| Outcome Measures: |
Primary: Incidence of Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) During the Main Treatment Period and Within the On-treatment Time Window, as Assessed by Blinded Central Independent Adjudication Committee (CIAC), MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred., Up to 24 weeks | Secondary: Incidence of Composite of MB and CRNMB During the Main and Extended Treatment Periods and Within the On-treatment Time Window, as Assessed by Blinded CIAC, MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred., Up to 48 weeks|Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity, TEAEs were analyzed during the on-treatment time window within the main treatment period in the safety analysis set (SAF). Data observed from the randomization date until the end of the main treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration., Up to 24 weeks|Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity, TEAEs were analyzed during during main and extended treatment periods in the safety analysis set (SAF). Data observed from the randomization date until the end of the extension treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration., Up to 48 weeks|Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity, TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake., Up to 48 weeks|Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen, Trough (pre-dose) fesomersen-equivalent plasma concentrations (Ctrough) for 3 dose levels of fesomersen were summarized descriptively by dose level and visit: Visit 12, Visit 14, Visit 16, Visit 18 (main treatment period). Ctrough was not measured for the placebo group., At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)|Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period, The secondary endpoint of change in FXI antigen levels during the main treatment period was an optional secondary endpoint only as mentioned in the integrated clinical protocol amendment version 3.0 and was not analyzed in this study as the FXI activity assay is sufficient to describe the effect on FXI level in plasma., Up to 24 weeks|Maximum Change in FXI Activity Levels During the Main Treatment Period, The FXIa activity was measured by a fluorogenic activated FXIa activity (AXIA) assay. Absolute change from baseline at each visit until Visit 22 (Day 169) are reported., Baseline, Days 1 (Pre-Dose and 5 hours post-dose), 2, 8, 15, 22, 29 (Pre-dose and 5 hours post-dose), 43, 57 (Pre-dose), 71, 85 (Pre-dose), 113 (Pre-dose), 141 (Pre-dose),148, 155, 162, and 169 (Pre-dose)
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| Locations: |
Fresenius Kidney Care Clovis, Clovis, California, 93611, United States|Desert Cities Dialysis-Amethyst & Desert Cities Dialysis, Victorville, California, 92392, United States|Davita East Ft. Lauderdale Dialysis Center, Fort Lauderdale, Florida, 33316, United States|Fresenius Kidney Care St. Louis Regional Dialysis, Saint Ann, Missouri, 63074, United States|Chromalloy Dialysis Center, Saint Louis, Missouri, 63110, United States|Fresenius Medical Care - Fire Mesa Dialysis Unit, Las Vegas, Nevada, 89128, United States|DaVita Northwest Medical Center Dialysis, San Antonio, Texas, 78229, United States|San Antonio Kidney Disease Center Physicians Group, PLLC, San Antonio, Texas, 78258, United States|Salem VA Medical Center, Salem, Virginia, 24153, United States|OL Vrouwziekenhuis - Campus Aalst, Aalst, 9300, Belgium|UZ Brussel, Bruxelles - Brussel, 1090, Belgium|UZ Antwerpen, Edegem, 2650, Belgium|Regionaal ZH Jan Yperman Campus Mariaziekenhuis, Ieper, 8900, Belgium|First Dialysis Services Bulgaria Ead, Montana, 3400, Bulgaria|MHAT Samokov, Samokov, 2000, Bulgaria|MHAT "Knyaginya Klementina - Sofia"EAD, Sofia, 1233, Bulgaria|MHAT National Cardiology Hospital EAD, Sofia, 1309, Bulgaria|Etobicoke General Hospital, Etobicoke, Ontario, M9V 1R8, Canada|St. Joseph's Healthcare - Hamilton, Hamilton, Ontario, L8N 4A6, Canada|Lakeridge Health-Oshawa, Oshawa, Ontario, L1G 2B9, Canada|Unity Health Toronto: St. Michael's Hospital, Toronto, Ontario, M5B 1W8, Canada|Centre de services ambulatoires de dialyse de Gaspé, Montreal, Quebec, H2T 3B3, Canada|CHU de Québec-Université Laval, Quebec, G1J 1Z4, Canada|Nemocnice Frydek-Mistek, Frydek-Mistek, 738 01, Czechia|Klatovska nemocnice, Klatovy, 339 01, Czechia|Fresenius Medical Care - DS, s.r.o., Melnik, 276 01, Czechia|Oblastni nemocnice Mlada Boleslav, Mlada Boleslav, 293 50, Czechia|DaVita Clinical Research Deutschland GmbH, Duesseldorf, Nordrhein-Westfalen, 40210, Germany|DaVita Clinical Resarch Germany GmbH, Geilenkirchen, Nordrhein-Westfalen, 52511, Germany|Universitätsklinikum Schleswig-Holstein (UKSH), Kiel, Schleswig-Holstein, 24105, Germany|University General Hospital of Heraklion, Heraklion, 711 10, Greece|University General Hospital of Patra, Patra, 26504, Greece|PAPANIKOLAOU General Hospital Thessaloniki, Pilea Chortiatis, 57010, Greece|Bacs-Kiskun Megyei Korhaz, Kalocsa, 6300, Hungary|SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont, Szeged, 6720, Hungary|Matsunami General Hospital, Hashima-gun, Gifu, 501-6062, Japan|Sapporo Tokushukai Hospital, Sapporo, Hokkaido, 004-0041, Japan|Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, 309-1793, Japan|Public Central Hospital of Matto Ishikawa, Hakusan, Ishikawa, 924-8588, Japan|Shonan Fujisawa Tokushukai Hospital, Fujisawa, Kanagawa, 251-0041, Japan|Hanyu General Hospital, Hanyu, Saitama, 348-0045, Japan|Medical corporation association Shunshin-kai Inage hospital, Chiba, 263-0043, Japan|The Catholic University of Korea, Incheon St.Mary's Hospital, Incheon, Incheon Gwang''yeogsi, 21431, Korea, Republic of|Yeouido St. Mary's Hospital, Seoul, Seoul Teugbyeolsi, 150-713, Korea, Republic of|Daugavpils Regional Hospital, Daugavpils, LV-5417, Latvia|Liepaja Regional Hospital, Liepaja, LV-3414, Latvia|P. Stradins Clinical University Hospital, Riga, LV-1002, Latvia|Vidzemes Hospital, Valmiera, LV-4201, Latvia|High Technology Center Clinic 1, Moscow, 125466, Russian Federation|Limited Liability Company "Nefroline-Novosibirsk", Novosibirsk, 630064, Russian Federation|LLC Frezenius Nefrocare, Penza, 440034, Russian Federation|LLC Dialysis center, Podolsk, 142110, Russian Federation|Nikiforov All-Russian Center of Emergency and Radiation Med, Saint-Petersburg, 197374, Russian Federation|Botkin clinical infectious diseases hospital, St. Petersburg, 195067, Russian Federation|LLC B. Brown Avitum Russland Clinics, St. Petersburg, 196247, Russian Federation|State Budgetary Healthcare Institution City Hospital #26, St. Petersburg, 196247, Russian Federation|Hospital Principe de Asturias, Alcalá de Henares, Madrid, 28805, Spain|Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention, Barcelona, 08907, Spain|Hospital Clínic i Provincial de Barcelona, Barcelona, 8036, Spain|Hospital Universitario Virgen de las Nieves|Nefrologia, Granada, 18014, Spain|Hospital Universitari i Politècnic La Fe | Nefrología, Valencia, 46026, Spain|Chi Mei Medical Center, Tainan, 710, Taiwan|Taipei Medical University Hospital, Taipei, 110, Taiwan|Medical Center Fresenius Medical Care Ukraine, LLC, Chernigiv, 14034, Ukraine|Kyiv City Center of Nephrology and Dialysis, Kyiv, 01023, Ukraine|Kyiv Regional Clinical Hospital, Kyiv, 04107, Ukraine|Regional Clinical Hospital - Odessa, Odesa, 65025, Ukraine|Ternopil Regional Clinical Hospital, Ternopil, 46002, Ukraine|Zaporizhia Municipal Clinical Hospital No.10, Zaporizhzhya, 69001, Ukraine
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