E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Antithrombin AT Deficient Patients in High-Risk Situations for Thrombosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020608 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess the incidence of thromboembolic events acute deep venous thrombosis DVT and/or thromboembolic events other than acute DVT following prophylactic intravenous IV administration of rhAT to patients with hereditary AT deficiency HD in situations usually associated with a high risk for thromboembolic events. |
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E.2.2 | Secondary objectives of the trial |
1.To assess the incidence of acute DVT following prophylactic IV administration of rhAT to patients with hereditary AT deficiency in situations usually associated with a high risk for thromboembolic events. 2.To assess the incidence of thromboembolic events other than acute DVT following prophylactic IV administration of rhAT to patients with hereditary AT deficiency in situations usually associated with a high risk for thromboembolic events. 3 To assess the safety, including the occurrence of anti-rhAT antibodies, in patients following treatment with rhAT. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion criteria require that study patients 1. Have HD with a personal history of venous thromboembolic events. 2. Have a history of HD that includes 2 or more plasma AT activity values 8804; 60 . 3. Be scheduled to have an elective procedure s known to be associated with a high risk for occurrence of a thromboembolic event. This will include non-pregnant surgical patients or pregnant patients scheduled for caesarean section or delivery induction. 4. Be at least 18 years of age, not exceeding 80 years of age. 5. Have signed an informed consent form. 6. Have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline. This applies only to female non-pregnant surgical patients of childbearing potential. 7. Are able to comply with the requirements of the study protocol. |
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E.4 | Principal exclusion criteria |
The following patients will be excluded from participating in the study 1. Patients who have a diagnosis of another hereditary thrombophilic disorder e.g., activated protein C APC resistance/Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation G20210A , or acquired lupus anticoagulant thrombophilic disorder . 2. Patients who have a baseline bilateral ultrasound positive for acute DVT or baseline diagnostic testing if required that is positive for a thromboembolic event other than acute DVT or have signs or symptoms of acute venous thrombosis at baseline 3. Patients who have a known allergy to goats or goat products. 4. Patients who have participated in a study employing a different investigational drug within 30 days of the start of their participation in the current trial. 5. Patients using fondaparinux sodium or the oral thrombin inhibitor, ximelagatran, or are expected to be treated with fondaparinux sodium or ximelagatran during the study period up to 7 days after stop of treatment . |
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E.5 End points |
E.5.1 | Primary end point(s) |
The first outcome assessment is a clinical diagnosis of the occurrence of acute DVT. An acute DVT will be considered to have occurred if, during rhAT treatment or within 7 days of discontinuation of treatment with rhAT 1. Clinical symptoms consistent with the occurrence of an acute DVT are present. Clinical symptoms of acute DVT can be calf pain, swelling/edema, redness, venous distention, or pain on dorsiflexion. AND 2. Confirmation of acute DVT is obtained by diagnostic imaging e.g., ultrasound, venography, computed tomography CT . The second outcome assessment is a clinical diagnosis of the occurrence of a thromboembolic event other than DVT e.g., pulmonary embolism . A thromboembolic event other than DVT will be considered to have occurred if, during rhAT treatment or within 7 days of discontinuation of treatment with rhAT 1. Clinical symptoms consistent with the occurrence of a thromboembolic event other than DVT are present. Clinical symptoms of thromboembolic events differ with the location, but shortness of breath, chest pain, headache, severe abdominal pain may all be indications of such event and warrant thorough investigation when these occur. AND 2. Confirmation of thromboembolic events other than DVT is obtained by diagnostic imaging e.g., ultrasound, angiography, CT, ventilation/perfusion scan . Because a treatment failure should be defined as the occurence of the outcome that a prophylactic agent should prevent, an rhAT treatment failure will be considered to have occurred when a thromboembolic event occurs during the treatment period and/or 7 days post treatment observation period |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 5 |
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 |