E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
End Stage Renal Disease requiring hemodialysis |
|
E.1.1.1 | Medical condition in easily understood language |
Kidneys are no longer able to work as they should and require treatment to filter wastes and water from the blood |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10077512 |
E.1.2 | Term | End stage renal disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019480 |
E.1.2 | Term | Hemodialysis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066639 |
E.1.2 | Term | Myocardial infarct prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049165 |
E.1.2 | Term | Cerebrovascular accident prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of BAY2976217 compared to placebo |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the PK and PD of BAY2976217 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Two types of PK/PD sampling will be performed: regular PK/PD sampling in the majority of the participants, and alternative PK/PD sampling in a subset of approximately 24-40 participants. |
|
E.3 | Principal inclusion criteria |
- Participant must be at least 18 years of age at the time of signing the ICF.
- Participants with ESRD on 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 |
|
E.4 | Principal exclusion criteria |
- Participants receiving antiplatelet therapy except daily 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 VTE (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 mm3 at screening
- Known hypersensitivity to the investigational drug or to inactive constituents of the study intervention
- Active malignancy requiring treatment during study participation (except nonmelanoma 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 BAY 2306001/ISIS 416858 and BAY 2976217 / 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of major bleeding and clinically-relevant non-major bleeding during the main treatment period and within the on-treatment time window, as assessed by blinded Central Independent Adjudication Committee (CIAC) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1- Incidence of composite of major bleeding and clinically-relevant non major bleeding during the main and extended treatment periods and within the on-treatment time window, as assessed by blinded CIAC
2- Number of participants with treatment-emergent adverse events (TEAEs) during the main treatment period and within the on-treatment time window
3- Number of participants with TEAEs during the main and extended treatment periods and within the on-treatment time window
4- Number of participants with TEAEs during the main and extended treatment periods and until 20 weeks after the last study intervention dose
5- Number of participants with TEAEs categorized by severity during the main treatment period and within the on-treatment time window
6- Number of participants with TEAEs categorized by severity during the main and extended treatment periods and within the on-treatment time window
7- Number of participants with TEAEs categorized by severity during the main and extended treatment periods and until 20 weeks after the last study intervention dose
8- Trough concentrations for 3 dose levels of BAY 2976217
9- Maximum change in FXI antigen levels during the main treatment period
10- Maximum change in FXI activity levels during the main treatment period |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Up to 48 weeks
2- Up to 24 weeks
3- Up to 48 weeks
4- Up to 64 weeks
5- Up to 24 weeks
6- Up to 48 weeks
7- Up to 64 weeks
8- At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)
9- Up to 24 weeks
10- Up to 24 weeks |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Japan |
Korea, Republic of |
Russian Federation |
Taiwan |
Ukraine |
United States |
Belgium |
Bulgaria |
Germany |
Hungary |
Latvia |
Spain |
Czechia |
Greece |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |