TY - JOUR
T1 - Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration
T2 - Chroma and spectri phase 3 randomized clinical trials
AU - the Chroma and Spectri Study Investigators
AU - Holz, Frank G.
AU - Sadda, Srinivas R.
AU - Busbee, Brandon
AU - Chew, Emily Y.
AU - Mitchell, Paul
AU - Tufail, Adnan
AU - Brittain, Christopher
AU - Ferrara, Daniela
AU - Gray, Sarah
AU - Honigberg, Lee
AU - Martin, Jillian
AU - Tong, Barbara
AU - Ehrlich, Jason S.
AU - Bressler, Neil M.
AU - Sola, Federico Furno
AU - Schlottmann, Patricio
AU - Zambrano, Alberto
AU - Zeolite, Carlos
AU - Arnold, Jennifer
AU - Gillies, Mark
AU - Luckie, Alan
AU - Mitchell, Paul
AU - Schneltzer, Nicole
AU - de Zaeytijd, Julie
AU - Boyd, Shelley
AU - Cruess, Alan
AU - Kertes, Peter
AU - Lalonde, Laurent
AU - Maberley, David
AU - Laugesen, Caroline
AU - Bodaghi, Bahram
AU - Cohen, Salomon Yves
AU - Francais, Catherine
AU - Souied, Eric
AU - Tadayoni, Ramin
AU - Altay, Lebriz
AU - Eter, Nicole
AU - Feltgen, Nicolas
AU - Framme, Carsten
AU - Grisanti, Salvatore
AU - Pauleikhoff, Daniel
AU - Seres, András
AU - Vajas, Attila
AU - Varsanyi, Balazs
AU - Boscia, Francesco
AU - Parravano, Maria Cristina
AU - Ricci, Federico
AU - Viola, Francesco
AU - Rechy, David Lozano
AU - Ufret-Vincenty, Rafael
N1 - Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/6
Y1 - 2018/6
N2 - IMPORTANCE Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials. OBJECTIVE To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA. DESIGN, SETTING, AND PARTICIPANTS Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm2 with diffuse or banded fundus autofluorescence patterns. INTERVENTIONS Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks. MAIN OUTCOMES AND MEASURES Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I-profile genetic biomarker. RESULTS A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm2 across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were -0.02 mm2 (95% CI, -0.21 to 0.16 mm2; P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm2 (95% CI, 0.00-0.31 mm2; P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm2 (95% CI, -0.13 to 0.24 mm2; P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm2 (95% CI, -0.07 to 0.24 mm2; P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I-profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48. CONCLUSIONS AND RELEVANCE In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm2 per year.
AB - IMPORTANCE Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials. OBJECTIVE To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA. DESIGN, SETTING, AND PARTICIPANTS Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm2 with diffuse or banded fundus autofluorescence patterns. INTERVENTIONS Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks. MAIN OUTCOMES AND MEASURES Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I-profile genetic biomarker. RESULTS A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm2 across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were -0.02 mm2 (95% CI, -0.21 to 0.16 mm2; P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm2 (95% CI, 0.00-0.31 mm2; P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm2 (95% CI, -0.13 to 0.24 mm2; P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm2 (95% CI, -0.07 to 0.24 mm2; P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I-profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48. CONCLUSIONS AND RELEVANCE In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm2 per year.
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U2 - 10.1001/jamaophthalmol.2018.1544
DO - 10.1001/jamaophthalmol.2018.1544
M3 - Article
C2 - 29801123
AN - SCOPUS:85048747589
SN - 2168-6165
VL - 136
SP - 666
EP - 677
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
IS - 6
ER -