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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04058067

Collaborator

(none)

263

Enrollment

Locations

Arms

41.1

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Brolucizumab Drug: Aflibercept	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

263 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 23, 2019

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Jan 26, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in best-corrected visual acuity (BCVA) [Baseline to Week 52]
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome

Secondary Outcome Measures

Average change in BCVA [Baseline, over period Week 40 to Week 52]
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 [Baseline up to Week 52]
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 [Up to Week 52]
To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab
Change in BCVA [Baseline up to Week 52]
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Average change in BCVA [Baseline up to Week 52, over period Week 20 to Week 52, Period Week 28 to Week 52]
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 [Baseline up to Week 52]
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) [Baseline up to Week 52]
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 [Baseline up to Week 52]
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 [Baseline up to Week 52]
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period
Proportion of patients need q8w treatment [Week 32]
To evaluate the efficacy related to dosing regimen of brolucizumab
Proportion of patients with per planned dosing regimen (q8w or q12w) [Week 52]
To evaluate the efficacy related to dosing regimen
Change in Central Subfield Thickness (CSFT) at each assessment visit [Baseline up to Week 52]
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Average change in CSFT [Baseline, over period of Week 4 to Week 52, over period of Week 40 to Week 52]
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 [Baseline up to Week 52]
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 [Baseline up to Week 52]
To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters
Average change in CSFTns [Baseline, over the period of Week 4 to Week 52, over period of Week 40 to Week 52]
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 [Baseline up to Week 52]
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) [Week 52]
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 [Baseline up to Week 52]
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 [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 [Baseline up to Week 28 and Week 52]
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 [Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment]
To confirm the systemic brolucizumab exposure in a subset of patients.
Proportion of patients who have positive anti-drug antibody status in brolucizumab arm [At Screening, Week 4, 12, 24, 36, and 52 (End of Study)]
To assess the immunogenicity of brolucizumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Guangzhou	Guangdong	China	510060
2	Novartis Investigative Site	Shantou	Guangdong	China	515041
3	Novartis Investigative Site	Harbin	Heilongjiang	China	150001
4	Novartis Investigative Site	Wuhan	Hubei	China	430070
5	Novartis Investigative Site	Wuxi	Jiangsu	China	214002
6	Novartis Investigative Site	Changchun City	Jilin	China	130041
7	Novartis Investigative Site	Qingdao	Shandong	China	2666000
8	Novartis Investigative Site	Chengdu	Sichuan	China	610041
9	Novartis Investigative Site	Tianjin	Tianjin	China	300020
10	Novartis Investigative Site	Tianjin	Tianjin	China	300070
11	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
12	Novartis Investigative Site	Hangzhou	Zhejiang	China	310009
13	Novartis Investigative Site	Hangzhou	Zhejiang	China	310014
14	Novartis Investigative Site	Wenzhou	Zhejiang	China	325027
15	Novartis Investigative Site	Beijing		China	100034
16	Novartis Investigative Site	Beijing		China	100044
17	Novartis Investigative Site	Beijing		China	100191
18	Novartis Investigative Site	Beijing		China	100730
19	Novartis Investigative Site	Chongqing		China	400038
20	Novartis Investigative Site	Chongqing		China	400042
21	Novartis Investigative Site	Nanjing		China	210036
22	Novartis Investigative Site	Shanghai		China	200031
23	Novartis Investigative Site	Shanghai		China	200080
24	Novartis Investigative Site	Shanghai		China	200092