E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Antithrombin Deficient Patients in High risk Situations for Thrombosis. |
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MedDRA Classification |
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 |
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 ≤ 60% of normal. 3. Be scheduled to have an elective procedure(s) known to be associated with high risk for occurrence of DVT. 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 to exceed an age of 80 years. 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 |
Excluded patients include: 1. Patients who have a diagnosis of Protein S or C 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).
In addition, hospitalized pregnant HD patients in active labor and eligible HD patients previously treated with rhAT will be allowed entry into the study. |
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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, 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 event 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 occurrence 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-day 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 | No |
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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
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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Patients will be enrolled into the study until there are 17 evaluable patients. An evaluable patient is a patient who has been treated with rhAT and had at least a 7-day post end of treatment evaluation. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |