Diabetic Macular EdemaPhase 3KINGFISHERNCT03917472
Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macular Edema, run by Novartis Pharmaceuticals at 92 sites in 5 countries.
Trial summary
The purpose of this study was to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to diabetic macular edema (DME). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Brolucizumab and Aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 517 participants
- Where
- 92 sitesin 5 countries
- Study dates
- 17 Jul 2019to 24 Mar 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent must be obtained prior to participation in the study.
- Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening.
- Study eye: Visual impairment due to DME with:
- Best-corrected visual acuity (BCVA) score between 73 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters
- DME involving the center of the macula, with Central Subfield Thickness (CSFT) ≥ 320 µm on Spectral Domain Optical Coherence Tomography (SD-OCT)
Who cannot join
- High-risk proliferative diabetic retinopathy (PDR) in the study eye
- Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention
- Any active intraocular or periocular infection or active intraocular inflammation in the either eye
- Uncontrolled glaucoma in the study eye
- Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200
- Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline
- Use of intraocular or periocular corticosteroids in the study eye during the 6-month period prior to baseline, and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline
- Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline
Trial locations and contacts
92 sites in 5 countries.
92 sites in 5 countries
United States74 sites
Novartis Investigative Site
‘Aiea, Hawaii, 96701
Novartis Investigative Site
Abilene, Texas, 79606
Novartis Investigative Site
Altamonte Springs, Florida, 32701
Novartis Investigative Site
Atlanta, Georgia, 30342
Novartis Investigative Site
Austin, Texas, 78705
Novartis Investigative Site
Austin, Texas, 78731
Novartis Investigative Site
Austin, Texas, 78750
Novartis Investigative Site
Bellaire, Texas, 77401
Novartis Investigative Site
Beverly Hills, California, 90211
Novartis Investigative Site
Bloomfield, New Jersey, 07003
Novartis Investigative Site
Bloomington, Illinois, 61704
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Campbell, California, 95008
Novartis Investigative Site
Chattanooga, Tennessee, 37421
Novartis Investigative Site
Cleveland, Ohio, 44122
Novartis Investigative Site
Columbus, Ohio, 43210
Novartis Investigative Site
Dallas, Texas, 75231
Novartis Investigative Site
Deerfield Beach, Florida, 33064
Novartis Investigative Site
Dublin, Ohio, 43016
Novartis Investigative Site
Eugene, Oregon, 97401
Novartis Investigative Site
Fort Lauderdale, Florida, 33309
Novartis Investigative Site
Fort Myers, Florida, 33912-7125
Novartis Investigative Site
Fort Worth, Texas, 76104
Novartis Investigative Site
Fresno, California, 93720
Novartis Investigative Site
Germantown, Tennessee, 38138
Novartis Investigative Site
Hagerstown, Maryland, 21740
Novartis Investigative Site
Harlingen, Texas, 78550
Novartis Investigative Site
Hickory, North Carolina, 28602
Novartis Investigative Site
Houston, Texas, 77025
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Huntington Beach, California, 92647
Novartis Investigative Site
Indianapolis, Indiana, 46280
Novartis Investigative Site
Kansas City, Missouri, 64133
Novartis Investigative Site
Kingston, Pennsylvania, 95403
Novartis Investigative Site
Leawood, Kansas, 66211
Novartis Investigative Site
Lenexa, Kansas, 66215
Novartis Investigative Site
Loma Linda, California, 92354
Novartis Investigative Site
Madison, Wisconsin, 53705-3611
Novartis Investigative Site
Marietta, Georgia, 30060
Novartis Investigative Site
Minneapolis, Minnesota, 55435
Novartis Investigative Site
Morgantown, West Virginia, 26506
Novartis Investigative Site
Mountain View, California, 94040
Novartis Investigative Site
New Albany, Indiana, 47150
Novartis Investigative Site
Norfolk, Virginia, 23502
Novartis Investigative Site
Oak Forest, Illinois, 60452
Novartis Investigative Site
Oakland, California, 94609
Novartis Investigative Site
Orlando, Florida, 32804
Novartis Investigative Site
Pasadena, California, 91107
Novartis Investigative Site
Phoenix, Arizona, 85016
Novartis Investigative Site
Phoenix, Arizona, 85053
Novartis Investigative Site
Pinellas Park, Florida, 33782
Novartis Investigative Site
Poway, California, 92064
Novartis Investigative Site
Rancho Cordova, California, 95670
Novartis Investigative Site
Redlands, California, 92374
Novartis Investigative Site
Reno, Nevada, 89502
Novartis Investigative Site
Riverside, California, 92505
Novartis Investigative Site
Rochester, New York, 14620
Novartis Investigative Site
Royal Oak, Michigan, 48073
Novartis Investigative Site
Sacramento, California, 95817
Novartis Investigative Site
Sacramento, California, 95841
Novartis Investigative Site
San Antonio, Texas, 78240
Novartis Investigative Site
San Francisco, California, 94107
Novartis Investigative Site
Santa Ana, California, 92705
Novartis Investigative Site
Santa Barbara, California, 93103
Novartis Investigative Site
Southern Pines, North Carolina, 28387
Novartis Investigative Site
Southlake, Texas, 76092
Novartis Investigative Site
Springfield, Illinois, 62704
Novartis Investigative Site
St. Petersburg, Florida, 33711
Novartis Investigative Site
Tampa, Florida, 33609
Novartis Investigative Site
Teaneck, New Jersey, 07666
Novartis Investigative Site
Torrance, California, 90509-2910
Novartis Investigative Site
Tucson, Arizona, 85704-5614
Novartis Investigative Site
Ventura, California, 93003
Novartis Investigative Site
West Des Moines, Iowa, 50266
Slovakia7 sites
Novartis Investigative Site
Banská Bystrica, 97517
Novartis Investigative Site
Bratislava, 82606
Novartis Investigative Site
Bratislava, 85107
Novartis Investigative Site
Poprad, 058 45
Novartis Investigative Site
Trebišov, 075 01
Novartis Investigative Site
Trenčín, 91171
Novartis Investigative Site
Zvolen, 960 01
Hungary5 sites
Novartis Investigative Site
Budapest, 1083
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Pécs, Baranya, 7621
Novartis Investigative Site
Szeged, H 6725
Novartis Investigative Site
Zalaegerszeg, Zala County, 8900
Israel5 sites
Novartis Investigative Site
Haifa, 3339419
Novartis Investigative Site
Haifa, 3436212
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 4941492
Novartis Investigative Site
Tel Aviv, 6789140
About this study
Official title: A 12-Month, 2-Arm, Randomized, Double-Masked, Multicenter Phase III Study Assessing the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KINGFISHER)
The purpose of this study was to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to diabetic macular edema (DME).
Read the detailed description
This study was designed as a Phase III, multi-center, randomized, double-masked, active controlled, parallel group prospective study to evaluate if brolucizumab 6 mg dosed q4w is safe and effective in the treatment of subjects with visual impairment due to diabetic macular edema (DME). Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 2:1 ratio to one of two treatment arms i.e., brolucizumab 6 mg and aflibercept 2 mg. Only one eye was selected as study eye and treated with study medication.
The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 48). For all subjects, the last study assessment was performed at the Week 52/end of study (EOS) visit. All subjects had study visits q4w through Week 52. The primary analysis was performed at the EOS visit (Week 52).
To ensure masking was maintained, the investigational site had both masked and unmasked staff to perform the masked and unmasked study assessments/procedures accordingly.
- Conditions
- Diabetic Macular Edema
- Being tested
- Brolucizumab, Aflibercept
- Keywords
- Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular edema (DME), macular edema, diabetic retinopathy
- Medical subject headings
- Macular Edema, Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrolucizumabDrug
Also called RTH258, ESBA1008
Intravitreal injection
AfliberceptDrug
Also called Eylea
Intravitreal injection
| Study group | Role | What they receive |
|---|---|---|
| Brolucizumab 6mg q4w | Experimental | Brolucizumab 6 mg/0.05 mL every 4 weeks. Receives: Drug: Brolucizumab |
| Aflibercept 2mg q4w | Active comparator | Aflibercept 2mg/0.05 mL every 4 weeks Receives: Drug: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Last observation carried forward (LOCF) was used for the imputation of missing values.
Measured: Baseline, Week 52
Secondary outcomes (14)
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit
Central Subfield Thickness assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit
Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with simultaneous absence of SRF and IRF in the study eye by visit. Events and censoring after 52 weeks are included in week 52 row.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Fluid status assessments after start of alternative DME treatment in the study eye are censored. Time to first fluid-free macula analysis is based on the subset of subjects with fluid present at baseline and at least one post-baseline assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Fluid status assessments after start of alternative DME treatment in the study eye are censored. Time to first fluid-free macula analysis is based on the subset of subjects with fluid present at baseline and at least one post-baseline assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. CSFT assessments after start of alternative DME treatment in the study eye are censored. Time to first absence of DME based on subjects with valid baseline and at least one post-baseline CSFT assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. CSFT assessments after start of alternative DME treatment in the study eye are censored. Time to first absence of DME based on subjects with valid baseline and at least one post-baseline CSFT assessment. Time (week) was calculated by (study day / 7). Events and censoring after 52 weeks were included in week 52 row.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Measured: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better functioning.
Measured: Baseline, Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye
The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative.
Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.
Subjects who had full/partial panretinal photocoagulation or local photocoagulation for new vessel (DRSS score 60) at any visit were excluded.
DRSS scores after start of alternative DME treatment in the study eye are censored and replaced by the last value prior to start of this alternative treatment.
Measured: Baseline, Weeks 12, 24 and 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye
The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative.
Severity of Diabetic retinopathy was evaluated using the ETDRS DRSS score assessed by the Central Reading Center based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on the original scale with scores varying from 10 (DR absent) to 85 (very advanced PDR). All DRSS values were then converted into a 12-level scale, allowing the derivation of the ≥2-step and ≥3-step change from baseline for each post-baseline assessment".
A lower score represents better functioning.
Subjects who had full/partial panretinal photocoagulation or local photocoagulation for new vessel (DRSS score 60) at any visit were excluded.
DRSS scores after start of alternative DME treatment in the study eye are censored and replaced by the last value prior to start of this alternative treatment.
Measured: Baseline, Weeks 12, 24 and 52
Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm
Measured: Baseline
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye
Measured: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.
Number of Subjects With Non-ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm)
Measured: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2019
- Study start17 Jul 2019
- Primary completion24 Mar 2021
- Study completion24 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03917472
- Sponsor's protocol ID
- CRTH258B2305
- Other IDs
- 2019-001004-37, 2019
- Acronym
- KINGFISHER
- Status last verified
- Aug 2022
- First submitted
- 11 Apr 2019
- Last updated
- 12 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 the patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to criteria and process described on www.clinicalstudydatarequest.com
Publications
Alhelaly M, Abbasgholizadeh R, Chung YC, Habibi A, Quarta A, Soylu C, Chujo S, Huang YC, He Y, Nittala MG, Sadda SR, Ip MS. Comparison of Retinal Nonperfusion in Diabetic Macular Edema Treated with Brolucizumab Versus Aflibercept: A KINGFISHER Trial Analysis. Am J Ophthalmol. 2026 Jul 23:S0002-9394(26)00419-8. doi: 10.1016/j.ajo.2026.07.041. Online ahead of print.
PubMed 42492647Singh RP, Barakat MR, Ip MS, Wykoff CC, Eichenbaum DA, Joshi S, Warrow D, Sheth VS, Stefanickova J, Kim YS, He F, Cho GE, Wang Y, Emanuelli A. Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial. JAMA Ophthalmol. 2023 Dec 1;141(12):1152-1160. doi: 10.1001/jamaophthalmol.2023.5248.
PubMed 37971723
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-Month, 2-Arm, Randomized, Double-Masked, Multicenter Phase III Study Assessing the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KINGFISHER)
- ClinicalTrials.gov ID
- NCT03917472
- Acronym / sponsor ID
- KINGFISHER / CRTH258B2305
- Conditions
- Diabetic Macular Edema
- Keywords
- Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular edema (DME), macular edema, diabetic retinopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 24 Mar 2021 (actual)
- Study completion
- 24 Mar 2021 (actual)
- First posted
- 17 Apr 2019 (actual)
- Results
- Posted 21 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to diabetic macular edema (DME).
Detailed description
This study was designed as a Phase III, multi-center, randomized, double-masked, active controlled, parallel group prospective study to evaluate if brolucizumab 6 mg dosed q4w is safe and effective in the treatment of subjects with visual impairment due to diabetic macular edema (DME). Subjects who met all the inclusion and none of the exclusion criteria were randomized in a 2:1 ratio to one of two treatment arms i.e., brolucizumab 6 mg and aflibercept 2 mg. Only one eye was selected as study eye and treated with study medication.
The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 48). For all subjects, the last study assessment was performed at the Week 52/end of study (EOS) visit. All subjects had study visits q4w through Week 52. The primary analysis was performed at the EOS visit (Week 52).
To ensure masking was maintained, the investigational site had both masked and unmasked staff to perform the masked and unmasked study assessments/procedures accordingly.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brolucizumab 6mg q4w | Experimental | Drug: BrolucizumabBrolucizumab 6 mg/0.05 mL every 4 weeks. |
| Aflibercept 2mg q4w | Active comparator | Drug: AfliberceptAflibercept 2mg/0.05 mL every 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening.
- Study eye: Visual impairment due to DME with:
Key exclusion criteria (8 listed)
- High-risk proliferative diabetic retinopathy (PDR) in the study eye
- Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention
- Any active intraocular or periocular infection or active intraocular inflammation in the either eye
- Uncontrolled glaucoma in the study eye
- Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrolucizumabAlso: RTH258, ESBA1008Intravitreal injection | Drug | Brolucizumab 6mg q4w |
| AfliberceptAlso: EyleaIntravitreal injection | Drug | Aflibercept 2mg q4w |
Primary outcome
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. Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/40 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.
14 secondary outcomes
Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Number and Percentage of Participants With Fluid-free Macula in the Study Eye at Each Post-baseline Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Number and Percentage of Participants With Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) at Each Post-baseline Visit for the Study Eye
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Number of Subjects With Absence of SRF / IRF and Number of Subjects Censored by Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Fluid-free Macula - Time-to-first Absence of Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) in the Study Eye - Kaplan-Meier Analysis - Probability of Absence of SRF/IRF by Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Number of Subjects With Probability of Absence of DME and Number Censored by Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Time to First Absence of Diabetic Macular Edema (DME) (CSFT < 280 μm) in the Study Eye at Each Post-baseline Visit - Kaplan-Meier Analysis - Probability of Absence of DME by Visit
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye
Time frame: Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and 52
Gain in Best-corrected Visual Acuity (BCVA) (Letters Read): Number (%) of Subjects Who Gained ≥ 5, 10, or 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters in the Study Eye at Week 52
Time frame: Baseline, Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye
Time frame: Baseline, Weeks 12, 24 and 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye
Time frame: Baseline, Weeks 12, 24 and 52
Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm
Time frame: Baseline
Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.
Number of Subjects With Non-ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm)
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 52 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42492647Alhelaly M, Abbasgholizadeh R, Chung YC, Habibi A, Quarta A, Soylu C, Chujo S, Huang YC, He Y, Nittala MG, Sadda SR, Ip MS. Comparison of Retinal Nonperfusion in Diabetic Macular Edema Treated with Brolucizumab Versus Aflibercept: A KINGFISHER Trial Analysis. Am J Ophthalmol. 2026 Jul 23:S0002-9394(26)00419-8. doi: 10.1016/j.ajo.2026.07.041. Online ahead of print.
- Derived from this study: PubMed 37971723Singh RP, Barakat MR, Ip MS, Wykoff CC, Eichenbaum DA, Joshi S, Warrow D, Sheth VS, Stefanickova J, Kim YS, He F, Cho GE, Wang Y, Emanuelli A. Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial. JAMA Ophthalmol. 2023 Dec 1;141(12):1152-1160. doi: 10.1001/jamaophthalmol.2023.5248.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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 the patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
92 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macular Edema, run by Novartis Pharmaceuticals at 92 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 92 sites in United States, Slovakia, Hungary, Israel, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 (time frame: Baseline, Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03917472, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2022.