KITE: A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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.
- 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.
- Change from baseline in BCVA at each visit up to Week 100 [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 [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 [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 [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) [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 [Baseline up to Week 100]
Assessed with ETDRS visual acuity testing charts
- Absolute BCVA ≥73 ETDRS letters at each post-baseline visit [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) [Up to Week 64]
- 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
- 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
- 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
- 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]
- 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]
- 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
- 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)
- 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
- Average change from baseline in CSFT over the period Week 4 to Week 52 / 96 [Baseline up to Week 96]
Assessed by SD-OCT
- Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit [Baseline up to Week 100]
Assessed by SD-OCT
- Change from baseline in central subfield thickness-neurosensory (CSFTns) at each assessment visit [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 [Baseline up to Week 100]
Assessed by SD-OCT
- Average change from baseline in CSFTns over the period Week 4 to Week 52 / 100 [Baseline up to Week 100]
- 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
- 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
- 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
- Proportion of patients with presence of leakage on fluorescein angiography (FA) at Weeks 52 and 100 [Up to Week 100]
Assessed by fluorescein angiography
- 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
- 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
- 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
- Systemic brolucizumab/aflibercept concentration [Up to Week 24]
Blood draw
- Anti-Drug Antibody (ADA) status [Up to Week 100]
Blood draw
- 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
Inclusion Criteria:
-
Written informed consent before any assessment
-
Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
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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:
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Active proliferative diabetic retinopathy in the study eye
-
Active intraocular or periocular infection or active intraocular inflammation in the study eye
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Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
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Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
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Stroke or myocardial infarction during the 6-month period prior to baseline
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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 | |
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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.- CRTH258B2302
- 2017-003960-11