0 0
Time to achieve gain in BCVA of =5, =10, and =15 ETDRS letters from baseline (or reaching a score of 84 or more) - Assessed with ETDRS visual acuity testing charts
Timepoint [9] 0 0
Baseline up to Week 100
Secondary outcome [10] 0 0
Loss in BCVA of =5, =10, and =15 ETDRS letters from baseline to each post-baseline visit - Assessed with ETDRS visual acuity testing charts
Timepoint [10] 0 0
Baseline up to Week 100
Secondary outcome [11] 0 0
Absolute BCVA =73 ETDRS letters at each post-baseline visit - Assessed with ETDRS visual acuity testing charts
Timepoint [11] 0 0
Baseline up to Week 100
Secondary outcome [12] 0 0
Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 - This outcome measure is pre-specified for brolucizumab treatment arms only
Timepoint [12] 0 0
Up to Week 100
Secondary outcome [13] 0 0
Proportion of 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 - This outcome measure is pre-specified for brolucizumab treatment arms only
Timepoint [13] 0 0
Up to Week 100
Secondary outcome [14] 0 0
Proportion of patients with disease activity at Week 32 (eg =5 letters loss in BCVA compared to Week 28) - This outcome measure is pre-specified for brolucizumab treatment arms only
Timepoint [14] 0 0
Week 28, Week 32
Secondary outcome [15] 0 0
Change from baseline in central subfield thickness (CSFT) at each assessment visit - Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Timepoint [15] 0 0
Baseline up to Week 100
Secondary outcome [16] 0 0
Average change from baseline in CSFT over the period Week 40 through Week 52 / Week 88 through Week 100 - Assessed by SD-OCT
Timepoint [16] 0 0
Baseline up to Week 100
Secondary outcome [17] 0 0
Average change from baseline in CSFT over the period Week 4 to Week 52 / 96 - Assessed by SD-OCT
Timepoint [17] 0 0
Baseline up to Week 96
Secondary outcome [18] 0 0
Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit - Assessed by SD-OCT
Timepoint [18] 0 0
Baseline up to Week 100
Secondary outcome [19] 0 0
Change from baseline in central subfield thickness-neurosensory (CSFTns) at each assessment visit - Assessed by SD-OCT
Timepoint [19] 0 0
Baseline up to Week 100
Secondary outcome [20] 0 0
Average change from baseline in CSFTns over the period Week 40 through Week 52 / Week 88 through Week 100 - Assessed by SD-OCT
Timepoint [20] 0 0
Baseline up to Week 100
Secondary outcome [21] 0 0
Average change from baseline in CSFTns over the period Week 4 through Week 52 / 100 - Assessed by SD-OCT
Timepoint [21] 0 0
Baseline up to Week 100
Secondary outcome [22] 0 0
Proportion of patients with presence of subretinal fluid (SRF) at each assessment visit - Assessed by SD-OCT, angiography, and/or color fundus photography
Timepoint [22] 0 0
Baseline up to Week 100
Secondary outcome [23] 0 0
Proportion of patients with presence of intraretinal fluid (IRF) at each assessment visit - Assessed by SD-OCT, angiography, and/or color fundus photography
Timepoint [23] 0 0
Baseline up to Week 100
Secondary outcome [24] 0 0
Proportion of patients with simultaneous absence of SRF and IRF at each assessment visit - Assessed by SD-OCT, angiography, and/or color fundus photography
Timepoint [24] 0 0
Baseline up to Week 100
Secondary outcome [25] 0 0
Proportion of patients with presence of leakage on fluorescein angiography (FA) at Weeks 52 and 100 - Assessed by SD-OCT, angiography, and/or color fundus photography
Timepoint [25] 0 0
Up to Week 100
Secondary outcome [26] 0 0
Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) score at each assessment visit - The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative
Timepoint [26] 0 0
Baseline up to Week 100
Secondary outcome [27] 0 0
Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52 and Week 100 - ETDRS-DRSS
Timepoint [27] 0 0
Baseline up to Week 100
Secondary outcome [28] 0 0
Change from baseline in patient reported outcomes (VFQ-25) total and subscale scores up to Week 100 - The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains
Timepoint [28] 0 0
Baseline up to Week 100

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
Gender
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
Active, not recruiting
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)
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
Provincia De Cordoba
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
Ciudad Autonoma de Bs As
Country [23] 0 0
Argentina
State/province [23] 0 0
Cordoba
Country [24] 0 0
Austria
State/province [24] 0 0
Graz
Country [25] 0 0
Austria
State/province [25] 0 0
Innsbruck
Country [26] 0 0
Austria
State/province [26] 0 0
Vienna
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Colombia
State/province [29] 0 0
Antioquia
Country [30] 0 0
Colombia
State/province [30] 0 0
Bogota
Country [31] 0 0
Israel
State/province [31] 0 0
Haifa
Country [32] 0 0
Israel
State/province [32] 0 0
Jerusalem
Country [33] 0 0
Israel
State/province [33] 0 0
Kfar Saba
Country [34] 0 0
Israel
State/province [34] 0 0
Petach Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Rehovot
Country [36] 0 0
Israel
State/province [36] 0 0
Tel Aviv
Country [37] 0 0
Italy
State/province [37] 0 0
CH
Country [38] 0 0
Italy
State/province [38] 0 0
CT
Country [39] 0 0
Italy
State/province [39] 0 0
MI
Country [40] 0 0
Italy
State/province [40] 0 0
PD
Country [41] 0 0
Italy
State/province [41] 0 0
RM
Country [42] 0 0
Japan
State/province [42] 0 0
Aichi
Country [43] 0 0
Japan
State/province [43] 0 0
Fukuoka
Country [44] 0 0
Japan
State/province [44] 0 0
Hyogo
Country [45] 0 0
Japan
State/province [45] 0 0
Ibaragi
Country [46] 0 0
Japan
State/province [46] 0 0
Ibaraki
Country [47] 0 0
Japan
State/province [47] 0 0
Kagoshima
Country [48] 0 0
Japan
State/province [48] 0 0
Nagano
Country [49] 0 0
Japan
State/province [49] 0 0
Saitama
Country [50] 0 0
Japan
State/province [50] 0 0
Tochigi
Country [51] 0 0
Japan
State/province [51] 0 0
Tokyo
Country [52] 0 0
Japan
State/province [52] 0 0
Kumamoto
Country [53] 0 0
Japan
State/province [53] 0 0
Osaka
Country [54] 0 0
Netherlands
State/province [54] 0 0
Amsterdam
Country [55] 0 0
Netherlands
State/province [55] 0 0
Leiden
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
Country [57] 0 0
Netherlands
State/province [57] 0 0
Tilburg
Country [58] 0 0
Portugal
State/province [58] 0 0
Coimbra
Country [59] 0 0
Portugal
State/province [59] 0 0
Leiria
Country [60] 0 0
Portugal
State/province [60] 0 0
Porto
Country [61] 0 0
Portugal
State/province [61] 0 0
Santa Maria da Feira
Country [62] 0 0
Portugal
State/province [62] 0 0
Vila Franca de Xira
Country [63] 0 0
Puerto Rico
State/province [63] 0 0
Arecibo
Country [64] 0 0
Spain
State/province [64] 0 0
Castilla Y Leon
Country [65] 0 0
Spain
State/province [65] 0 0
Catalunya
Country [66] 0 0
Spain
State/province [66] 0 0
Comunidad Valenciana
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Santa Cruz de Tenerife
Country [69] 0 0
Spain
State/province [69] 0 0
Zaragoza
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Surrey
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Birmingham
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Hull
Country [73] 0 0
United Kingdom
State/province [73] 0 0
London
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment
of patients with visual impairment due to diabetic macular edema (DME).
Trial website
https://clinicaltrials.gov/show/NCT03481634
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

Summary results
Other publications