An Observational Study to Evaluate Physical Activity, Bleeding Incidence and Health Related Quality of Life, in Participants With Haemophilia A Without Inhibitors Receiving Standard of Care Treatment (POWER)

A Multicenter, Non-Interventional Study to Evaluate Physical Activity, Bleeding Incidence and Health Related Quality of Life, in Patients With Haemophilia A Without Inhibitors Receiving Standard of Care Treatment

This multicenter, non-interventional, prospective study will collect information about activity status, bleeds, health-related quality of life (HRQoL), health status, and safety in participants with moderate or severe haemophilia A without factor VIII (FVIII) inhibitors, who are being treated in accordance with normal clinical practice.

Study Overview

• Status: Completed
• Conditions: Haemophilia A; Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor; Severe Hereditary Factor VIII Deficiency Disease Without Inhibitor
• Intervention / Treatment: Drug: Standard of Care for Haemophilia A

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Az. Osp. Pugliese Ciaccio; S. C. Emofilia, Emostasi e Trombosi
  • Campania
    • Napoli, Campania, Italy, 80131
      • AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia
  • Emilia-Romagna
    • Cesena, Emilia-Romagna, Italy, 47521
      • PO Cesena - Osp M. Bufalini; Patologia Clinica - S.S.A. Serv. Medicina Trasf.- Centro Emofilia
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
    • Roma, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù; Oncoematologia Centro Emostasi e Trombosi
    • Roma, Lazio, Italy, 00168
      • Policlinico Univ. A. Gemelli; Polo di Scienze Oncologiche ed Ematologiche
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"
    • Pavia, Lombardia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo; S.C. Medicina Generale 2 - Centro Emofilia
  • Piemonte
    • Alessandria, Piemonte, Italy, 15100
      • A.O.Santi Antonio e Biagio e Cesare Arrigo; S.S. Emostasi e Trombosi - Dip. Onco-Ema e Med Spec.
    • Torino, Piemonte, Italy, 10126
      • AO Città Salute e Scienza D-Osp S. G. Battista Molinette; SSCVD Malattie Tromboti e Emorragiche
    • Torino, Piemonte, Italy, 10126
      • Osp. Infant. Regina Margherita; S.S.D. Medicina Trasfusionale Materno-infantile Traumatologica
  • Puglia
    • Bari, Puglia, Italy, 70124
      • AOU Cons. Policlinico Bari; Centro Emofilia e Trombosi - UO Medicina Trasfusionale
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
    • Via S. Sofia 78, Sicilia, Italy, 95123
      • Ospedale Ferrarotto; Divisione Di Ematologia
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • AOU Careggi; SOD Malattie Emorragiche
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova; Centro Emofilia
    • Vicenza, Veneto, Italy, 36100
      • Ospedale Di Vicenza; Nefrologia, Ematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Approximately 150 participants overall, 125 with severe haemophilia A and 25 with moderate haemophilia A without inhibitors against factor VIII (FVIII), are planned to be enrolled at sites across Italy.

Description

Inclusion Criteria:

• Must own a device compatible with the electronic Patient-Reported Outcome (ePRO) application and with the fitness tracker that will be provided to the patient
• Must have on his/her own device a data traffic availability of at least 2 gigabytes (GB) in total per month intended only for use of study applications and data transfer. If the data traffic plan is exhausted, the participant must be able to connect to a wi-fi network at least once every day in order to transfer the data collected for the study purpose
• Must accept to run on his/her own device the ePRO application and the fitness tracker application
• Must be available to turn on daily the bluetooth connection of his/her own device in order to allow the synchronization with the fitness tracker
• Ability and willingness to comply with all aspects of the protocol, including completion of questions on the ePRO application (for underage population, ePRO questions can be answered by legally authorized representative if deemed necessary)
• Ability and willingness to wear the activity tracking device as indicated
• Diagnosis of severe (FVIII <1%) or moderate (FVIII ≥1% and ≤2%) congenital haemophilia A
• No prior history of a positive inhibitor against FVIII. If participant has a previous history of inhibitor development, the participant must have successfully eradicated inhibitors since 3 years.
• At least 150 exposure days of FVIII prior to enrolment

Exclusion Criteria:

• Bleeding disorder other than congenital haemophilia A
• Ongoing (or planned during the study) immune tolerance induction or FVIII prophylaxis if the participant has currently low titre of inhibitors or had inhibitors in the past 3 years
• Previous or concomitant autoimmune or connective tissue disease
• History of or suspected allergy or intolerance to any of the component of the fitness device (e.g., aluminium anodised)
• History of clinically significant hypersensitivity associated with monoclonal antibody
• Obesity (Body Mass Index [BMI] ≥30 kilograms/metre squared of body surface area [kg/m^2})
• Clinically important cardiovascular, metabolic, endocrine disorders or any other concomitant diseases or conditions that could limit the mobility of participant or could represent any risk according to the Investigator's judgment, or that could interfere with the study evaluation parameters
• Participation in any other interventional clinical trial, including Roche sponsored studies or in any other support program that may include drug administration other than standard clinical practice (e.g., compassionate use, use not in agreement with the authorized indications, patient support programs, etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Haemophilia A Without FVIII Inhibitors	Drug: Standard of Care for Haemophilia A; There is no pre-determined studied medicinal product. Any treatment (including treatments started during the observational period) will be administered according to standard clinical practice, independently of participation in the current study, according to clinician's independent therapeutic decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Daily Active Minutes of Physical Activity Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	Physical activity data was collected as daily active minutes measured on each valid day by wearing a fitness tracker continuously during study participation. Valid day = a day in which fitness tracker was worn for at least 10 hours. Daily active minutes were saved in two different sets of data collected by fitness tracker. For each set minutes were categorized by intensity of activity done. First set = minutes categorized according to time collected in each heart zone. Overall heart zone minutes = fat-burn minutes (heart rate: 50-69% of maximum) + cardio minutes (medium-to-high intensity exercise zone corresponds to heart rate: 70-84% of maximum) + peak minutes (high-intensity exercise zone, corresponds to heart rate > 85% of maximum). Second set =minutes categorized according to active zones. Overall active zone minutes=lightly active minutes +fairly active minutes+very active minutes. Moderate-to-Vigorous Physical Activity (MVPA) minutes=Fairly active minutes+Very active minutes.	From baseline to study completion (up to 18 months)
Mean Number of Steps Taken Per Day by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	Number of steps taken by the participants on each valid day were measured by wearing a fitness tracker continuously during study participation. Valid day was defined as a day in which fitness tracker was worn for at least 10 hours.	From baseline to study completion (up to 18 months)
Mean Metabolic Equivalent of Tasks (METs) Per Day Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	The MET is an objective measure of the ratio of the rate at which a person expends energy, relative to the mass of that person, while performing some specific physical activity compared to a reference. The METs were derived as: (amount of kilo calories (kcal) collected in the fat-burn, cardio, and peak minutes) / [(sum of fat-burn, cardio and peak hours) * weight of the participant in kilograms (kg)].	From baseline to study completion (up to 18 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of Possible Early Retirement of Caregiver, as Reported by Caregivers in a Questionnaire		Baseline and every month until study completion (up to 18 months)
Mean Rate of the Number of Times Engaging in Physical Activity Per Week by Type of Physical Activity Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	The activity weekly rate was derived on a per participant basis as ratio between the number of times that the type of activity is reported on the fitness tracker (numerator) and the length of the observational period (i.e. end of study date - baseline date + 1) (denominator) and then multiplied by 7. The physical activities were categorized in the following groups: exercises at intervals, gym weights, running, swimming, tapis roulant, walk, general exercises: other types of physical activity identified by the fitness tracker that are not already included in the above-mentioned categories.	From baseline to study completion (up to 18 months)
Mean Active Minutes by Intensity (Lightly Active Minutes) for Each Type of Physical Activity Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	The number of active minutes by intensity (lightly, fairly, and very active minutes) were obtained at the participant level on a per activity basis as the median of the values collected by the fitness tracker for each activity recorded during the observational period. In this analysis, the means and 95% confidence intervals were calculated using the median lightly active minutes by type of physical activity performed by participants with available data. The physical activities were categorized in the following groups: exercises at intervals, gym weights, running, swimming, tapis roulant, walk, general exercises: other types of physical activity identified by the fitness tracker that are not already included in the above-mentioned categories.	From baseline to study completion (up to 18 months)
Mean Active Minutes by Intensity (Fairly Active Minutes) for Each Type of Physical Activity Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	The number of active minutes by intensity (lightly, fairly, and very active minutes) were obtained at the participant level on a per activity basis as the median of the values collected by the fitness tracker for each activity recorded during the observational period. In this analysis, the means and 95% confidence intervals were calculated using the median fairly active minutes by type of physical activity performed by participants with available data. The physical activities were categorized in the following groups: exercises at intervals, gym weights, running, swimming, tapis roulant, walk, general exercises: other types of physical activity identified by the fitness tracker that are not already included in the above-mentioned categories.	From baseline to study completion (up to 18 months)
Mean Active Minutes by Intensity (MVPA Minutes) for Each Type of Physical Activity Performed by Participants (by Age Categories: 12-17, 18-30, and 31-50 Years) Over the Course of the Study	The number of active minutes by intensity (lightly, fairly, and very active minutes) were obtained at the participant level on a per activity basis as the median of the values collected by the fitness tracker for each activity recorded during the observational period. The MVPA minutes is the sum of fairly active and very active minutes. In this analysis, the means and 95% confidence intervals were calculated using the median MVPA minutes by type of physical activity performed by participants with available data. The physical activities were categorized in the following groups: exercises at intervals, gym weights, running, swimming, tapis roulant, walk, general exercises: other types of physical activity identified by the fitness tracker that are not already included in the above-mentioned categories.	From baseline to study completion (up to 18 months)
Percentage of Participants Who Were Adherent to World Health Organization (WHO) Global Recommendations on Physical Activity for Health Over the Course of the Study	A participant was defined "adherent" to WHO guidelines according to the following algorithm: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). A participant who was adherent to the WHO guidelines according to the above definition was defined as an "active participant", otherwise as a "sedentary participant".	From baseline to study completion (up to 18 months)
Number of Participants by the Presence of Bleeds (0 vs. ≥1 Bleeds) Over the Course of the Study, Reported Via the ePRO Application	Bleeds that occurred the same day but in different body site were counted separately.	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Participants by the Presence of Bleeds (0 vs. ≥1 Bleeds) Over the Course of the Study According to the Different Types of Bleeds (Spontaneous, Traumatic and Procedure/Surgery Related), Reported Via the ePRO Application	The assessment of bleeds was divided into spontaneous bleeds, traumatic bleeds, and bleeds related to procedure/surgery. Spontaneous bleeds = the occurrence of hemorrhage where neither the participant nor a caregiver could identify a reason. Traumatic bleeds = hemorrhage occurring secondary to an event such as trauma, "strenuous" activity, or "overuse". Bleeds related to procedure/surgery = such as hematomas resulting from any surgeries or invasive procedures.	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months).
Number of Participants by the Presence of Bleeds (0 vs. ≥1 Bleeds) Over the Course of the Study According to the Bleed Sites (Urine, Feces, and Vomit, Joint, Muscle, and Other Bleeds), Reported Via the ePRO Application	Sites of bleeds were defined as urine, faeces, and vomit (three sites grouped together), joint, muscle, and other bleeds.	Baseline and whenever bleeding occured from study initiation to completion (up to 18 months)
Number of Participants by the Type of Regimen Used for Treatment of Haemophilia A Over the Course of the Study	The following types of regimens used to treat haemophilia A are reported here: on-demand (to stop bleeding) and prophylaxis (regular infusions of clotting factor to prevent bleeds). Participants could have received more than one medication.	From baseline to study completion (up to 18 months)
Number of Participants by the Product Used for Treatment of Haemophilia A Over the Course of the Study	Participants could have received more than one medication.	From baseline to study completion (up to 18 months)
Number of Participants Who Switched to a New Approved Drug for Treatment of Haemophilia A by the Product Used	Participants could have received more than one medication.	From baseline to the time of switch to a new therapy (up to 18 months)
Number of Treated Bleeds Over the Course of the Study	An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.).	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Bleeds Treated With Each Type of Treatment for Bleeding (Haemostatic Treatment, Treatment for Pain)	An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.).	From baseline to whenever bleeding occurred (up to 18 months)
Duration of Treatment for Bleeding Over the Course of the Study		Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Bleeds Treated With Each Route of Administration Over the Course of the Study	Number of bleeds treated by intravenous, subcutaneous, intramuscular, nasal, ophthalmic, oral, rectal, and other routes of administration are reported here.	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Bleeds Which Needed to Receive a Transfusion		Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Bleeds Which Needed to Administer an Additional Hemostatic Therapy		Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Bleeds With Adherence to Treatment Regimen for Haemophilia A in the Week Preceding the Bleeding	The adherence to the treatment regimen for haemophilia A was analyzed as the number of bleeds with an answer equal to "Yes" and "My therapeutic plan does not include any treatment in the last week" in the week preceding the bleeding.	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Number of Participants Who Were Adherent to the Treatment Regimen for Haemophilia A Over the Course of the Study by Adherence Category (<80% vs. ≥80% of Study Weeks)	The adherence to the treatment regimen for haemophilia A was analyzed as the number of participants with <80% or ≥80% of weeks on study with "Yes" and "My therapeutic plan does not include any treatment in the last week" over the total number of weeks reported via the ePRO. Missing data from some weeks was treated as "No". The total number of weeks on study for each participant was derived as (End of study date - Baseline date + 1) / 7.	From baseline to study completion (up to 18 months)
Number of Participants by the Product of Concomitant Medications Taken to Control Pain Over the Course of the Study	Participants could have received more than one medication.	Baseline and every 3 months until study completion (up to 18 months)
Pain Intensity, as Reported by Participants Using a Visual Analogue Scale	Participants reported the intensity of pain in their main joints (elbow, knee, ankle) by marking on a visual analogue scale (VAS), a horizontal line 100 millimeters (mm) in length, anchored by word descriptors at each end, where the left extreme means "No pain = 0" while the right extreme means "Worst Pain Imaginable = 100". The VAS score is the distance (in mm) from the left end of the line to the point where the participant marks crossed the line. VAS scale was submitted to the participants every month during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Health-Related Quality of Life (HRQoL): European Quality of Life-5 Dimensions (EQ-5D-5L) Health State Utility Index Score Over Time	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L includes five levels of severity in each of the five EuroQol-5D dimensions and the EQ VAS. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension having 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Response options are measured with a 5-point Likert scale. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state. EQ-5D-5L questionnaire was submitted to the participants every 3 month from baseline during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Health Status Measured Over Time, as Reported by Participants Using EQ-5D VAS Score	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and the other section is an evaluation of the overall health status using VAS. The VAS records the respondent's self-rated health on a 20 centimeter (cm) vertical VAS from 0 to 100 on how good or bad their health is at assessment; 0 means the worst health imaginable, and 100 means the best health imaginable.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Haemophilia Joint Health Score (HJHS) Total Score Over Time	The HJHS is an instrument developed to measure joint health status and to identify early signs of joint disease in children. This tool assesses joints most commonly affected by bleeding (knees, ankles, and elbows). Each of the 6 joints is assessed across 8 domains (Swelling, Duration of Swelling, Atrophy, Crepitus, Flexion Loss, Extension Loss, Pain, and Strength), and a Total Score is calculated as the sum of all joint domain scores. The score range is from 0 to 124 points (a score of 0 indicates no joint damage). A higher score indicates higher joint damage.	Baseline, Months 6 and 12
Mean Body Mass Index (BMI) Over Time		Baseline, Months 3, 6, 9, 12, 15 and 18
Yearly Rate of Days Away From School or Work for Participants	The number of days away from school or work (participant) was analyzed every month as a continuous variable. The yearly rate was derived on a per participant basis as the proportion between the total number of days away from school and/or work and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Days Away From Work for Parent/Caregiver	The number of days away from work was analyzed every month as a continuous variable. The yearly rate was derived on a per participant (for parents and caregivers) basis as the proportion between the total number of days away from work and duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Hospitalization Days	The yearly rate was derived on a per participant basis as the proportion between the total number of hospitalization days and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Number of Active Versus Sedentary Participants by the Severity (Moderate or Severe) of Haemophilia A	Participants who were adherent to the WHO guidelines for physical activity according to the below definition were defined as an "active participant", otherwise as a "sedentary participant". A participant was defined "adherent" to WHO guidelines according to the following algorithm: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). The participants were classified as 'Active' or 'Sedentary' based on data collected from baseline till the end of the study.	From baseline up to study completion (up to 18 months)
Annualized Bleeding Rates (ABR) in Active Versus Sedentary Participants	The annualized bleeding rate was derived as follows: total number of bleeds/total follow-up (person-year), where the individual's study duration was given by ([end of study date-baseline date +1] divided by 365.25). ABR was reported in active and sedentary participants. A participant who was adherent to the WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes).	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Pain Intensity in Active Versus Sedentary Participants, as Reported by Participants Using a Visual Analogue Scale	Participants reported intensity of pain in their main joints (elbow, knee, ankle) by marking on a VAS, a horizontal line 100 mm in length, anchored by word descriptors at each end, where the left extreme means "No pain = 0" while right extreme means "Worst Pain Imaginable = 100". VAS score is the distance (in mm) from left end of the line to the point where participant marks crossed the line. A participant who was adherent to WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day ≥60 minutes. 18-50 years old: Fairly active (moderate) minutes per week ≥150 minutes or Very active (vigorous) minutes per week ≥75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). VAS scale was submitted to the participants every month during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Number of Active Versus Sedentary Participants by the Product of Concomitant Medications Taken to Control Pain Over the Course of the Study	A participant who was adherent to the WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). Participants can have received more than one medication.	Baseline and every 3 months until study completion (up to 18 months)
Number of Active Versus Sedentary Participants by the Type of Regimen Used for Treatment of Haemophilia A Over the Course of the Study	The following types of regimens used to treat haemophilia A are reported here: on-demand (to stop bleeding) and prophylaxis (regular infusions of clotting factor to prevent bleeds). A participant who was adherent to the WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes). Participants can have received more than one medication.	From baseline to study completion (up to 18 months)
Number of Active Versus Sedentary Participants by the Product Used for Treatment of Haemophilia A Over the Course of the Study	A participant who was adherent to the WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes).	From baseline to study completion (up to 18 months)
Number of Active Versus Sedentary Participants Who Switched to a New Approved Drug for Treatment of Haemophilia A by the Product Used	A participant who was adherent to the WHO guidelines for physical activity according to the below definition was defined as an "active participant", otherwise as a "sedentary participant". WHO guidelines for adherence: 12-17 years old: MVPA minutes per day >= 60 minutes. 18-50 years old: Fairly active (moderate) minutes per week >= 150 minutes or Very active (vigorous) minutes per week >= 75 minutes or an equivalent combination of fairly and very active minutes (i.e., considering 1 fairly active minute as 0.5 very active minutes).	From baseline to the time of switch to a new therapy (up to 18 months)
HRQoL: EQ-5D-5L Health State Utility Index Score Over Time for Active Versus Sedentary Participants	EQ-5D-5L is a standardized measure of health status developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L includes five levels of severity in each of five EuroQol-5D dimensions and EQ VAS. Descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension having 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Response options are measured with a 5-point Likert scale. 5D-5L systems are converted into a single index utility score between 0-1, where higher score indicates a better health state and lower score indicate worse health state. A participant who was adherent to WHO guidelines for physical activity was defined as an "active participant", otherwise as a "sedentary participant". EQ-5D-5L questionnaire was submitted to participants every 3 month from baseline during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Health Status Measured Over Time, as Reported by Participants Using EQ-5D VAS Score in Active Versus Sedentary Participants	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities pain/discomfort, anxiety/depression) and the other section is an evaluation of the overall health status using VAS. The VAS records the respondent's self-rated health on a 20 centimeter (cm) vertical VAS from 0 to 100 on how good or bad their health is at assessment; 0 means the worst health imaginable, and 100 means the best health imaginable. A participant who was adherent to the WHO guidelines for physical activity was defined as an "active participant", otherwise as a "sedentary participant".	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
HJHS Total Score for Active Versus Sedentary Participants Over Time	The HJHS is an instrument developed to measure joint health status and to identify early signs of joint disease in children. This tool assesses joints most commonly affected by bleeding (knees, ankles, and elbows). Each of the 6 joints is assessed across 8 domains (Swelling, Duration of Swelling, Atrophy, Crepitus, Flexion Loss, Extension Loss, Pain, and Strength), and a Total Score is calculated as the sum of all joint domain scores. The score range is from 0 to 124 points (a score of 0 indicates no joint damage). A higher score indicates higher joint damage.	Baseline, Months 6 and 12
Yearly Rate of Number of Days Away From School/Work for Active Versus Sedentary Participants	The number of days away from school or work (participant) was analyzed every month as a continuous variable. The yearly rate was derived on a per participant basis as the proportion between the total number of days away from school and/or work and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Number of Days Away From Work for Active Versus Sedentary Participant's Parents or Caregivers	The number of days away from work was analyzed every month as a continuous variable. The yearly rate was derived on a per participant (for parents/caregivers) basis as the proportion between the total number of days away from work and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Number of Hospitalization Days for Active Versus Sedentary Participants	The yearly rate was derived on a per participant basis as the proportion between the total number of hospitalization days and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Annualized Bleeding Rates in Active Versus Sedentary Participants by the Severity (Moderate Versus Severe) of Haemophilia A	The annualized bleeding rate was derived as follows: total number of bleeds/total follow-up (person-year), where the individual's study duration was given by ([end of study date-baseline date +1] divided by 365.25). A participant who was adherent to the WHO guidelines for physical activity was defined as an "active participant", otherwise as a "sedentary participant". Participants were classified for disease severity at baseline: severe (Factor VIII activity <1%) or moderate (Factor VIII activity between ≥1% and ≤2%) haemophilia A.	Baseline and whenever bleeding occurred from study initiation to completion (up to 18 months)
Pain Intensity in Participants With Moderate Versus Severe Haemophilia A, as Reported by Participants Using a Visual Analogue Scale	Participants reported the intensity of pain in their main joints (elbow, knee, ankle) by marking on a VAS, a horizontal line 100 mm in length, anchored by word descriptors at each end, where the left extreme means "No pain = 0" while the right extreme means "Worst Pain Imaginable = 100". The VAS score is the distance (in mm) from the left end of the line to the point where the participant marks crossed the line. VAS scale was submitted to the participants every month during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 18
Number of Participants With Moderate Versus Severe Haemophilia A by the Product of Concomitant Medications Taken to Control Pain Over the Course of the Study	Participants could have received more than one medication.	Baseline and every 3 months until study completion (up to 18 months)
Number of Participants With Moderate Versus Severe Haemophilia A by the Type of Regimen Used for Treatment of Haemophilia A Over the Course of the Study	The following types of regimens used to treat haemophilia A are reported here: on-demand (to stop bleeding) and prophylaxis (regular infusions of clotting factor to prevent bleeds). Participants could have received more than one medication.	From baseline to study completion (up to 18 months)
Number of Participants With Moderate Versus Severe Haemophilia A by the Product Used for Treatment of Haemophilia A	Participants could have received more than one medication.	From baseline to study completion (up to 18 months)
Number of Participants With Moderate Versus Severe Haemophilia A Who Switched to a New Approved Drug for Treatment of Haemophilia A by the Product Used	Participants could have received more than one medication.	From baseline to the time of switch to a new therapy (up to 18 months)
HRQoL: EQ-5D-5L Health State Utility Index Score Over Time Moderate Versus Severe Haemophilia A	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L includes five levels of severity in each of the five EuroQol-5D dimensions and the EQ VAS. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each dimension having 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Response options are measured with a 5-point Likert scale. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state. EQ-5D-5L questionnaire was submitted to the participants every 3 month from baseline during the study.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Health Status Measured Over Time, as Reported by Participants Using EQ-5D VAS Score in Participants With Moderate Versus Severe Haemophilia A	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and the other section is an evaluation of the overall health status using VAS. The VAS records the respondent's self-rated health on a 20 cm vertical VAS from 0 to 100 on how good or bad their health is at assessment; 0 means the worst health imaginable, and 100 means the best health imaginable.	Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
HJHS Total Score for Participants With Moderate Versus Severe Haemophilia A	The HJHS is an instrument developed to measure joint health status and to identify early signs of joint disease in children. This tool assesses joints most commonly affected by bleeding (knees, ankles, and elbows). Each of the 6 joints is assessed across 8 domains (Swelling, Duration of Swelling, Atrophy, Crepitus, Flexion Loss, Extension Loss, Pain, and Strength), and a Total Score is calculated as the sum of all joint domain scores. The total score range is from 0 to 124 points (a score of 0 indicates no joint damage). A higher score indicates higher joint damage.	Baseline, Months 6 and 12
Yearly Rate of Days Away From School for Participants With Moderate Versus Severe Haemophilia A	The number of days away from school or work (participant) was analyzed every month as a continuous variable. The yearly rate was derived on a per participant basis as the proportion between the total number of days away from school and/or work and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Days Away From Work for Parents/Caregivers of Participants With Moderate Versus Severe Haemophilia A	The number of days away from work was analyzed every month as a continuous variable. The yearly rate was derived on a per participant (for parents/caregivers) basis as the proportion between the total number of days away from work and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)
Yearly Rate of Hospitalization Days for Participants With Moderate Versus Severe Haemophilia A	The yearly rate was derived on a per participant basis as the proportion between the total number of hospitalization days and the duration of the study (derived as end of study date - baseline date + 1) multiplied by 365.25.	Baseline and every month until study completion (up to 18 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Petracca F, Tempre R, Cucciniello M, Ciani O, Pompeo E, Sannino L, Lovato V, Castaman G, Ghirardini A, Tarricone R. An Electronic Patient-Reported Outcome Mobile App for Data Collection in Type A Hemophilia: Design and Usability Study. JMIR Form Res. 2021 Dec 1;5(12):e25071. doi: 10.2196/25071.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: November 13, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Factor VIII; Hemophilia A
• Additional Relevant MeSH Terms: Hematologic Diseases; Nutrition Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Malnutrition; Blood Coagulation Disorders; Hemophilia A; Deficiency Diseases; Coagulants; Factor VIII
• Other Study ID Numbers: ML40983

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No