Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration : The Phase 2 CANDELA Randomized Clinical Trial
Importance: Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden.
Objective: To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD.
Design, Setting, and Participants: The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021.
Interventions: Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32.
Main Outcomes and Measures: Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety.
Results: All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed.
Conclusions and Relevance: Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema.
Trial Registration: ClinicalTrials.gov Identifier: NCT04126317.
| Errataetall: |
CommentIn: JAMA Ophthalmol. 2023 Sep 1;141(9):843. - PMID 37535346 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:141 |
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| Enthalten in: |
JAMA ophthalmology - 141(2023), 9 vom: 01. Sept., Seite 834-842 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wykoff, Charles C [VerfasserIn] |
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| Links: |
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| Themen: |
15C2VL427D |
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| Anmerkungen: |
Date Completed 22.09.2023 Date Revised 06.03.2024 published: Print ClinicalTrials.gov: NCT04126317 CommentIn: JAMA Ophthalmol. 2023 Sep 1;141(9):843. - PMID 37535346 Citation Status MEDLINE |
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| doi: |
10.1001/jamaophthalmol.2023.2421 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration |b The Phase 2 CANDELA Randomized Clinical Trial |
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| 500 | |a ClinicalTrials.gov: NCT04126317 | ||
| 500 | |a CommentIn: JAMA Ophthalmol. 2023 Sep 1;141(9):843. - PMID 37535346 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden | ||
| 520 | |a Objective: To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD | ||
| 520 | |a Design, Setting, and Participants: The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021 | ||
| 520 | |a Interventions: Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32 | ||
| 520 | |a Main Outcomes and Measures: Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety | ||
| 520 | |a Results: All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed | ||
| 520 | |a Conclusions and Relevance: Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema | ||
| 520 | |a Trial Registration: ClinicalTrials.gov Identifier: NCT04126317 | ||
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| 700 | 1 | |a Berliner, Alyson J |e verfasserin |4 aut | |
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| 700 | 1 | |a Gonzalez Ramos, Astrid |e investigator |4 oth | |
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| 700 | 1 | |a Adrean, Sean |e investigator |4 oth | |
| 700 | 1 | |a Payne, John |e investigator |4 oth | |
| 700 | 1 | |a Brooks, Harold |e investigator |4 oth | |
| 700 | 1 | |a Chittum, Mark |e investigator |4 oth | |
| 700 | 1 | |a Callanan, David |e investigator |4 oth | |
| 700 | 1 | |a Paylor, Ralph |e investigator |4 oth | |
| 700 | 1 | |a Chan, Clement |e investigator |4 oth | |
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| 700 | 1 | |a Chaudhry, Nauman |e investigator |4 oth | |
| 700 | 1 | |a Chang, Margaret |e investigator |4 oth | |
| 700 | 1 | |a Chen, Sanford |e investigator |4 oth | |
| 700 | 1 | |a Bridges, William |e investigator |4 oth | |
| 700 | 1 | |a Dooner, James |e investigator |4 oth | |
| 700 | 1 | |a Solley, Wayne |e investigator |4 oth | |
| 700 | 1 | |a Emanuelli, Andres |e investigator |4 oth | |
| 700 | 1 | |a Teed, Ronald |e investigator |4 oth | |
| 700 | 1 | |a Friedman, Scott |e investigator |4 oth | |
| 700 | 1 | |a Moinfar, Nader |e investigator |4 oth | |
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