To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema (KINGLET)

Novartis

Status and phase: Completed; Phase 3

Conditions: Diabetic Macular Edema

Treatments: Drug: Brolucizumab; Drug: Aflibercept

Study type: Interventional

Funder types: Industry

Identifiers

NCT04058067

CRTH258B2304

Details and patient eligibility

About

The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of Chinese patients with visual impairment due to Diabetic Macular Edema.

Full description

The study is a randomized, double-masked, multi-center, active-controlled, 2-arm study in Chinese patients with Diabetic macular edema (DME). Approximately 335 Chinese patients were planned to be screened (20% screening failure rate expected) and approximately 268 (134 per arm) patients were planned to be randomized in approximately 25 centers.

Patients who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of two treatment arms:

• Brolucizumab 6 mg: 5 × every 6 weeks (q6w) loading then every 12 weeks (q12w) or every 8 weeks (q8w) maintenance
• Aflibercept 2 mg: 5 × every 4 weeks (q4w) loading then q8w maintenance

Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Weeks 32, 36, and 48. In the brolucizumab arm, subjects who qualified for q12w during this initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at the subsequent DAA visit at Week 48, in which case subjects were switched to a q8w treatment interval until Week 52.

Enrollment: 266 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed informed consent must be obtained prior to participation in the study.

2. Patients ≥18 years of age at screening

3. Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) of ≤10% at screening

4. Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain as stable as medically acceptable during the course of the study

5. Study Eye Visual impairment due to diabetic macular edema (DME) with:

   • Best-corrected visual acuity (BCVA) score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing charts at a starting testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320) at screening and baseline
   • DME involving the center of the macula, with central subfield retinal thickness (e.g. measured from retinal pigment epithelium (RPE) to the inner limiting membrane (ILM) inclusively) of ≥320 μm on Spectral domain optical coherence tomography (SD-OCT) at screening.

Exclusion criteria

• Active Proliferative diabetic retinopathy (PDR) in the study eye as per investigator
• Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention for the duration of the study (e.g. cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) of any cause)
• Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
• Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema (ME), including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to investigator's judgment at Screening or Baseline
• Neovascularization of the iris in the study eye at screening or baseline
• Evidence of vitreomacular traction in the study eye at screening or baseline which in the opinion of the investigator, affects visual acuity
• Previous treatment with any anti-vascular growth factor (VEGF) drug or investigational drugs in the study eye

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

266 participants in 2 patient groups

Brolucizumab 6 mg

Experimental group

Description:

5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance

Treatment:

Drug: Brolucizumab

Aflibercept 2 mg

Active Comparator group

Description:

5 x every 4 weeks loading then every 8 weeks maintenance

Treatment:

Drug: Aflibercept