Francesca Castagnoli, Justin Mencel, Derfel Ap Dafydd, Jessica Gough, Brent Drake, Naami Charlotte Mcaddy, Samuel Joseph Withey, Angela Mary Riddell, Dow-Mu Koh, Joshua David Shur
Response Evaluation Criteria in Gastrointestinal and Abdominal Cancers: Which to Use and How to Measure
Radiographics : a review publication of the Radiological Society of North America, Inc
garadacimab fully human immunoglobulin g4 monoclonal antibody targeting activated factor xii study evaluated longterm efficacy healthrelated quality life hrqol safety data garadacimab adults hereditary angioedema global phase 2 study comprised treatment period 1 tp1 12 weeks doubleblind placebocontrolled treatment period 2 tp2 44week openlabel extension patients aged 1865 years clinically confirmed hereditary angioedema eligible tp1 32 patients randomly assigned 1111 receive subcutaneous garadacimab 75 mg 200 mg 600 mg placebo every 4 weeks monthly randomisation done using interactive response technology via block randomisation block sizes 14 subsequently six additional patients tp1 assigned openlabel garadacimab 400 mg every 2 weeks start tp2 patients rerandomised receiving placebo garadacimab 75 mg garadacimab 400 mg continued receive garadacimab 200 mg garadacimab 600 mg monthly protocol amendment march 20 2020 patients originally assigned 600 mg dose downtitrated 200 mg next visit primary endpoint published previously monthly attack rate patients receiving 200 mg 600 mg garadacimab tp1 intentiontotreat population assessed impact garadacimab patientreported investigatorreported outcomes hrqol well longterm efficacy safety trial registered clinicaltrialsgov nct03712228 completed 54 patients screened oct 29 2018 aug 28 2019 32 randomised six openlabel patients completed tp1 entered tp2 20 garadacimab 200 mg group 18 garadacimab 600 mg group total 38 patients median age 390 years iqr 270530 21 patients 55 female 17 45 male tp2 median garadacimab exposure 879 weeks iqr 5001066 garadacimab 200 mg group 441 weeks 241561 garadacimab 600 mg group median monthly attack rates 00 iqr 0001 garadacimab 200 mg group 01 0004 garadacimb 600 mg group median reduction monthly attack rate versus runin 100 iqr 98100 garadacimab 200 mg hrqol improvements observed tp1 garadacimab sustained throughout tp2 tp2 safety signals consistent tp1 two patients experienced serious adverse events diverticular perforation asthma garadacimabrelated treatmentemergent adverse events mostly mild moderate severity common adverse events headache nine 38 24 abdominal pain seven 38 18 treatmentrelated deaths oncemonthly garadacimab 2 years patients hereditary angioedema well tolerated efficacious reducing monthly attack rate improving hrqol results reveal potential longterm prophylactic treatment 200 mg oncemonthly garadacimab towards complete disease control patients hereditary angioedema csl behring