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Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KESTREL)

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ClinicalTrials.gov Identifier: NCT03481634
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

March 13, 2018
March 29, 2018
November 2, 2018
July 23, 2018
August 3, 2020   (Final data collection date for primary outcome measure)
Change from baseline in best-corrected visual acuity (BCVA) at Week 52 [ Time Frame: Baseline, Week 52 ]
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Same as current
Complete list of historical versions of study NCT03481634 on ClinicalTrials.gov Archive Site
  • Average change from baseline in BCVA over the period Week 40 through Week 52 [ Time Frame: Baseline up to Week 52 ]
    Assessed with ETDRS visual acuity testing charts
  • Proportion of patients maintained at q12w up to Weeks 52 and 100 [ Time Frame: Up to Week 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.
  • Proportion of patients maintained at q12w up to Week 52 and Week 100 within those patients that qualified for q12w at Week 36 [ Time Frame: Up to Week 100 ]
    This outcome measure is pre-specified for brolucizumab treatment arms only
  • Change from baseline in BCVA at each visit up to Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Average change from baseline in BCVA over the period Week 88 to Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Average change from baseline in BCVA over the period Week 4 to Week 52/100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Average change from baseline in BCVA over the period Week 20 to Week 52/100 and Week 28 to Week 52/100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Time to achieve gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more) [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Loss in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Absolute BCVA ≥73 ETDRS letters at each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts
  • Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) and Week 100 [ Time Frame: Up to Week 100 ]
    This outcome measure is pre-specified for brolucizumab treatment arms only
  • 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 [ Time Frame: Up to Week 100 ]
    This outcome measure is pre-specified for brolucizumab treatment arms only
  • Proportion of patients with disease activity at Week 32 (eg ≥5 letters loss in BCVA compared to Week 28) [ Time Frame: Week 28, Week 32 ]
    This outcome measure is pre-specified for brolucizumab treatment arms only
  • Change from baseline in central subfield thickness (CSFT) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
  • Average change from baseline in CSFT over the period Week 40 through Week 52 / Week 88 through Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT
  • Average change from baseline in CSFT over the period Week 4 to Week 52 / 96 [ Time Frame: Baseline up to Week 96 ]
    Assessed by SD-OCT
  • Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT
  • Change from baseline in central subfield thickness-neurosensory (CSFTns) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT
  • Average change from baseline in CSFTns over the period Week 40 through Week 52 / Week 88 through Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT
  • Average change from baseline in CSFTns over the period Week 4 through Week 52 / 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT
  • Proportion of patients with presence of subretinal fluid (SRF) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography
  • Proportion of patients with presence of intraretinal fluid (IRF) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography
  • Proportion of patients with simultaneous absence of SRF and IRF at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography
  • Proportion of patients with presence of leakage on fluorescein angiography (FA) at Weeks 52 and 100 [ Time Frame: Up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography
  • Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) score at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative
  • 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 [ Time Frame: Baseline up to Week 100 ]
    ETDRS-DRSS
  • Change from baseline in patient reported outcomes (VFQ-25) total and subscale scores up to Week 100 [ Time Frame: Baseline 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
Same as current
Not Provided
Not Provided
 
Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
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
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).
In this 2-year, randomized, double-masked, multicenter, active controlled study, consenting patients will be randomized in a 1:1:1 ratio to one of the three treatment arms (Brolucizumab 3 mg, Brolucizumab 6 mg, or Aflibercept 2 mg) and attend 28 planned visits.
Interventional
Phase 3
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Diabetic Macular Edema
  • Drug: Brolucizumab
    Intravitreal injection
    Other Name: RTH258, ESBA1008
  • Drug: Aflibercept
    Intravitreal injection
    Other Name: Eylea
  • Experimental: Brolucizumab 3 mg
    Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule
    Intervention: Drug: Brolucizumab
  • Experimental: Brolucizumab 6 mg
    Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule
    Intervention: Drug: Brolucizumab
  • Active Comparator: Aflibercept 2 mg
    Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks
    Intervention: Drug: Aflibercept
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
534
Same as current
July 5, 2021
August 3, 2020   (Final data collection date for primary outcome measure)

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

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

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Australia,   Austria,   Canada,   Israel,   Netherlands,   Puerto Rico,   Spain,   United Kingdom,   United States
 
 
NCT03481634
CRTH258B2301
2017-004742-23 ( EudraCT Number )
Not Provided
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Plan Description:

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.

Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP