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NCT03481660: KITE

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

Completed Phase 3 Results posted Last updated 7 January 2025
What this trial tests

Phase 3 trial testing Brolucizumab in Diabetic Macular Edema in 360 participants. Completed in 8 June 2021.

Timeline
27 July 2018
Primary endpoint
29 June 2020
8 June 2021

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment360
Start date27 July 2018
Primary completion29 June 2020
Estimated completion8 June 2021
Sites78 locations across Malaysia, Taiwan, Poland, South Korea, Lebanon, Denmark, Russia, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Diabetic Macular Edema. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye Primary · Baseline, Week 52

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative di

GroupValue95% CI
Brolucizumab 6 mg10.69.3 – 11.9
Aflibercept 2 mg9.48.1 – 10.7
Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye Secondary · Baseline, period Week 40 through Week 52

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defin

GroupValue95% CI
Brolucizumab 6 mg10.39.1 – 11.5
Aflibercept 2 mg9.48.2 – 10.6
(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100. Secondary · Week 52, Week 100

The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen \[every 12 weeks (q12w)\].

Week 48
GroupValue95% CI
Brolucizumab 6 mg50.342.5 – 57.7
Week 96
GroupValue95% CI
Brolucizumab 6 mg36.829.1 – 45.5
(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36 Secondary · Week 36, Week 52

The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen \[every 12 weeks (q12w)\].

GroupValue95% CI
Brolucizumab 6 mg95.187.4 – 98.1
(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36 Secondary · Week 36, Week 100

Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension. The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier

GroupValue95% CI
Brolucizumab 6 mg69.657.4 – 78.9
(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76 Secondary · Week 68, Week 76, Week 100

Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension. The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier

GroupValue95% CI
Brolucizumab 6 mg87.973.3 – 94.8
(Brolucizumab Treatment Arm Only): Percentage of Participants Re-assigned and Maintained on q12w up to Week 100 Within the Patients on q8w at Week 68 and on q12w at Week 80 Secondary · Week 68, Week 80, Week 100

Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension. The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier

GroupValue95% CI
Brolucizumab 6 mg73.154.5 – 85.0
(Brolucizumab Treatment Arm Only): Number of Participants With Injections Per Planned Dosing Regimen (Every 8, 12 or 16 Weeks) Secondary · Week 100

Reported categorically for the subjects who completed the study treatment period: every 8 weeks (q8w), Every 12 weeks (q12w), Every 16 weeks (q16w)

GroupValue95% CI
Brolucizumab 6 mg74
Brolucizumab 6 mg32
Brolucizumab 6 mg35
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Each Visit up to Week 100 for the Study Eye Secondary · Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to st

Week 4
GroupValue95% CI
Brolucizumab 6 mg5.14.3 – 6.0
Aflibercept 2 mg4.23.4 – 5.1
Week 6
GroupValue95% CI
Brolucizumab 6 mg6.85.9 – 7.6
Aflibercept 2 mg5.95.0 – 6.7
Week 8
GroupValue95% CI
Brolucizumab 6 mg7.86.9 – 8.7
Aflibercept 2 mg6.75.8 – 7.5
Week 12
GroupValue95% CI
Brolucizumab 6 mg8.67.6 – 9.5
Aflibercept 2 mg7.76.7 – 8.6
Week 16
GroupValue95% CI
Brolucizumab 6 mg9.07.9 – 10.1
Aflibercept 2 mg8.37.2 – 9.5
Week 18
GroupValue95% CI
Brolucizumab 6 mg9.28.0 – 10.3
Aflibercept 2 mg9.28.0 – 10.3
Week 20
GroupValue95% CI
Brolucizumab 6 mg9.68.4 – 10.8
Aflibercept 2 mg9.48.2 – 10.6
Week 24
GroupValue95% CI
Brolucizumab 6 mg10.08.8 – 11.2
Aflibercept 2 mg8.77.5 – 9.9
Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 4 to Week 52/100 for the Study Eye Secondary · Baseline, period Week 4 through Week 52, period Week 4 through Week 100

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defin

period Week 4 through Week 52
GroupValue95% CI
Brolucizumab 6 mg9.18.2 – 10.1
Aflibercept 2 mg8.47.4 – 9.3
period Week 4 through Week 100
GroupValue95% CI
Brolucizumab 6 mg9.88.8 – 10.9
Aflibercept 2 mg8.77.7 – 9.8
Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 20 to Week 52/100 and Week 28 to Week 52/100 for the Study Eye Secondary · Baseline, period Week 20 through Week 52, period Week 20 through Week 100, period Week 28 through Week 52, period Week 28 through Week 100

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defin

period Week 20 through Week 52
GroupValue95% CI
Brolucizumab 6 mg10.18.9 – 11.2
Aflibercept 2 mg9.38.1 – 10.4
period Week 20 through Week 100
GroupValue95% CI
Brolucizumab 6 mg10.49.2 – 11.7
Aflibercept 2 mg9.28.0 – 10.4
period Week 28 through Week 52
GroupValue95% CI
Brolucizumab 6 mg10.19.0 – 11.3
Aflibercept 2 mg9.48.2 – 10.5
period Week 28 through Week 100
GroupValue95% CI
Brolucizumab 6 mg10.59.3 – 11.7
Aflibercept 2 mg9.28.0 – 10.5
Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 88 to 100 for the Study Eye Secondary · Baseline, period Week 88 through Week 100

Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defin

GroupValue95% CI
Brolucizumab 6 mg10.89.2 – 12.3
Aflibercept 2 mg8.77.1 – 10.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study treatment up to 30 days after last dose (maximum 35 months). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Brolucizumab 6mg
Serious: 53/179 (30%)
Deaths: 13/179
Aflibercept 2mg
Serious: 60/181 (33%)
Deaths: 9/181
Overall
Serious: 113/360 (31%)
Deaths: 22/360

Serious adverse events (134 terms)

ReactionSystemBrolucizumab 6mgAflibercept 2mgOverall
COVID-19Infections and infestations
PneumoniaInfections and infestations
Cardiac failureCardiac disorders
GangreneInfections and infestations
Cerebrovascular accidentNervous system disorders
Coronary artery diseaseCardiac disorders
Coronary artery stenosisCardiac disorders
Myocardial infarctionCardiac disorders
DeathGeneral disorders
Endophthalmitis - Study eyeInfections and infestations
Chronic kidney diseaseRenal and urinary disorders
Diabetic nephropathyRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiopulmonary failureCardiac disorders
Uveitis - Study eyeEye disorders
Vitreous haemorrhage - Fellow eyeEye disorders
DiarrhoeaGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
ErysipelasInfections and infestations
Other adverse events (68 terms — click to expand)

ReactionSystemBrolucizumab 6mgAflibercept 2mgOverall
Diabetic retinal oedema - Fellow eyeEye disorders
NasopharyngitisInfections and infestations
HypertensionVascular disorders
Cataract - Study eyeEye disorders
Cataract - Fellow eyeEye disorders
ProteinuriaRenal and urinary disorders
Dry eye - Study eyeEye disorders
AnaemiaBlood and lymphatic system disorders
Dry eye - Fellow eyeEye disorders
Conjunctival haemorrhage - Study eyeEye disorders
CoughRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Visual acuity reduced - Study eyeEye disorders
BronchitisInfections and infestations
Glycosylated haemoglobin increasedInvestigations
HeadacheNervous system disorders
Diabetic nephropathyRenal and urinary disorders
Vitreous haemorrhage - Fellow eyeEye disorders
InfluenzaInfections and infestations
Conjunctival haemorrhage - Fellow eyeEye disorders
Eye pain - Study eyeEye disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
Blood creatinine increasedInvestigations
Intraocular pressure increased - Study eyeInvestigations
HyperlipidaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
Blood pressure increasedInvestigations
Protein urine presentInvestigations
Back painMusculoskeletal and connective tissue disorders
Macular oedema - Fellow eyeEye disorders
Vitreous floaters - Study eyeEye disorders
Upper respiratory tract infectionInfections and infestations
Blood triglycerides increasedInvestigations
GoutMetabolism and nutrition disorders
Chronic kidney diseaseRenal and urinary disorders
Blepharitis - Fellow eyeEye disorders
Visual acuity reduced - Fellow eyeEye disorders

Most-reported serious reactions: COVID-19, Pneumonia, Cardiac failure, Gangrene, Cerebrovascular accident, Coronary artery disease, Coronary artery stenosis, Myocardial infarction.

Data from ClinicalTrials.gov NCT03481660 adverse events section.

Sponsor's own description

This was a Phase III, randomized, double-masked, multi-center, active-controlled, two-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with visual impairment due to diabetic macular edema (DME).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pathophysiology of Diabetic Retinopathy: The Old and the New.
    Kusuhara S, Fukushima Y, Ogura S, Inoue N, et al · · 2018 · cited 155× · PMID 30362302 · DOI 10.4093/dmj.2018.0182
  2. Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?
    Uludag G, Hassan M, Matsumiya W, Pham BH, et al · · 2022 · cited 60× · PMID 35818801 · DOI 10.1080/14712598.2022.2100694
  3. An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma.
    Ghanchi F, Bourne R, Downes SM, Gale R, et al · · 2022 · cited 35× · PMID 34974541 · DOI 10.1038/s41433-021-01766-w
  4. Emerging Insights and Interventions for Diabetic Retinopathy.
    Honasoge A, Nudleman E, Smith M, Rajagopal R. · · 2019 · cited 32× · PMID 31506830 · DOI 10.1007/s11892-019-1218-2
  5. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.
    Virgili G, Curran K, Lucenteforte E, Peto T, et al · · 2023 · cited 21× · PMID 38275741 · DOI 10.1002/14651858.cd007419.pub7
  6. Clinically Meaningful Change Estimates for the National Eye Institute Visual Function Questionnaire-25 in Patients With Diabetic Macular Edema.
    Bressler N, Haskova Z, Kapre A, Gentile B. · · 2024 · cited 2× · PMID 39680390 · DOI 10.1167/tvst.13.12.27
  7. Sustained Disease Control in DME Patients upon Treatment Cessation with Brolucizumab.
    Garweg JG, Steinhauer S. · · 2024 · cited 2× · PMID 38541760 · DOI 10.3390/jcm13061534

Verify or expand the search:

Other trials of Brolucizumab

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Trials by the same sponsor.

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