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

Novartis

Status and phase: Completed; Phase 3

Conditions: Diabetic Macular Edema

Treatments: Drug: Aflibercept; Drug: Brolucizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03917472

2019-001004-37 (EudraCT Number)

CRTH258B2305

Details and patient eligibility

About

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).

Full 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.

Enrollment: 517 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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517 participants in 2 patient groups

Brolucizumab 6mg q4w

Experimental group

Description:

Brolucizumab 6 mg/0.05 mL every 4 weeks.

Treatment:

Drug: Brolucizumab

Aflibercept 2mg q4w

Active Comparator group

Description:

Aflibercept 2mg/0.05 mL every 4 weeks

Treatment:

Drug: Aflibercept