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NCT04534114: RE-THINc ESRD

Factor XI LICA to Reduce Events Such as Heart Attack and Stroke in Patients Whose Kidneys Are no Longer Able to Work as They Should and Require Treatment to Filter Wastes From the Blood: Focus is on the Safety of BAY2976217 and the Way the Body Absorbs, Distributes and Removes the Study Drug

Completed Phase 2 Results posted Last updated 3 July 2023
What this trial tests

Phase 2 trial testing Fesomersen sodium (BAY2976217) in End Stage Renal Disease Requiring Hemodialysis in 307 participants. Completed in 12 May 2022.

Timeline
4 September 2020
Primary endpoint
24 January 2022
12 May 2022

Quick facts

Lead sponsorBayer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment307
Start date4 September 2020
Primary completion24 January 2022
Estimated completion12 May 2022
Sites69 locations across Japan, Russia, Greece, Ukraine, Belgium, Taiwan, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with End Stage Renal Disease Requiring Hemodialysis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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 cri

GroupValue95% CI
Fesomersen 40 mg9.02.5 – 18.9
Fesomersen 80 mg9.12.5 – 19.1
Fesomersen 120 mg6.11.1 – 14.5
Placebo9.72.7 – 20.4
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 Secondary · 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 cri

GroupValue95% CI
Fesomersen 40 mg10.74.2 – 19.7
Fesomersen 80 mg8.62.9 – 16.7
Fesomersen 120 mg6.41.7 – 13.3
Placebo7.01.9 – 14.8
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity Secondary · 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.

Any TEAE
GroupValue95% CI
Fesomersen 40 mg54
Fesomersen 80 mg56
Fesomersen 120 mg55
Placebo55
Maximum intensity for any TEAE: Mild
GroupValue95% CI
Fesomersen 40 mg28
Fesomersen 80 mg28
Fesomersen 120 mg22
Placebo27
Maximum intensity for any TEAE: Moderate
GroupValue95% CI
Fesomersen 40 mg17
Fesomersen 80 mg24
Fesomersen 120 mg28
Placebo19
Maximum intensity for any TEAE: Severe
GroupValue95% CI
Fesomersen 40 mg9
Fesomersen 80 mg4
Fesomersen 120 mg5
Placebo9
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity Secondary · 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.

Any TEAE
GroupValue95% CI
Fesomersen 40 mg61
Fesomersen 80 mg62
Fesomersen 120 mg58
Placebo56
Maximum intensity for any TEAE: Mild
GroupValue95% CI
Fesomersen 40 mg26
Fesomersen 80 mg25
Fesomersen 120 mg20
Placebo26
Maximum intensity for any TEAE: Moderate
GroupValue95% CI
Fesomersen 40 mg24
Fesomersen 80 mg31
Fesomersen 120 mg30
Placebo18
Maximum intensity for any TEAE: Severe
GroupValue95% CI
Fesomersen 40 mg11
Fesomersen 80 mg6
Fesomersen 120 mg8
Placebo12
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 Secondary · Up to 48 weeks

TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake.

Any TEAE
GroupValue95% CI
Fesomersen 40 mg64
Fesomersen 80 mg63
Fesomersen 120 mg62
Placebo59
Maximum intensity for any TEAE: Mild
GroupValue95% CI
Fesomersen 40 mg21
Fesomersen 80 mg21
Fesomersen 120 mg18
Placebo21
Maximum intensity for any TEAE: Moderate
GroupValue95% CI
Fesomersen 40 mg28
Fesomersen 80 mg33
Fesomersen 120 mg33
Placebo22
Maximum intensity for any TEAE: Severe
GroupValue95% CI
Fesomersen 40 mg15
Fesomersen 80 mg9
Fesomersen 120 mg11
Placebo16
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen Secondary · 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.

Visit 12
GroupValue95% CI
Fesomersen 40 mg0.000454± 118.753791
Fesomersen 80 mg0.000704± 80.938271
Fesomersen 120 mg0.001186± 76.691406
Visit 14
GroupValue95% CI
Fesomersen 40 mg0.000490± 92.511801
Fesomersen 80 mg0.000792± 82.170296
Fesomersen 120 mg0.001246± 97.530820
Visit 16
GroupValue95% CI
Fesomersen 40 mg0.000572± 85.974878
Fesomersen 80 mg0.000789± 68.188121
Fesomersen 120 mg0.001346± 81.805680
Visit 18
GroupValue95% CI
Fesomersen 40 mg0.000521± 106.848825
Fesomersen 80 mg0.000828± 91.024162
Fesomersen 120 mg0.001424± 92.709743
Maximum Change in FXI Activity Levels During the Main Treatment Period Secondary · 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.

Baseline
GroupValue95% CI
Fesomersen 40 mg0.00± 0.00
Fesomersen 80 mg0.00± 0.00
Fesomersen 120 mg0.00± 0.00
Placebo0.00± 0.00
Visit 5 (Day 1): Pre-dose
GroupValue95% CI
Fesomersen 40 mg0.06± 0.06
Fesomersen 80 mg0.05± 0.06
Fesomersen 120 mg0.05± 0.05
Placebo0.04± 0.05
Visit 5 (Day 1): 5 Hours
GroupValue95% CI
Fesomersen 40 mg0.09± 0.09
Fesomersen 80 mg0.11± 0.12
Fesomersen 120 mg0.13± 0.13
Placebo0.10± 0.08
Visit 6 (Day 2): 22 Hours
GroupValue95% CI
Fesomersen 40 mg0.13± 0.11
Fesomersen 80 mg0.12± 0.12
Fesomersen 120 mg0.15± 0.13
Placebo0.14± 0.13
Visit 7 (Day 8)
GroupValue95% CI
Fesomersen 40 mg0.21± 0.15
Fesomersen 80 mg0.32± 0.15
Fesomersen 120 mg0.43± 0.18
Placebo0.08± 0.07
Visit 8 (Day 15)
GroupValue95% CI
Fesomersen 40 mg0.34± 0.23
Fesomersen 80 mg0.48± 0.21
Fesomersen 120 mg0.61± 0.24
Placebo0.12± 0.09
Visit 9 (Day 22)
GroupValue95% CI
Fesomersen 40 mg0.37± 0.26
Fesomersen 80 mg0.50± 0.23
Fesomersen 120 mg0.63± 0.25
Placebo0.11± 0.09
Visit 10 (Day 29): Pre-dose
GroupValue95% CI
Fesomersen 40 mg0.34± 0.26
Fesomersen 80 mg0.44± 0.21
Fesomersen 120 mg0.60± 0.25
Placebo0.09± 0.07

Adverse events — posted to ClinicalTrials.gov

Time frame: From first study intervention up to 64 Weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fesomersen 40 mg
Serious: 19/77 (25%)
Deaths: 2/77
Fesomersen 80 mg
Serious: 18/79 (23%)
Deaths: 1/79
Fesomersen 120 mg
Serious: 17/76 (22%)
Deaths: 2/76
Placebo
Serious: 20/75 (27%)
Deaths: 7/75

Serious adverse events (79 terms)

ReactionSystemFesomersen 40 mgFesomersen 80 mgFesomersen 120 mgPlacebo
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Renal transplantSurgical and medical procedures
Arteriovenous fistula thrombosisInjury, poisoning and procedural complications
CellulitisInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
Spleen ischaemiaBlood and lymphatic system disorders
ArrhythmiaCardiac disorders
Atrial fibrillationCardiac disorders
Atrial flutterCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failure congestiveCardiac disorders
Coronary artery diseaseCardiac disorders
Supraventricular tachycardiaCardiac disorders
Ventricular fibrillationCardiac disorders
BradyarrhythmiaCardiac disorders
Acute coronary syndromeCardiac disorders
Abdominal adhesionsGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Duodenal ulcer haemorrhageGastrointestinal disorders
GastritisGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal ischaemiaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Large intestine perforationGastrointestinal disorders
Other adverse events (12 terms — click to expand)

ReactionSystemFesomersen 40 mgFesomersen 80 mgFesomersen 120 mgPlacebo
HypotensionVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
N-terminal prohormone brain natriuretic peptide increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: COVID-19, COVID-19 pneumonia, Renal transplant, Arteriovenous fistula thrombosis, Cellulitis, Thrombocytopenia, Spleen ischaemia, Arrhythmia.

Data from ClinicalTrials.gov NCT04534114 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence.
    Nopp S, Kraemmer D, Ay C. · · 2022 · cited 61× · PMID 35647061 · DOI 10.3389/fcvm.2022.903029
  2. RNA Therapeutics: the Next Generation of Drugs for Cardiovascular Diseases.
    Bejar N, Tat TT, Kiss DL. · · 2022 · cited 32× · PMID 35364795 · DOI 10.1007/s11883-022-01007-9
  3. PK/PD modeling of FXI antisense oligonucleotides to bridge the dose-FXI activity relation from healthy volunteers to end-stage renal disease patients.
    Willmann S, Marostica E, Snelder N, Solms A, et al · · 2021 · cited 32× · PMID 34085768 · DOI 10.1002/psp4.12663
  4. Factor XI Inhibition for the Prevention of Venous Thromboembolism: An Update on Current Evidence and Future perspectives.
    Poenou G, Dumitru Dumitru T, Lafaie L, Mismetti V, et al · · 2022 · cited 26× · PMID 35707632 · DOI 10.2147/vhrm.s331614
  5. New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.
    Tamargo J, Agewall S, Borghi C, Ceconi C, et al · · 2023 · cited 25× · PMID 37169875 · DOI 10.1093/ehjcvp/pvad034
  6. Treatment of Cancer-Associated Thrombosis: Recent Advances, Unmet Needs, and Future Direction.
    Wang TF, Khorana AA, Agnelli G, Bloomfield D, et al · · 2023 · cited 23× · PMID 37171998 · DOI 10.1093/oncolo/oyad116
  7. Hepatocyte targeting <i>via</i> the asialoglycoprotein receptor.
    Ramírez-Cortés F, Ménová P. · · 2025 · cited 22× · PMID 39628900 · DOI 10.1039/d4md00652f
  8. A Phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis.
    Winkelmayer WC, Lensing AWA, Thadhani RI, Mahaffey KW, et al · · 2024 · cited 21× · PMID 38537676 · DOI 10.1016/j.kint.2024.02.024

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