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Trial record 1 of 1 for:    Novartis CRTH258B2301 Kestrel
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Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KESTREL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03481634
Recruitment Status : Active, not recruiting
First Posted : March 29, 2018
Last Update Posted : March 26, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 13, 2018
First Posted Date  ICMJE March 29, 2018
Last Update Posted Date March 26, 2020
Actual Study Start Date  ICMJE July 23, 2018
Estimated Primary Completion Date November 11, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
Official Title  ICMJE 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
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).
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Macular Edema
Intervention  ICMJE
  • Drug: Brolucizumab
    Intravitreal injection
    Other Name: RTH258, ESBA1008
  • Drug: Aflibercept
    Intravitreal injection
    Other Name: Eylea
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 5, 2020)
571
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2018)
534
Estimated Study Completion Date  ICMJE October 13, 2021
Estimated Primary Completion Date November 11, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Canada,   Colombia,   Israel,   Italy,   Japan,   Netherlands,   Portugal,   Puerto Rico,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03481634
Other Study ID Numbers  ICMJE CRTH258B2301
2017-004742-23 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2020

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