Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration

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: NCT04047472
Recruitment Status : Suspended (Only recruitment temporarily paused due to safety measures)
First Posted : August 6, 2019
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
To compare brolucizumab to aflibercept in Chinese patients with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)

Condition or disease Intervention/treatment Phase
Neovascular Age-Related Macular Degeneration Drug: Brolucizumab 6mg Drug: Aflibercept 2 mg Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 494 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Twelve-Month, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Comparing the Efficacy and Safety of Brolucizumab 6 mg Versus Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration
Actual Study Start Date : November 29, 2019
Estimated Primary Completion Date : June 26, 2023
Estimated Study Completion Date : June 26, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Brolucizumab 6 mg Drug: Brolucizumab 6mg
Subjects will receive Brolucizumab 3 x q4w up to Week 8 followed by q12w / q8w up to Week 40 or Week 44, depending on disease activity status.

Active Comparator: Aflibercept 2 mg Drug: Aflibercept 2 mg
Subjects will receive Aflibercept 3 x q4w up to Week 8 followed by q8w up to Week 40.




Primary Outcome Measures :
  1. Change in Best-Corrected Visual Acuity [ Time Frame: Baseline to Week 48 ]
    To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA

  2. Average change in Best-Corrected Visual Acuity [ Time Frame: Baseline, over the period Week 36 to Week 48 ]
    To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA


Secondary Outcome Measures :
  1. Proportion of subjects with treatment regimen of every 12 weeks in brolucizumab arm [ Time Frame: Baseline up to Week 48 ]
    To estimate the proportion of q12w subjects (1 injection every 12 weeks) up to Week 48 in the brolucizumab 6 mg treatment arm"

  2. Proportion of patients with treatment regimen of every 12 weeks (q12w) interval at Week 48 of those who do not need every 8 weeks treatment interval in brolucizumab arm [ Time Frame: Week 16, Week 20 and Week 48 ]
    To estimate the predictive value of the first regimen of every 12 weeks (q12w) cycle (at Week 16 and Week 20) for maintenance of q12w treatment regimen

  3. Change in Best Corrected Visual Acuity (BCVA) [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  4. Average change in Best-Corrected Visual Acuity [ Time Frame: Baseline, over the period of Week 4 to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  5. Average change in Best-Corrected Visual Acuity [ Time Frame: Baseline, over the period of Week 12 to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  6. Proportion of patients who gain in best-correct visual acuity of 15/10/5 letters or more [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  7. Percentage of subjects with Best-Corrected Visual Acuity of 73 letters or more at each visit [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  8. Proportion of subjects who loss in best-corrected visual acuity of 15/10/5 letters or more [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period

  9. Change in Central Subfield Thickness Total [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  10. Average change in Central Subfield Thickness Total [ Time Frame: Baseline, over the period of Week 36 to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  11. Average Change in Central Subfield Thickness Total [ Time Frame: Baseline, over the period of Week 4 to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  12. Change in Central Subfield Thickness-neurosensory retina [ Time Frame: From Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  13. Change in in area of choroidal neovascularization lesion [ Time Frame: Baseline, Weeks 12 and Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  14. Proportion of subjects who have presence of subretinal and/or intraretinal fluid (central subfield) [ Time Frame: Baseline up to Week 48, specifically at Week 16 and Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  15. Number of visits with simultaneous absence of subretinal and intraretinal fluid (central subfield) [ Time Frame: Over the period of Week 36 to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  16. Proportion of subjects who have presence of subretinal fluid (central subfield) [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  17. Proportion of subjects who have presence of intraretinal fluid (central subfield) [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  18. Proportion of subjects who presence of sub retinal pigment epithelium fluid (central subfield) [ Time Frame: Baseline up to Week 48 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters

  19. Change in Central Subfield Thickness Total [ Time Frame: Baseline up to week 16 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase

  20. Proportion of subjects who presence of subretinal and /or intraretinal fluid (central subfield) [ Time Frame: At Week 16 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase

  21. Proportion of subjects who need every 8 weeks injection [ Time Frame: At Week 16 ]
    To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase

  22. Change in subject reported outcomes (Visual Function Questionnaire-25) total and subscale scores [ Time Frame: Baseline up to Weeks 24 and Week 48 ]
    To assess visual function-related subject reported outcomes following treatment with brolucizumab 6 mg relative to aflibercept 2 mg. 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.

  23. Proportion of subjects who have positive anti-drug antibodies status [ Time Frame: At Baseline (enrollment), Weeks 4, 12, 24, 36, and 48 (End of Study) ]
    To assess immunogenicity of brolucizumab 6 mg

  24. Pharmacokinetic parameters: Cmax after first brolucizumab 6 mg dose in a subset of subjects [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 ]
    PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Cmax (maximum concentration) of brolucizumab at 6 mg following a single intravitreal injection

  25. Pharmacokinetic parameters: Tmax after first brolucizumab 6 mg dose in a subset of subjects [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 ]
    PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Tmax (time to maximum concenration) of brolucizumab at 6 mg following a single intravitreal injection

  26. Pharmacokinetic parameters: AUClast after first brolucizumab 6 mg dose in a subset of subjects [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 ]
    PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUClast (Area under the curve up to the last validated measurable plasma concentration) of brolucizumab at 6 mg following a single intravitreal injection

  27. Pharmacokinetic parameters: AUCinf after first brolucizumab 6 mg dose in a subset of subjects [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 ]
    PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUCinf (area under the curve total exposure) of brolucizumab at 6 mg following a single intravitreal injection

  28. Pharmacokinetic parameters: Thalf after first brolucizumab 6 mg dose in a subset of subjects [ Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 ]
    PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Thalf (time to elimination of half-life) of brolucizumab at 6 mg following a single intravitreal injection



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.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed.
  • Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye
  • Total area of CNV>50% of the total lesion area in the study eye at screening

Exclusion Criteria:

  • Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at Baseline.
  • Central subfield of the study eye affected by fibrosis or geographic atrophy
  • Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 mmHg
  • Previous treatment with any anti-VEGF drugs in the study eye.
  • Previous treatment with any approved or investigational drugs for neovascular AMD in the study eye.

Other protocol-specified inclusion or 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): NCT04047472


Locations
Layout table for location information
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 410015
Novartis Investigative Site
Shantou, Guangdong, China, 515041
China, Hubei
Novartis Investigative Site
Wuhan, Hubei, China, 430070
China, Tianjin
Novartis Investigative Site
Tianjin, Tianjin, China, 300020
Novartis Investigative Site
Tianjin, Tianjin, China, 300070
China
Novartis Investigative Site
Beijing, China, 100044
Novartis Investigative Site
Beijing, China, 100050
Novartis Investigative Site
Beijing, China, 100730
Novartis Investigative Site
Shanghai, China, 200080
Novartis Investigative Site
Shanghai, China
Sponsors and Collaborators
Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04047472    
Other Study ID Numbers: CRTH258A2307
First Posted: August 6, 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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases