KITE: A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03481660
Collaborator
(none)
360
78
2
34.4
4.6
0.1

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

In this 2-year, randomized, double-masked, multicenter, active controlled study, consenting patients will be randomized in a 1:1 ratio to one of the two treatment arms and attend 28 planned visits.

Study Design

Study Type:
Interventional
Actual Enrollment :
360 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 27, 2018
Actual Primary Completion Date :
Jun 29, 2020
Actual Study Completion Date :
Jun 8, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Brolucizumab 6 mg

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

Drug: Brolucizumab
Intravitreal injection
Other Names:
  • RTH258, ESBA1008
  • Active Comparator: Aflibercept 2 mg

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

    Drug: Aflibercept
    Intravitreal injection
    Other Names:
  • Eylea
  • Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in best-corrected visual acuity (BCVA) at Week 52 [Baseline, Week 52]

      BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

    Secondary Outcome Measures

    1. Average change from baseline in BCVA over the period Week 40 through Week 52 [Baseline up to Week 52]

      Assessed with ETDRS visual acuity testing charts

    2. Proportion of patients maintained at q12w up to Weeks 52 and 100 [Up to Week 100]

      Positive treatment status is defined as IVT injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arm only.

    3. Proportion of patients maintained at q12w up to Week 52 within those patients that qualified for q12w at Week 36 [Up to Week 52]

      This outcome measure is pre-specified for brolucizumab treatment arm only.

    4. Change from baseline in BCVA at each visit up to Week 100 [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    5. Average change from baseline in BCVA over the period Week 4 to Week 52/100 [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    6. Average change from baseline in BCVA over the period Week 20 to Week 52/100 and Week 28 to Week 52/100 [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    7. Gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    8. Time to achieve gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more) [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    9. Loss in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    10. Absolute BCVA ≥73 ETDRS letters at each post-baseline visit [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    11. Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) [Up to Week 64]

    12. Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals), within those patients that qualified for q12w at Week 36 [Up to Week 64]

      This outcome measure is pre-specified for brolucizumab treatment arm only

    13. Proportion of patients maintained at q12w/q16w up to Week 100, within those patients that qualified for q12w at Week 36 [Up to Week 100]

      This outcome measure is pre-specified for brolucizumab treatment arm only

    14. Proportion of patients with disease activity at Week 32 (eg ≥5 letters loss in BCVA compared to Week 28) [Week 28, Week 32]

      This outcome measure is pre-specified for brolucizumab treatment arm only

    15. Proportion of patients maintained on q16w up to Week 100 within the patients on q12 at Week 68 and on q16w at Week 76 [Up to Week 100]

    16. Proportion of patients re-assigned and maintained on q12w up to Week 100 within the patients on q8w at Week 68 and on q12w at Week 80 [Up to Week 100]

    17. Proportion of patients with injections per planned dosing regimen (every 8, 12 or 16 weeks) [Up to Week 100]

      This outcome measure is pre-specified for brolucizumab treatment arm only

    18. Change from baseline in central subfield thickness (CSFT) at each assessment visit [Baseline up to Week 100]

      Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)

    19. Average change from baseline in CSFT over the period Week 40 through Week 52 / Week 88 through Week 100 [Baseline up to Week 100]

      Assessed by SD-OCT

    20. Average change from baseline in CSFT over the period Week 4 to Week 52 / 96 [Baseline up to Week 96]

      Assessed by SD-OCT

    21. Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit [Baseline up to Week 100]

      Assessed by SD-OCT

    22. Change from baseline in central subfield thickness-neurosensory (CSFTns) at each assessment visit [Baseline up to Week 100]

      Assessed by SD-OCT

    23. Average change from baseline in CSFTns over the period Week 40 through Week 52 / Week 88 through Week 100 [Baseline up to Week 100]

      Assessed by SD-OCT

    24. Average change from baseline in CSFTns over the period Week 4 to Week 52 / 100 [Baseline up to Week 100]

    25. Proportion of patients with presence of subretinal fluid (SRF) at each assessment visit [Baseline up to Week 100]

      Assessed by SD-OCT, angiography, and/or color fundus photography

    26. Proportion of patients with presence of intraretinal fluid (IRF) at each assessment visit [Baseline up to Week 100]

      Assessed by SD-OCT, angiography, and/or color fundus photography

    27. Proportion of patients with simultaneous absence of SRF and IRF at each assessment visit [Baseline up to Week 100]

      Assessed by SD-OCT, angiography, and/or color fundus photography

    28. Proportion of patients with presence of leakage on fluorescein angiography (FA) at Weeks 52 and 100 [Up to Week 100]

      Assessed by fluorescein angiography

    29. Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) score at each assessment visit [Baseline up to Week 100]

      The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative

    30. 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 [Baseline up to Week 100]

      ETDRS-DRSS

    31. Change from baseline in patient reported outcomes (VFQ-25) total and subscale scores up to Week 100 [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

    32. Systemic brolucizumab/aflibercept concentration [Up to Week 24]

      Blood draw

    33. Anti-Drug Antibody (ADA) status [Up to Week 100]

      Blood draw

    34. Average change from baseline in BCVA from the period Week 88 to 100 [Baseline up to Week 100]

      Assessed with ETDRS visual acuity testing charts

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 the 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Alken Belgium 3570
    2 Novartis Investigative Site Sofia Bulgaria 1606
    3 Novartis Investigative Site Sofia Bulgaria 1784
    4 Novartis Investigative Site Varna Bulgaria 9000
    5 Novartis Investigative Site Hradec Kralove CZE Czechia 500 05
    6 Novartis Investigative Site Praha 10 Czechia 100 34
    7 Novartis Investigative Site Praha Czechia 12808
    8 Novartis Investigative Site Aalborg Denmark 9000
    9 Novartis Investigative Site Roskilde Denmark 4000
    10 Novartis Investigative Site Tallinn Estonia 11412
    11 Novartis Investigative Site Tartu Estonia 51014
    12 Novartis Investigative Site Bobigny cedex Seine Saint Denis France 93009
    13 Novartis Investigative Site Bordeaux France 33000
    14 Novartis Investigative Site Creteil France 94000
    15 Novartis Investigative Site Dijon France 21034
    16 Novartis Investigative Site Lyon Cedex 04 France 69317
    17 Novartis Investigative Site Lyon France 69275
    18 Novartis Investigative Site Marseille France F 13008
    19 Novartis Investigative Site Montauban France 82000
    20 Novartis Investigative Site Nantes Cedex 1 France 44093
    21 Novartis Investigative Site Paris cedex 10 France 75010
    22 Novartis Investigative Site Paris France 75015
    23 Novartis Investigative Site Rouen France 76100
    24 Novartis Investigative Site Berlin Germany 10713
    25 Novartis Investigative Site Duesseldorf Germany 40212
    26 Novartis Investigative Site Freiburg Germany 79106
    27 Novartis Investigative Site Gottingen Germany 37075
    28 Novartis Investigative Site Leipzig Germany 04103
    29 Novartis Investigative Site Muenster Germany 48145
    30 Novartis Investigative Site Ulm Germany 89075
    31 Novartis Investigative Site Budapest Hungary 1083
    32 Novartis Investigative Site Debrecen Hungary 4012
    33 Novartis Investigative Site Nyiregyhaza Hungary H 4400
    34 Novartis Investigative Site Szeged Hungary H 6725
    35 Novartis Investigative Site Szombathely Hungary 9700
    36 Novartis Investigative Site Chennai Tamil Nadu India 600006
    37 Novartis Investigative Site Coimbatore Tamil Nadu India 641014
    38 Novartis Investigative Site Hyderabad Telangana India
    39 Novartis Investigative Site Chandigarh India 160012
    40 Novartis Investigative Site New Delhi India 110029
    41 Novartis Investigative Site Bundang Gu Gyeonggi Do Korea, Republic of 13620
    42 Novartis Investigative Site Busan Korea, Republic of 602739
    43 Novartis Investigative Site Seoul Korea, Republic of 02841
    44 Novartis Investigative Site Seoul Korea, Republic of 05505
    45 Novartis Investigative Site Seoul Korea, Republic of 06351
    46 Novartis Investigative Site Seoul Korea, Republic of 07301
    47 Novartis Investigative Site Riga Latvia LV 1002
    48 Novartis Investigative Site Ashrafieh Lebanon 166830
    49 Novartis Investigative Site Beirut Lebanon 116-5311
    50 Novartis Investigative Site Beirut Lebanon 70-933
    51 Novartis Investigative Site Kaunas LTU Lithuania LT 50161
    52 Novartis Investigative Site Vilnius Lithuania LT 08661
    53 Novartis Investigative Site Petaling Jaya Selangor Darul Ehsan Malaysia 46150
    54 Novartis Investigative Site Shah Alam Selangor Malaysia 40000
    55 Novartis Investigative Site Oslo Norway NO 0450
    56 Novartis Investigative Site Gdansk Poland 80 809
    57 Novartis Investigative Site Cheboksary Russian Federation 428028
    58 Novartis Investigative Site Ekaterinburg Russian Federation 620109
    59 Novartis Investigative Site Kazan Russian Federation 420066
    60 Novartis Investigative Site Moscow Russian Federation 119021
    61 Novartis Investigative Site Moscow Russian Federation 127486
    62 Novartis Investigative Site Singapore Singapore 168751
    63 Novartis Investigative Site Singapore Singapore S308433
    64 Novartis Investigative Site Banska Bystrica Slovakia 97517
    65 Novartis Investigative Site Bratislava Slovakia 82606
    66 Novartis Investigative Site Bratislava Slovakia 83301
    67 Novartis Investigative Site Poprad Slovakia 058 45
    68 Novartis Investigative Site Trencin Slovakia 91171
    69 Novartis Investigative Site Oerebro Sweden 701 85
    70 Novartis Investigative Site Bern Switzerland 3012
    71 Novartis Investigative Site Zuerich Switzerland 8063
    72 Novartis Investigative Site Changhua Taiwan 50006
    73 Novartis Investigative Site Taichung Taiwan 40447
    74 Novartis Investigative Site Taoyuan Taiwan 33305
    75 Novartis Investigative Site Ankara Turkey 06100
    76 Novartis Investigative Site Gaziantep Turkey 27310
    77 Novartis Investigative Site Izmir Turkey 35340
    78 Novartis Investigative Site Kocaeli Turkey 41380

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03481660
    Other Study ID Numbers:
    • CRTH258B2302
    • 2017-003960-11
    First Posted:
    Mar 29, 2018
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 2, 2022