End Stage Renal Disease Requiring Hemodialysis
Conditions
Keywords
End stage renal disease (ESRD), Hemodialysis (HD), Thrombotic Events
Brief summary
Patients whose kidneys are no longer able to work as they should and require treatment to filter wastes from the blood (hemodialysis) are at high risk for blood clots that form in blood vessels (thrombosis) blocking blood flow that causes heart attacks, strokes, and other life-threatening conditions. BAY2976217 is under clinical development for prevention of thrombosis. The goal of the study is to learn more about the safety of BAY2976217, how it is tolerated and the way the body absorbs, distributes and gets rid of the study dug given as multiple doses in participants with renal impairment who require hemodialysis.
Interventions
DRUGFesomersen sodium (BAY2976217)
Study intervention will be injected subcutaneously.
DRUGPlacebo
Matching placebo to BAY2976217 will be injected subcutaneously.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be at least 18 years of age at the time of signing the informed consent form (ICF) * Participants with ESRD on hemodialysis (HD) for ≥3 months at the time of signing of the ICF, receiving dialysis at least 9 hours a week and stable in the view of the investigator * Male or female (contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies) * Capable of giving signed ICF as described in the Protocol, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
Exclusion criteria
* Participants receiving antiplatelet therapy except daily acetylsalicylic acid (ASA) ≤ 150 mg/day * Participants receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure * Known inherited bleeding disorder e.g. von-Willebrand disease or Hemophilia A, B or C * Recent (\<6 months before screening) clinically significant bleeding, or at high risk of bleeding (in the judgement of the investigator) * Recent (\<3 months before screening) thromboembolic event, e.g. acute coronary syndrome, stroke, or Venous thromboembolism (except dialysis access thrombosis) * Recent (\<3 months before screening) major surgery or scheduled major surgery during participation in the study * Scheduled living donor renal transplant during study participation * Known Hepatitis B or C * Known HIV with recent documented detectable viral load (\<3 months before screening) * Persistent heart failure as classified by the New York Heart Association classification of 3 or higher * Life expectancy less than 6 months * Sustained uncontrolled hypertension (persistent measurements of diastolic blood pressure ≥ 100 mmHg, and/or systolic blood pressure ≥ 180 mmHg) * Hepatic disease associated with either: coagulopathy leading to a clinically relevant bleeding risk, or ALT \> 3x ULN, or total bilirubin \>2x ULN with direct bilirubin \> 20% of the total * Hb \< 9.0 g/dL at screening * Platelet count \< 120,000 mm\^3 at screening * Known hypersensitivity to the investigational drug or to inactive constituents of the study intervention * Active malignancy requiring treatment during study participation (except non-melanoma skin cancer, or cervical carcinoma in situ) * Participation in a study with an investigational medicinal product within 30 days or within 5 half-lives of the previous administered drug, whichever is longer, prior to the screening/observational period (Note: Participants from previous BAY2306001/ISIS 416858 and BAY2976217/ ION 957943 studies are eligible) * Any other conditions, which, in the opinion of the investigator or Sponsor would make the subject unsuitable for inclusion * Confirmed pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Up to 24 weeks | 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. |
| Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Up to 48 weeks | 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. |
| 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 | Up to 48 weeks | TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake. |
| 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 | Up to 48 weeks | 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. |
| Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period | Up to 24 weeks | 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. |
| Maximum Change in FXI Activity Levels During the Main Treatment Period | 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) | 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. |
| Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141) | 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. |
Countries
Belgium, Bulgaria, Canada, Czechia, Germany, Greece, Hungary, Japan, Latvia, Russia, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Recruitment details
Study was conducted at 69 study centers in 15 countries between 04-SEP-2020 (first participant first visit) and 12-MAY-2022 (last participant last visit).
Pre-assignment details
From 359 participants screened, 51 participants were screening failure and a total of 308 participants were randomized and 307 were treated either with fesomersen or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Fesomersen 40 mg Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide. | 77 |
| Fesomersen 80 mg Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide. | 79 |
| Fesomersen 120 mg Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide. | 76 |
| Placebo Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide. | 75 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Extension Treatment Period | Adverse Event | 0 | 1 | 0 | 1 |
| Extension Treatment Period | COVID-19 pandemic: Death | 0 | 0 | 0 | 1 |
| Extension Treatment Period | COVID-19 pandemic: withdrawal following protocol | 1 | 0 | 0 | 0 |
| Extension Treatment Period | Death | 0 | 0 | 1 | 2 |
| Extension Treatment Period | Other reason | 0 | 1 | 0 | 0 |
| Extension Treatment Period | Protocol-specified Withdrawal Criterion Met | 2 | 2 | 0 | 1 |
| Main Treatment Period | Adverse Event | 4 | 2 | 1 | 2 |
| Main Treatment Period | COVID-19 pandemic: Adverse event | 0 | 1 | 1 | 0 |
| Main Treatment Period | COVID-19 pandemic: Death | 0 | 1 | 0 | 2 |
| Main Treatment Period | COVID-19 pandemic: Participant decision | 0 | 1 | 0 | 0 |
| Main Treatment Period | COVID-19 pandemic: withdrawal following protocol | 1 | 3 | 3 | 1 |
| Main Treatment Period | Death | 1 | 0 | 0 | 1 |
| Main Treatment Period | Other reason | 1 | 1 | 0 | 0 |
| Main Treatment Period | Participant decision | 1 | 3 | 3 | 1 |
| Main Treatment Period | Physician Decision | 0 | 0 | 0 | 1 |
| Main Treatment Period | Protocol-specified withdrawal criterion met | 2 | 1 | 4 | 6 |
Baseline characteristics
| Characteristic | Fesomersen 40 mg | Fesomersen 80 mg | Fesomersen 120 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 13.2 | 58.0 Years STANDARD_DEVIATION 14.4 | 57.7 Years STANDARD_DEVIATION 13.3 | 58.6 Years STANDARD_DEVIATION 11.9 | 58.7 Years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 1 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 73 Participants | 75 Participants | 72 Participants | 294 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 8 Participants | 11 Participants | 13 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 62 Participants | 70 Participants | 61 Participants | 61 Participants | 254 Participants |
| Sex: Female, Male Female | 35 Participants | 20 Participants | 30 Participants | 22 Participants | 107 Participants |
| Sex: Female, Male Male | 42 Participants | 59 Participants | 46 Participants | 53 Participants | 200 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 77 | 1 / 79 | 2 / 76 | 7 / 75 |
| other Total, other adverse events | 31 / 77 | 27 / 79 | 30 / 76 | 21 / 75 |
| serious Total, serious adverse events | 19 / 77 | 18 / 79 | 17 / 76 | 20 / 75 |
Outcome results
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.
Time frame: Up to 24 weeks
Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fesomersen 40 mg | 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) | 9.0 n/100 person-years |
| Fesomersen 80 mg | 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) | 9.1 n/100 person-years |
| Fesomersen 120 mg | 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) | 6.1 n/100 person-years |
| Placebo | 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) | 9.7 n/100 person-years |
p-value: 0.94495% CI: [0.19, 4.68]Log Rank
p-value: 0.95395% CI: [0.19, 4.72]Log Rank
p-value: 0.60595% CI: [0.1, 3.75]Log Rank
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.
Time frame: Up to 48 weeks
Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fesomersen 40 mg | 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 | 10.7 n/100 person-years |
| Fesomersen 80 mg | 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 | 8.6 n/100 person-years |
| Fesomersen 120 mg | 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 | 6.4 n/100 person-years |
| Placebo | 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 | 7.0 n/100 person-years |
p-value: 0.61295% CI: [0.34, 6.08]Log Rank
p-value: 0.75795% CI: [0.28, 5.66]Log Rank
p-value: 0.90995% CI: [0.18, 4.52]Log Rank
Secondary
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.
Time frame: 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)
Population: Pharmacodynamic set (PDS) includes all participants with at least 1 PD sample in accordance with the PD sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PD data were included in the PD analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Baseline | 0.00 U/mL | Standard Deviation 0 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): Pre-dose | 0.06 U/mL | Standard Deviation 0.06 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 16 (Day 113): Pre-dose | 0.46 U/mL | Standard Deviation 0.26 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 14 (Day 85): Pre-dose | 0.46 U/mL | Standard Deviation 0.27 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 18 (Day 141): Pre-dose | 0.47 U/mL | Standard Deviation 0.27 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 20 (Day 155) | 0.52 U/mL | Standard Deviation 0.28 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 9 (Day 22) | 0.37 U/mL | Standard Deviation 0.26 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 12 (Day 57): Pre-dose | 0.42 U/mL | Standard Deviation 0.26 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 8 (Day 15) | 0.34 U/mL | Standard Deviation 0.23 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 6 (Day 2): 22 Hours | 0.13 U/mL | Standard Deviation 0.11 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): Pre-dose | 0.34 U/mL | Standard Deviation 0.26 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 13 (Day 71) | 0.52 U/mL | Standard Deviation 0.26 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): 5 Hours | 0.09 U/mL | Standard Deviation 0.09 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 19 (Day 148) | 0.52 U/mL | Standard Deviation 0.27 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): 5 Hours | 0.32 U/mL | Standard Deviation 0.25 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 21 (Day 162) | 0.50 U/mL | Standard Deviation 0.3 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 22 (Day 169): Pre-dose | 0.46 U/mL | Standard Deviation 0.29 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 7 (Day 8) | 0.21 U/mL | Standard Deviation 0.15 |
| Fesomersen 40 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 11 (Day 43) | 0.47 U/mL | Standard Deviation 0.29 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 7 (Day 8) | 0.32 U/mL | Standard Deviation 0.15 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 12 (Day 57): Pre-dose | 0.55 U/mL | Standard Deviation 0.24 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): 5 Hours | 0.11 U/mL | Standard Deviation 0.12 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 16 (Day 113): Pre-dose | 0.57 U/mL | Standard Deviation 0.28 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 13 (Day 71) | 0.66 U/mL | Standard Deviation 0.24 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 14 (Day 85): Pre-dose | 0.59 U/mL | Standard Deviation 0.26 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 21 (Day 162) | 0.64 U/mL | Standard Deviation 0.28 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 6 (Day 2): 22 Hours | 0.12 U/mL | Standard Deviation 0.12 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 22 (Day 169): Pre-dose | 0.59 U/mL | Standard Deviation 0.28 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 11 (Day 43) | 0.59 U/mL | Standard Deviation 0.25 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 20 (Day 155) | 0.65 U/mL | Standard Deviation 0.29 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 8 (Day 15) | 0.48 U/mL | Standard Deviation 0.21 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): Pre-dose | 0.05 U/mL | Standard Deviation 0.06 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 9 (Day 22) | 0.50 U/mL | Standard Deviation 0.23 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 19 (Day 148) | 0.63 U/mL | Standard Deviation 0.29 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): Pre-dose | 0.44 U/mL | Standard Deviation 0.21 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Baseline | 0.00 U/mL | Standard Deviation 0 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): 5 Hours | 0.43 U/mL | Standard Deviation 0.22 |
| Fesomersen 80 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 18 (Day 141): Pre-dose | 0.56 U/mL | Standard Deviation 0.28 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 20 (Day 155) | 0.77 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Baseline | 0.00 U/mL | Standard Deviation 0 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): Pre-dose | 0.05 U/mL | Standard Deviation 0.05 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): 5 Hours | 0.13 U/mL | Standard Deviation 0.13 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 6 (Day 2): 22 Hours | 0.15 U/mL | Standard Deviation 0.13 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 7 (Day 8) | 0.43 U/mL | Standard Deviation 0.18 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 8 (Day 15) | 0.61 U/mL | Standard Deviation 0.24 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 9 (Day 22) | 0.63 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): Pre-dose | 0.60 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): 5 Hours | 0.58 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 11 (Day 43) | 0.76 U/mL | Standard Deviation 0.27 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 12 (Day 57): Pre-dose | 0.69 U/mL | Standard Deviation 0.28 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 13 (Day 71) | 0.76 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 14 (Day 85): Pre-dose | 0.72 U/mL | Standard Deviation 0.24 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 16 (Day 113): Pre-dose | 0.75 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 18 (Day 141): Pre-dose | 0.72 U/mL | Standard Deviation 0.25 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 19 (Day 148) | 0.76 U/mL | Standard Deviation 0.26 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 21 (Day 162) | 0.75 U/mL | Standard Deviation 0.26 |
| Fesomersen 120 mg | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 22 (Day 169): Pre-dose | 0.73 U/mL | Standard Deviation 0.25 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 11 (Day 43) | 0.09 U/mL | Standard Deviation 0.08 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): 5 Hours | 0.12 U/mL | Standard Deviation 0.14 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): Pre-dose | 0.04 U/mL | Standard Deviation 0.05 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 18 (Day 141): Pre-dose | 0.12 U/mL | Standard Deviation 0.09 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 10 (Day 29): Pre-dose | 0.09 U/mL | Standard Deviation 0.07 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 9 (Day 22) | 0.11 U/mL | Standard Deviation 0.09 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Baseline | 0.00 U/mL | Standard Deviation 0 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 8 (Day 15) | 0.12 U/mL | Standard Deviation 0.09 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 7 (Day 8) | 0.08 U/mL | Standard Deviation 0.07 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 19 (Day 148) | 0.15 U/mL | Standard Deviation 0.16 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 20 (Day 155) | 0.15 U/mL | Standard Deviation 0.17 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 6 (Day 2): 22 Hours | 0.14 U/mL | Standard Deviation 0.13 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 5 (Day 1): 5 Hours | 0.10 U/mL | Standard Deviation 0.08 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 22 (Day 169): Pre-dose | 0.17 U/mL | Standard Deviation 0.21 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 14 (Day 85): Pre-dose | 0.14 U/mL | Standard Deviation 0.12 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 13 (Day 71) | 0.15 U/mL | Standard Deviation 0.13 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 12 (Day 57): Pre-dose | 0.11 U/mL | Standard Deviation 0.1 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 21 (Day 162) | 0.16 U/mL | Standard Deviation 0.2 |
| Placebo | Maximum Change in FXI Activity Levels During the Main Treatment Period | Visit 16 (Day 113): Pre-dose | 0.16 U/mL | Standard Deviation 0.16 |
Secondary
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.
Time frame: Up to 24 weeks
Population: Pharmacodynamic set (PDS) includes all participants with at least 1 PD sample in accordance with the PD sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PD data were included in the PD analysis. Data were not collected for this outcome measure.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period | Baseline | — |
| Unknown | Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period | Visit 5 (Day 1) | — |
Secondary
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.
Time frame: Up to 48 weeks
Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fesomersen 40 mg | 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 | Any TEAE | 64 Participants |
| Fesomersen 40 mg | 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 | Maximum intensity for any TEAE: Mild | 21 Participants |
| Fesomersen 40 mg | 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 | Maximum intensity for any TEAE: Moderate | 28 Participants |
| Fesomersen 40 mg | 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 | Maximum intensity for any TEAE: Severe | 15 Participants |
| Fesomersen 80 mg | 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 | Maximum intensity for any TEAE: Mild | 21 Participants |
| Fesomersen 80 mg | 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 | Maximum intensity for any TEAE: Moderate | 33 Participants |
| Fesomersen 80 mg | 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 | Maximum intensity for any TEAE: Severe | 9 Participants |
| Fesomersen 80 mg | 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 | Any TEAE | 63 Participants |
| Fesomersen 120 mg | 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 | Maximum intensity for any TEAE: Moderate | 33 Participants |
| Fesomersen 120 mg | 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 | Maximum intensity for any TEAE: Mild | 18 Participants |
| Fesomersen 120 mg | 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 | Maximum intensity for any TEAE: Severe | 11 Participants |
| Fesomersen 120 mg | 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 | Any TEAE | 62 Participants |
| Placebo | 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 | Maximum intensity for any TEAE: Severe | 16 Participants |
| Placebo | 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 | Maximum intensity for any TEAE: Mild | 21 Participants |
| Placebo | 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 | Any TEAE | 59 Participants |
| Placebo | 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 | Maximum intensity for any TEAE: Moderate | 22 Participants |
Secondary
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.
Time frame: Up to 48 weeks
Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fesomersen 40 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 26 Participants |
| Fesomersen 40 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 11 Participants |
| Fesomersen 40 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Any TEAE | 61 Participants |
| Fesomersen 40 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 24 Participants |
| Fesomersen 80 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Any TEAE | 62 Participants |
| Fesomersen 80 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 6 Participants |
| Fesomersen 80 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 25 Participants |
| Fesomersen 80 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 31 Participants |
| Fesomersen 120 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Any TEAE | 58 Participants |
| Fesomersen 120 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 8 Participants |
| Fesomersen 120 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 30 Participants |
| Fesomersen 120 mg | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 20 Participants |
| Placebo | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 12 Participants |
| Placebo | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 26 Participants |
| Placebo | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 18 Participants |
| Placebo | Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity | Any TEAE | 56 Participants |
Secondary
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.
Time frame: Up to 24 weeks
Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fesomersen 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Any TEAE | 54 Participants |
| Fesomersen 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 28 Participants |
| Fesomersen 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 17 Participants |
| Fesomersen 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 9 Participants |
| Fesomersen 80 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 28 Participants |
| Fesomersen 80 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 24 Participants |
| Fesomersen 80 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 4 Participants |
| Fesomersen 80 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Any TEAE | 56 Participants |
| Fesomersen 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 28 Participants |
| Fesomersen 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 22 Participants |
| Fesomersen 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 5 Participants |
| Fesomersen 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Any TEAE | 55 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Severe | 9 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Mild | 27 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Any TEAE | 55 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity | Maximum intensity for any TEAE: Moderate | 19 Participants |
Secondary
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.
Time frame: At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)
Population: Pharmacokinetic analysis set (PKS) includes all fesomersen-treated participants with at least 1 PK sample in accordance with the PK sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PK data were included in the PK analysis. Only those participants who have sample collection with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Fesomersen 40 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 12 | 0.000454 μg/mL | Geometric Coefficient of Variation 118.753791 |
| Fesomersen 40 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 14 | 0.000490 μg/mL | Geometric Coefficient of Variation 92.511801 |
| Fesomersen 40 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 16 | 0.000572 μg/mL | Geometric Coefficient of Variation 85.974878 |
| Fesomersen 40 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 18 | 0.000521 μg/mL | Geometric Coefficient of Variation 106.848825 |
| Fesomersen 80 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 18 | 0.000828 μg/mL | Geometric Coefficient of Variation 91.024162 |
| Fesomersen 80 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 12 | 0.000704 μg/mL | Geometric Coefficient of Variation 80.938271 |
| Fesomersen 80 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 16 | 0.000789 μg/mL | Geometric Coefficient of Variation 68.188121 |
| Fesomersen 80 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 14 | 0.000792 μg/mL | Geometric Coefficient of Variation 82.170296 |
| Fesomersen 120 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 18 | 0.001424 μg/mL | Geometric Coefficient of Variation 92.709743 |
| Fesomersen 120 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 14 | 0.001246 μg/mL | Geometric Coefficient of Variation 97.53082 |
| Fesomersen 120 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 16 | 0.001346 μg/mL | Geometric Coefficient of Variation 81.80568 |
| Fesomersen 120 mg | Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen | Visit 12 | 0.001186 μg/mL | Geometric Coefficient of Variation 76.691406 |