Back to results

Efficacy and Safety of Brolucizumab vs Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KINGFISHER)

Primary Purpose

Diabetic Macular Edema

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Brolucizumab

Aflibercept

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular edema (DME), macular edema, diabetic retinopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Brolucizumab 6mg q4w

Aflibercept 2mg q4w

Arm Description

Brolucizumab 6 mg/0.05 mL every 4 weeks.

Aflibercept 2mg/0.05 mL every 4 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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 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.

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

Best Corrected Visual Acuity (Letters Read): Change From Baseline in Best-corrected Visual Acuity (BCVA) at Each Post-baseline Visit for the Study Eye

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

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.

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

Anti-Drug Antibody (ADA): Frequency Distribution of Pre-existing ADA Status in the Brolucizumab Arm

Ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term in the Study Eye

Number of Subjects With Non-ocular AEs (Greater Than or Equal to 2% in Any Treatment Arm)

Full Information

NCT ID

NCT03917472

First Posted

April 11, 2019

Last Updated

August 11, 2022

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03917472

Brief Title

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

Acronym

KINGFISHER

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

July 17, 2019 (Actual)

Primary Completion Date

March 24, 2021 (Actual)

Study Completion Date

March 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Macular Edema

Keywords

Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular edema (DME), macular edema, diabetic retinopathy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

A masked evaluating investigator will be responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator was to perform the injections and assess patient safety following the injections.

Allocation

Randomized

Enrollment

517 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Brolucizumab 6mg q4w

Arm Type

Experimental

Arm Description

Brolucizumab 6 mg/0.05 mL every 4 weeks.

Arm Title

Aflibercept 2mg q4w

Arm Type

Active Comparator

Arm Description

Aflibercept 2mg/0.05 mL every 4 weeks

Intervention Type

Drug

Intervention Name(s)

Brolucizumab

Other Intervention Name(s)

RTH258, ESBA1008

Intervention Description

Intravitreal injection

Intervention Type

Drug

Intervention Name(s)

Aflibercept

Other Intervention Name(s)

Eylea

Intervention Description

Intravitreal injection

Primary Outcome Measure Information:

Title

Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52

Description

Time Frame

Baseline, Week 52

Secondary Outcome Measure Information:

Title

Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit

Description

Central Subfield Thickness assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Time Frame