Physical Activity and FVIII Elimination: Relevance to Personalized Therapy in Severe Hemophilia A

Study Overview
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Brief Summary
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In persons with severe haemophilia A infused factor VIII half-life and other pharmacokinetic can vary according to determinants such as blood group, von Willebrand factor (VWF) level or age. However, FVIII pharmacokinetics (PK) has not been throughly studied in patients with severe HA as a function of daily physical activity. It si known that vigorous intensity physical activity/exercise can transiently but significantly increase circulating levels of endogenous VWF and consequently FVIII in normal subjects and in patients with moderate or mild haemophilia A. The proposed study is a Proof of Concept one as it will be aimed at investigating the relation between daily physical activity, measured by Sensewear armband device, as number of daily steps and PK variability of infused rec-FVIII concentrate. This kind of investigation has never been done and it is a great interest also for the evaluation of patient's qualitiy of life.

Detailed Description
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In persons with severe haemophilia A infused factor VIII half-life and other pharmacokinetic can vary according to determinants such as blood group, von Willebrand factor (VWF) level or age. However, FVIII pharmacokinetics (PK) has not been throughly studied in patients with severe HA as a function of daily physical activity. It si known that vigorous intensity physical activity/exercise can transiently but significantly increase circulating levels of endogenous VWF and consequently FVIII in normal subjects and in patients with moderate or mild haemophilia A. The proposed study is a Proof of Concept one as it will be aimed at investigating the relation between daily physical activity, measured by Sensewear armband device, as number of daily steps and PK variability of infused rec-FVIII concentrate. This kind of investigation has never been done and it is a great interest also for the evaluation of patient's qualitiy of life. Physical Examinations at screening and subsequent study visits a physical examination will be performed on the following body systems being described as normal or abnormal: general appearance, headand neck, eyes and ears, nose and throat, heart, abdomen, extremities and joints, lymph nodes and neurological. At screening, if an abnormal condition is detected, the condition will be described on the medical history CRF. At study visit, if a new abnormal or worsened abnormal pre-existing condition is detected, the condition will be described n the CRF.

Official Title
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Physical Activity and FVIII Elimination: Relevance to Personalized Therapy in Severe Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Device: SenseWear armband device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients 12-60 yo with severe HA under FVIII concentrates prophylaxis will be selected at the Haemostasis and Thrombosis Center of the Fondazione Policlinico Gemelli IRCCS Rome (FPG) Exclusion Criteria: all patients with malignant tumors or patietnts treated with anticoagulant / antiplatelet agents patients suffering from other congenital coagulation disorders (von Willebrand disease, other congenital deficiency of coagulation factors or severe thrombocytopenia (< 30,000 Plt/uL)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: patients with severe HA under FVIII concentrates prophylaxis<br>patients with severe HA under FVIII concentrates prophylaxis | Device: SenseWear armband device<br>* Device: SenseWear armband device Metabolic Holter, Physical Activity and Lifestyle, Portable outpatient multi-sensor energy consumption in calories (EE), movement, physical activity, quality of life<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study of the association between physical activity, measured by mean nuber of daily steps, with the Area Under the Curve (AUC) PK parameter in patients with severe HA under prophylaxis. | Study of the association between physical activity, measured by mean nuber of daily steps, with the Area Under the Curve (AUC) PK parameter in patients with severe HA under prophylaxis. Investigate whether and how the daily physical activity (measured as number of steps, using the SenseWear Armband device) affects the PK parameter. . | 12 months | 
| Association PK parameter and number of daily steps | In more details the study aims to evaluate whether and how the FVIII PK parameter is significantly associated with the mean number of daily steps in patients with severe HA | 12 months |