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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04058067
Recruitment Status : Suspended (Only recruitment temporarily paused due to safety measures)
First Posted : August 15, 2019
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 268 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 : August 23, 2019
Estimated Primary Completion Date : April 22, 2022
Estimated Study Completion Date : May 5, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

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 Name: 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 Name: Eylea




Primary Outcome Measures :
  1. Change in best-corrected visual acuity (BCVA) [ Time Frame: Baseline to Week 52 ]
    To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome


Secondary Outcome Measures :
  1. Average change in BCVA [ Time Frame: Baseline, over period Week 40 to Week 52 ]
    To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome

  2. Proportion of patients maintained treatment regimen of every 12 weeks in brolucizumab arm [ Time Frame: Baseline up to Week 52 ]
    To estimate the proportion of patients treated at every 12 weeks (q12w) frequency with brolucizumab

  3. 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 [ Time Frame: Up to Week 52 ]
    To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab

  4. Change in BCVA [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period

  5. Average change in BCVA [ Time Frame: 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

  6. Proportion of patients who gain in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period

  7. Time to achieve gain of ≥5, ≥10 and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more) [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period

  8. Proportion of patients who loss in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period

  9. Proportion of patients who have absolute BCVA ≥73 ETDRS letters at each post-baseline visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period

  10. Proportion of patients need q8w treatment [ Time Frame: Week 32 ]
    To evaluate the efficacy related to dosing regimen of brolucizumab

  11. Proportion of patients with per planned dosing regimen (q8w or q12w) [ Time Frame: Week 52 ]
    To evaluate the efficacy related to dosing regimen

  12. Change in Central Subfield Thickness (CSFT) at each assessment visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

  13. Average change in CSFT [ Time Frame: 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

  14. Proportion of patient who have normal CSFT (<280 microns) at each assessment visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

  15. Change in Central Subfield Thickness-neurosensory retina (CSFTns) at each assessment visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

  16. Average change in CSFTns [ Time Frame: 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

  17. Proportion of patients with presence of subretinal fluid (SRF), Intraretinal fluid (IRF) and simultaneous absence of SRF and IRF at each assessment visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

  18. Proportion of patients with presence of leakage on fluorescein angiography (FA) [ Time Frame: Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters

  19. Change from baseline in ETDRS Diabetic Retinopathy Severity Scale score at each assessment visit [ Time Frame: Baseline up to Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status

  20. Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52 [ Time Frame: Week 52 ]
    To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status

  21. Change in patient reported outcomes (Visual Function Questionnaire-25) total and subscale scores [ Time Frame: 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.

  22. Systemic brolucizumab concentration [ Time Frame: 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.

  23. Proportion of patients who have positive anti-drug antibody status in brolucizumab arm [ Time Frame: At Screening, Week 4, 12, 24, 36, and 52 (End of Study) ]
    To assess the immunogenicity of brolucizumab



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04058067


Locations
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China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510060
Novartis Investigative Site
Shantou, Guangdong, China, 515041
China, Hubei
Novartis Investigative Site
Wuhan, Hubei, China, 430070
China, Jiangsu
Novartis Investigative Site
Nanjing, Jiangsu, China, 210029
Novartis Investigative Site
Wuxi, Jiangsu, China
China, Sichuan
Novartis Investigative Site
Chengdu, Sichuan, China, 610041
China, Tianjin
Novartis Investigative Site
Tianjin, Tianjin, China, 300020
Novartis Investigative Site
Tianjin, Tianjin, China, 300070
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310014
China
Novartis Investigative Site
Beijing, China, 100034
Novartis Investigative Site
Beijing, China, 100730
Novartis Investigative Site
Chongqing, China, 400038
Novartis Investigative Site
Chongqing, China, 400042
Novartis Investigative Site
Shanghai, China, 200080
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04058067    
Other Study ID Numbers: CRTH258B2304
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: April 27, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Diabetic Macular Edema
Intravitreal injection
brolucizumab
aflibercept
Additional relevant MeSH terms:
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Vision Disorders
Vision, Low
Macular Edema
Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases