Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration
Study Details
Study Description
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 |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Change in Best-Corrected Visual Acuity [Baseline to Week 48]
To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA
- Average change in Best-Corrected Visual Acuity [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
- Proportion of subjects with treatment regimen of every 12 weeks in brolucizumab arm [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"
- 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 [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
- Change in Best Corrected Visual Acuity (BCVA) [Baseline up to Week 48]
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
- Average change in Best-Corrected Visual Acuity [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
- Average change in Best-Corrected Visual Acuity [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
- Proportion of patients who gain in best-correct visual acuity of 15/10/5 letters or more [Baseline up to Week 48]
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
- Percentage of subjects with Best-Corrected Visual Acuity of 73 letters or more at each visit [Baseline up to Week 48]
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
- Proportion of subjects who loss in best-corrected visual acuity of 15/10/5 letters or more [Baseline up to Week 48]
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
- Change in Central Subfield Thickness Total [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
- Average change in Central Subfield Thickness Total [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
- Average Change in Central Subfield Thickness Total [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
- Change in Central Subfield Thickness-neurosensory retina [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
- Change in in area of choroidal neovascularization lesion [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
- Proportion of subjects who have presence of subretinal and/or intraretinal fluid (central subfield) [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
- Number of visits with simultaneous absence of subretinal and intraretinal fluid (central subfield) [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
- Proportion of subjects who have presence of subretinal fluid (central subfield) [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
- Proportion of subjects who have presence of intraretinal fluid (central subfield) [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
- Proportion of subjects who presence of sub retinal pigment epithelium fluid (central subfield) [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
- Change in Central Subfield Thickness Total [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
- Proportion of subjects who presence of subretinal and /or intraretinal fluid (central subfield) [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
- Proportion of subjects who need every 8 weeks injection [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
- Change in subject reported outcomes (Visual Function Questionnaire-25) total and subscale scores [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.
- Proportion of subjects who have positive anti-drug antibodies status [At Baseline (enrollment), Weeks 4, 12, 24, 36, and 48 (End of Study)]
To assess immunogenicity of brolucizumab 6 mg
- Pharmacokinetic parameters: Cmax after first brolucizumab 6 mg dose in a subset of subjects [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
- Pharmacokinetic parameters: Tmax after first brolucizumab 6 mg dose in a subset of subjects [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
- Pharmacokinetic parameters: AUClast after first brolucizumab 6 mg dose in a subset of subjects [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
- Pharmacokinetic parameters: AUCinf after first brolucizumab 6 mg dose in a subset of subjects [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
- Pharmacokinetic parameters: Thalf after first brolucizumab 6 mg dose in a subset of subjects [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
Eligibility Criteria
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
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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
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Guangzhou | Guangdong | China | 410015 |
| 2 | Novartis Investigative Site | Guangzhou | Guangdong | China | 510060 |
| 3 | Novartis Investigative Site | Shantou | Guangdong | China | 515041 |
| 4 | Novartis Investigative Site | Harbin | Heilongjiang | China | 150001 |
| 5 | Novartis Investigative Site | Wuhan | Hubei | China | 430060 |
| 6 | Novartis Investigative Site | Wuhan | Hubei | China | 430070 |
| 7 | Novartis Investigative Site | Nanjing City | Jiangsu | China | 210000 |
| 8 | Novartis Investigative Site | Nantong | Jiangsu | China | 226000 |
| 9 | Novartis Investigative Site | Yixing | Jiangsu | China | 214299 |
| 10 | Novartis Investigative Site | Changchun City | Jilin | China | 130041 |
| 11 | Novartis Investigative Site | Shenyang City | Liaoning | China | 110000 |
| 12 | Novartis Investigative Site | Xian | Shaanxi | China | 710004 |
| 13 | Novartis Investigative Site | Jinan | Shandong | China | 250004 |
| 14 | Novartis Investigative Site | Tianjin | Tianjin | China | 300020 |
| 15 | Novartis Investigative Site | Tianjin | Tianjin | China | 300070 |
| 16 | Novartis Investigative Site | Hangzhou | Zhejiang | China | 310003 |
| 17 | Novartis Investigative Site | Hangzhou | Zhejiang | China | 310014 |
| 18 | Novartis Investigative Site | Beijing | China | 100034 | |
| 19 | Novartis Investigative Site | Beijing | China | 100044 | |
| 20 | Novartis Investigative Site | Beijing | China | 100050 | |
| 21 | Novartis Investigative Site | Beijing | China | 100191 | |
| 22 | Novartis Investigative Site | Beijing | China | 100730 | |
| 23 | Novartis Investigative Site | Chongqing | China | 400038 | |
| 24 | Novartis Investigative Site | Chongqing | China | 400042 | |
| 25 | Novartis Investigative Site | Nanjing | China | 210036 | |
| 26 | Novartis Investigative Site | Shanghai | China | 200031 | |
| 27 | Novartis Investigative Site | Shanghai | China | 200080 | |
| 28 | Novartis Investigative Site | Shanghai | China | 200092 | |
| 29 | Novartis Investigative Site | Shanghai | China |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRTH258A2307