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

A One-Year, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Chinese Patients With Visual Impairment Due to Diabetic Macular Edema

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

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Brolucizumab; Drug: Aflibercept

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Beijing, China, 100191
    • Novartis Investigative Site
  • Chongqing, China, 400038
    • Novartis Investigative Site
  • Chongqing, China, 400042
    • Novartis Investigative Site
  • Nanjing, China, 210036
    • Novartis Investigative Site
  • Shanghai, China, 200031
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Shanghai, China, 200092
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Novartis Investigative Site
    • Shantou, Guangdong, China, 515041
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430070
      • Novartis Investigative Site
  • Jiangsu
    • Wuxi, Jiangsu, China, 214002
      • Novartis Investigative Site
  • Jilin
    • Changchun City, Jilin, China, 130041
      • Novartis Investigative Site
  • Shandong
    • Qingdao, Shandong, China, 2666000
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
    • Tianjin, Tianjin, China, 300070
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310014
      • Novartis Investigative Site
    • Wenzhou, Zhejiang, China, 325027
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with type 1 or type 2 diabetes mellitus
• Visual impairment due to Diabetic Macular Edema

Exclusion Criteria:

• Any active intraocular or periocular infection or active intraocular inflammation
• Structural damage of the fovea
• Uncontrolled glaucoma
• Neovascularization of the iris

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 6 mg; 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Drug: Brolucizumab; 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance; Other Names: RTH258
Active Comparator: Aflibercept 2 mg; 5 x every 4 weeks loading then every 8 weeks maintenance	Drug: Aflibercept; 5 x every 4 weeks loading then every 8 weeks maintenance; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in best-corrected visual acuity (BCVA)	To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in BCVA	To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome	Baseline, over period Week 40 to Week 52
Proportion of patients maintained treatment regimen of every 12 weeks in brolucizumab arm	To estimate the proportion of patients treated at every 12 weeks (q12w) frequency with brolucizumab	Baseline up to Week 52
Proportion of patients maintained dosing regimen of every 12 weeks (q12w) interval up to Week 52, within those patients that qualified for q12w at dosing regimen at Week 36	To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab	Up to Week 52
Change in BCVA	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52
Average change in BCVA	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52, over period Week 20 to Week 52, Period Week 28 to Week 52
Proportion of patients who gain in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52
Time to achieve gain of ≥5, ≥10 and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more)	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52
Proportion of patients who loss in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52
Proportion of patients who have absolute BCVA ≥73 ETDRS letters at each post-baseline visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period	Baseline up to Week 52
Proportion of patients need q8w treatment	To evaluate the efficacy related to dosing regimen of brolucizumab	Week 32
Proportion of patients with per planned dosing regimen (q8w or q12w)	To evaluate the efficacy related to dosing regimen	Week 52
Change in Central Subfield Thickness (CSFT) at each assessment visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline up to Week 52
Average change in CSFT	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline, over period of Week 4 to Week 52, over period of Week 40 to Week 52
Proportion of patient who have normal CSFT (<280 microns) at each assessment visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline up to Week 52
Change in Central Subfield Thickness-neurosensory retina (CSFTns) at each assessment visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline up to Week 52
Average change in CSFTns	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline, over the period of Week 4 to Week 52, over period of Week 40 to Week 52
Proportion of patients with presence of subretinal fluid (SRF), Intraretinal fluid (IRF) and simultaneous absence of SRF and IRF at each assessment visit	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline up to Week 52
Proportion of patients with presence of leakage on fluorescein angiography (FA)	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Week 52
Change from baseline in ETDRS Diabetic Retinopathy Severity Scale score at each assessment visit	To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status	Baseline up to Week 52
Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52	To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status	Week 52
Change in patient reported outcomes (Visual Function Questionnaire-25) total and subscale scores	To assess visual function-related patient reported outcomes (VFQ-25) following treatment with brolucizumab relative to aflibercept. The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score will be calculated by averaging vision-targeted subscale scores, excluding the general health rating question.	Baseline up to Week 28 and Week 52
Systemic brolucizumab concentration	To confirm the systemic brolucizumab exposure in a subset of patients.	Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment
Proportion of patients who have positive anti-drug antibody status in brolucizumab arm	To assess the immunogenicity of brolucizumab	At Screening, Week 4, 12, 24, 36, and 52 (End of Study)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Diabetic Macular Edema; aflibercept; Intravitreal injection; brolucizumab
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Sensation Disorders; Macular Edema; Edema; Vision, Low; Vision Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: CRTH258B2304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No