E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia A, a bleeding disorder caused by clotting fcator VIII deficiency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
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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 |
Primary Objectives: 1) To show the efficacy of desmopressin and FVIII concentrate combination treatment is equal to the efficacy of FVIII monotherapy 2) To show a reduction in FVIII concentrate consumption with desmopressin and FVIII concentrate combination treatment compared to FVIII monotherapy
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: a) To evaluate the safety of both treatment arms, i.e. occurrence of bleeding, dosing below target and other adverse events. b) To perform an economical evaluation to quantify the costs of combination treatment compared to standard treatment. c) To compare the proportion of patients with FVIII plasma levels within set target levels after the minor intervention. d) To evaluate experienced quality of care in participating patients. e) To evaluate discrepancies between one-stage and chromogenic FVIII-measurements before and after treatment with desmopressin. f) To evaluate the occurrence of FVIII inhibitors.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible for this study, a subject must meet all of the following criteria: - Non-severe hemophilia A patients (FVIII 0.01-0.40 IU/mL) - In need of a minor surgical intervention - Age minimally 12 and maximally 70 years at study inclusion date - Need for perioperative FVIII concentrates for a maximum of 48 hours - Having admissible results of a desmopressin test (see paragraph 3.1) - Absolute increase in FVIII 1 hour after desmopressin administration ≥ 0.2 IU/mL after a previous (test) dose - Male gender - (Parental) informed consent
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study: - Patients with other congenital or acquired hemostatic abnormalities - Clinically relevant FVIII inhibiting antibodies (>0.5 BU) preoperatively, unless successfully treated with immunotolerance therapy - Needed treatment duration with FVIII concentrates longer than 48 hours - Contraindications for desmopressin, e.g. cardiovascular disease (see appendix IV) - Use of co-medication that has an interaction with desmopressin (see appendix IV) - Intolerance to previous desmopressin administrations
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess our first main objective, efficacy of treatment is measured. Efficacy is defined as the average deviation of FVIII peak level to the predicted FVIII peak range in IU/mL in each treatment arm, without administering FVIII concentrate outside the dosing advice. The FVIII level for the primary endpoint is measured prior to the minor intervention, 10-15 minutes after the infusion of FVIII concentrate. The measurement for the primary endpoint is marked in appendix VIII. The deviation will be set to 0 for every FVIII measurement that falls into the predicted FVIII range. The predicted FVIII range will be set to the predicted peak level +/- 10%. Example: A patient has a target target trough FVIII value of 0.5 IU/mL after 24 hours. In order to keep the FVIII level above 0.5 IU/mL for the first 24 hours after the minor intervention, it is predicted the FVIII peak level will be as high as 1.10 IU/mL. The target range will then be set to 0.99-1.21 IU/mL. Predicted FVIII levels will never be lower than the FVIII target levels as described in paragraph 3.3 and 3.7. The FVIII concentrate consumption, our second main objective, will be evaluated as units per kilogram. Therefore, all units of administered FVIII concentrate and the body weight of each patient will be documented. The consumption of FVIII concentrate in units per kilogram will be calculated.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Both endpoints will be evaluated at the end of study. |
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E.5.2 | Secondary end point(s) |
a) Number and nature of bleeding during the first 14 days after the minor intervention (appendix VI) a) Other adverse events during the first 14 days after the minor intervention b) Treatment costs in both treatment arms c) The proportion of patients with FVIII plasma levels within set target levels after the minor intervention d) Experienced quality of care in participating patients e) Discrepancies between one-stage and chromogenic FVIII-measurements before and after desmopressin administration f) Inhibitor development 4-6 weeks after the minor intervention
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every endpoint will be evaluated at the end of study |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |