E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Venous Thromboembolic Event |
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E.1.1.1 | Medical condition in easily understood language |
prevention (prophylaxis) of blood clots, called venous thromboembolic events (deep vein thrombosis and/or pulmonary embolism) which may occur as a result of total hip replacement surgery |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
The primary objective is to evaluate the safety and efficacy of two doses of TB-402 administered as a single intravenous infusion for the prevention of VTE in subjects undergoing total hip replacement surgery. |
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E.2.2 | Secondary objectives of the trial |
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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 |
A PK/PD sub study will be performed at selected sites, to develop a more detailed understanding of the pharmacokinetics (TB-402 levels) and pharmacodynamics (FVIII:c, FVIII:Ag, thrombin generation) of TB-402. The substudy will be done in up to 300 subjects (up to 100 per treatment arm). |
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E.3 | Principal inclusion criteria |
1. Male or female subjects aged ≥ 18 years old scheduled for elective total hip replacement surgery.
2. Written informed consent.
3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
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E.4 | Principal exclusion criteria |
1. Pregnancy at the time of screening based on a urine or blood pregnancy test or not using a reliable method of birth control.
2. Indication for anticoagulation other than post-operative thromboprophylaxis.
3. Active bleeding or high risk of bleeding contraindicating anticoagulant treatment according to the investigator.
4. Anticipated continued use of neuraxial catheter after surgery.
5. Clinical laboratory findings at screening of thrombocytopenia or prolonged aPTT or PT such that anticoagulation is contraindicated according to the investigator
6. Uncontrolled hypertension according to the investigator.
7. Impaired liver function (transaminase >3 X ULN) or history of hepatic insufficiency.
8. Creatinine clearance <30 mL/min.
9. Antiplatelet agents other than low dose aspirin (< 200 mg).
10. The use of intermittent pneumatic compression.
11. Known hypersensitivity to contrast media or rivaroxaban.
12. Known drug or alcohol abuse.
13. Active malignant disease or current cytostatic treatment.
14. Stroke within the previous month.
15. Participation in an investigational drug study within the past 30 days or previous participation in this study.
16. Any condition that in the opinion of the investigator would put the subject at increased risk from participating in the study or expected inability to comply with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome is the composite of the occurrence of asymptomatic DVT as detected by bilateral venography and symptomatic VTE, i.e. DVT or fatal or non-fatal PE from randomisation to post-operative Day 35 inclusive.
The principle safety outcome is major bleeding or clinically relevant non-major bleeding from randomisation to post-operative Day 35 inclusive. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy outcome is the composite of the occurrence of asymptomatic DVT as detected by bilateral venography and symptomatic VTE, i.e., DVT or fatal or non-fatal PE, from
randomisation to post-operative Day 35 inclusive; VTE events for the primary analysis will be based on the adjudicated evaluation. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Outcomes are as follows:
- Objectively confirmed major VTE (proximal DVT, symptomatic DVT, PE, VTE related death) from randomisation to post-operative Day 35 inclusive
- Total DVT from randomisation to post-operative Day 35 inclusive
- Proximal DVT from randomisation to post-operative Day 35 inclusive
- Distal DVT from randomisation to post-operative Day 35 inclusive
- PE from randomisation to post-operative Day 35 inclusive
- VTE-related death from randomisation to post-operative Day 35 inclusive
- Objectively confirmed major VTE from randomisation to post-operative Day 70 inclusive |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Russian Federation |
Ukraine |
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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
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |