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

Primary Purpose

Diabetic Macular Edema

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Brolucizumab
Aflibercept
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring Diabetic Macular Edema, Intravitreal injection, brolucizumab, aflibercept

Eligibility Criteria

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

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Brolucizumab 6 mg

Aflibercept 2 mg

Arm Description

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

5 x every 4 weeks loading then every 8 weeks maintenance

Outcomes

Primary Outcome Measures

Change in best-corrected visual acuity (BCVA)
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome

Secondary Outcome Measures

Average change in BCVA
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome
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
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
Change in BCVA
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Average change in BCVA
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
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
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
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
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
Proportion of patients need q8w treatment
To evaluate the efficacy related to dosing regimen of brolucizumab
Proportion of patients with per planned dosing regimen (q8w or q12w)
To evaluate the efficacy related to dosing regimen
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
Average change in CSFT
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
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
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
Average change in CSFTns
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
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
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
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
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
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.
Systemic brolucizumab concentration
To confirm the systemic brolucizumab exposure in a subset of patients.
Proportion of patients who have positive anti-drug antibody status in brolucizumab arm
To assess the immunogenicity of brolucizumab

Full Information

First Posted
August 14, 2019
Last Updated
June 9, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04058067
Brief Title
To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema
Acronym
KINGLET
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
August 23, 2019 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
January 31, 2023 (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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
263 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brolucizumab 6 mg
Arm Type
Experimental
Arm Description
5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
Arm Title
Aflibercept 2 mg
Arm Type
Active Comparator
Arm Description
5 x every 4 weeks loading then every 8 weeks maintenance
Intervention Type
Drug
Intervention Name(s)
Brolucizumab
Other Intervention Name(s)
RTH258
Intervention Description
5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Other Intervention Name(s)
Eylea
Intervention Description
5 x every 4 weeks loading then every 8 weeks maintenance
Primary Outcome Measure Information:
Title
Change in best-corrected visual acuity (BCVA)
Description
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome
Time Frame
Baseline to Week 52
Secondary Outcome Measure Information:
Title
Average change in BCVA
Description
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome
Time Frame
Baseline, over period Week 40 to Week 52
Title
Proportion of patients maintained treatment regimen of every 12 weeks in brolucizumab arm
Description
To estimate the proportion of patients treated at every 12 weeks (q12w) frequency with brolucizumab
Time Frame
Baseline up to Week 52
Title
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
Description
To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab
Time Frame
Up to Week 52
Title
Change in BCVA
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52
Title
Average change in BCVA
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52, over period Week 20 to Week 52, Period Week 28 to Week 52
Title
Proportion of patients who gain in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52
Title
Time to achieve gain of ≥5, ≥10 and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more)
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52
Title
Proportion of patients who loss in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52
Title
Proportion of patients who have absolute BCVA ≥73 ETDRS letters at each post-baseline visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Time Frame
Baseline up to Week 52
Title
Proportion of patients need q8w treatment
Description
To evaluate the efficacy related to dosing regimen of brolucizumab
Time Frame
Week 32
Title
Proportion of patients with per planned dosing regimen (q8w or q12w)
Description
To evaluate the efficacy related to dosing regimen
Time Frame
Week 52
Title
Change in Central Subfield Thickness (CSFT) at each assessment visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline up to Week 52
Title
Average change in CSFT
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline, over period of Week 4 to Week 52, over period of Week 40 to Week 52
Title
Proportion of patient who have normal CSFT (<280 microns) at each assessment visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline up to Week 52
Title
Change in Central Subfield Thickness-neurosensory retina (CSFTns) at each assessment visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline up to Week 52
Title
Average change in CSFTns
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline, over the period of Week 4 to Week 52, over period of Week 40 to Week 52
Title
Proportion of patients with presence of subretinal fluid (SRF), Intraretinal fluid (IRF) and simultaneous absence of SRF and IRF at each assessment visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Baseline up to Week 52
Title
Proportion of patients with presence of leakage on fluorescein angiography (FA)
Description
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Time Frame
Week 52
Title
Change from baseline in ETDRS Diabetic Retinopathy Severity Scale score at each assessment visit
Description
To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status
Time Frame
Baseline up to Week 52
Title
Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52
Description
To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status
Time Frame
Week 52
Title
Change in patient reported outcomes (Visual Function Questionnaire-25) total and subscale scores
Description
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.
Time Frame
Baseline up to Week 28 and Week 52
Title
Systemic brolucizumab concentration
Description
To confirm the systemic brolucizumab exposure in a subset of patients.
Time Frame
Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment
Title
Proportion of patients who have positive anti-drug antibody status in brolucizumab arm
Description
To assess the immunogenicity of brolucizumab
Time Frame
At Screening, Week 4, 12, 24, 36, and 52 (End of Study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Novartis Investigative Site
City
Shantou
State/Province
Guangdong
ZIP/Postal Code
515041
Country
China
Facility Name
Novartis Investigative Site
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150001
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430070
Country
China
Facility Name
Novartis Investigative Site
City
Wuxi
State/Province
Jiangsu
ZIP/Postal Code
214002
Country
China
Facility Name
Novartis Investigative Site
City
Changchun City
State/Province
Jilin
ZIP/Postal Code
130041
Country
China
Facility Name
Novartis Investigative Site
City
Qingdao
State/Province
Shandong
ZIP/Postal Code
2666000
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300070
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
Facility Name
Novartis Investigative Site
City
Wenzhou
State/Province
Zhejiang
ZIP/Postal Code
325027
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400038
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400042
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
ZIP/Postal Code
210036
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200031
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200080
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200092
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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