Covid 19 Research using Clinical Trials (Home Page)
ADYNOVIWiki
Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation
Correlated HPO Terms (1)
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0003125 | Reduced factor VIII activity HPO | 0.50 |
There is one clinical trial.
Clinical Trials
1 ADVATE/ ADYNOVI Hemophilia A Outcome Database
The purpose of the study is to document the natural history of hemophilia A disease and long-term outcomes in terms of effectiveness, safety and quality of life in participants receiving Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) or Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG) in routine clinical practice
NCT02078427 Hemophilia A Biological: ADVATE Biological: ADYNOVI MeSH:Hemophilia A
HPO:Reduced factor VIII activity
Primary Outcomes
Description: The World Federation of Hemophilia developed a musculoskeletal evaluation system, commonly referred to as the Gilbert test, to measure hemophilia joint health status.The Gilbert test needs to be performed in the absence of acute bleed, acute pain, and acute inflammation into the evaluated joint. Four parameters are used in each Gilbert test: pain (score: 0-3), bleeding (score: 0-3), physical exam (score: 0-12), and X-ray evaluation (score: 0-13) Scores of 0, represent no pain, no bleeding, no physical exam issues, and/or no x-ray issues. Higher scores for each of these categories represents worsening conditions.
Measure: Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale Time: Up to approximately 12 years
Secondary Outcomes
Description: The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized Bleed Rate, All Joints Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized Bleed Rate, All Bleeds Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized bleed rate, pre-existing target joints at baseline Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: The incidence of new target joints will be calculated as the total number of new target joints in all participants divided by the total number of observation days.
Measure: Incidence of New Target Joints Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: The status of joint health by X-ray by Pettersson score will be summarized for each observational year.
Measure: Status of joint health by X-ray by Pettersson scale Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit.
Description: LSS score format= A(e:s:h). Sum of values for Subchondral Cyst (score: 1-6), irregularity/erosion of Subchondral Cortex (score: 1-4), and Chondral Destruction (score: 1-6) gives value for the A component of score. e, s, h components represent effusion/hemarthrosis, hypertrophic synovial, & hemosiderin deposition (score: 0-4 for each). Max. score is 16(4:4:4).
Subchondral Cyst:
≥1 bone
≥2 bones
>3 cysts in ≥1 bone
>3 cysts ≥2 bones
Largest size >4 mm: ≥1 bone
Largest size >4 mm: ≥2 bones
Subchondral Cortex
≥1 bone
≥2 bones
Involve > half joint surface: ≥1 bone
Involve > half of joint surface: ≥2 bones
Chondral Destruction
≥1 bone
≥2 bones
Full thickness defect (FTD): ≥1 bone
FTD: ≥2 bones
FTD involves >1/3 of joint surface: ≥1 bone
FTD involves >1/3 of joint surface: ≥2 bones
Effusion/hemarthrosis (e): Hypertrophic synovial (s): Hemosiderin (h): (0-4 for each):
0 absent
1 equivocal
2 small
3 moderate
4 large
Measure: Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: The International Prophylaxis Study Group (IPSG) developed a scoring system for musculoskeletal evaluation, the HJHS, optimized for use in children with no or minimal joint disease.
The HJHS includes the following parameters: swelling, duration of swelling, muscle atrophy, joint pain, crepitus on motion, flexion loss, extension loss, strength and global gait.
Measure: Status of joint health using the Hemophilia Joint Health Score (HJHS) Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with prior prophylaxis; if participant did not receive prior prophylaxis with rAHF-PFM, rAHF-PEG or other Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation
Good: Minor increase in BBR within last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, slightly less than expected outcome according to investigator's expectation
Fair: Moderate increase in BBR in last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, somewhat less than expected outcome according to investigator's expectation
Poor: Significant increase in BBR in the 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, little to no benefit according to investigator's expectation
Measure: Overall effectiveness assessment for prophylaxis therapy Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Evaluation of patients´ compliance to prescribed prophylactic treatment will be performed by the treating physician. Compliance will be categorized according to a 4-point table (Highly compliant, Fairly compliant, Moderately compliant, Poorly compliant)
Measure: Compliance with the dosing prescribed and its relationship with effectiveness Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Excellent: Bleed episodes typically respond to same or fewer number of infusion and same or lower dose as compared with previous on-demand treatment or investigator's expectation
Good: Most bleed episodes typically respond to same number of infusion and dose but some require more infusions or higher dose as compared with previous on-demand treatment or investigator's expectation
Fair: Bleed episodes typically require more infusions and/or higher dose than expected as compared with previous on-demand treatment or investigator's expectation
Poor: Bleed episodes routinely fail to respond to same number of infusion and dose and require additional or different factor concentrate for hemostatic control as compared with previous on-demand treatment or investigator's expectation
Measure: Overall effectiveness assessment for on-demand treatment Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Excellent: Full relief of pain and cessation of bleeding as evidenced by objective signs (e.g., swelling, tenderness, irritability, inconsolability, and decreased range of motion in the case of musculoskeletal hemorrhage) within approximately 8 hours of a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring.
Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after the infusion. Possibly requires more than 1 infusion for complete resolution.
Fair: Probable or slight relief of pain and slight improvement in signs of bleeding within approximately 8 hours after the infusion. Requires more than 1 infusion for complete resolution.
Poor: No improvement or condition worsens.
Measure: Global effectiveness assessment for on-demand treatment Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Measure: Number of rAHF-PFM or rAHF-PEG units required for bleed cessation Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Description: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Measure: Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Measure: Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Measure: Incidence of pseudo tumor development Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The the lHAL measures activities involving the upper extremities, basic activities involving ower extremities and complex activities involving the lower extremities as well as an overall physical activity score for adults.
Measure: Quality of Life: HAL questionnaire - for adult patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The SF-12v2 measures generic health-related quality of life for adults.
Measure: Quality of Life: SF-12v2 questionnaire - for adult patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The EQ-5D measures health utility in adult participants.
Measure: Quality of Life: EQ-5D questionnaire - for adult patients Time: Enrollment visit;Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The PedHAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for children.
For participants 4-13 years of age:
- PedHAL (parent version)
For participants 14-17 years of age:
- PedHAL (child version)
Measure: Quality of Life: PedHAL questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The SF-10 measures generic health-related quality of life for children and is parent-completed.
Measure: Quality of Life: SF-10 questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The EQ-5D measures health utility in subjects aged 14 and up.
Measure: Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).
During screening visit and on an annual basis, the investigators shall ask participants to rate the average level of chronic pain associated with hemophilia over the period of 4 weeks prior to visit date using the VAS.
Measure: Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).
Participants will be asked to provide ratings on level of acute pain associated with each bleeding episode using the VAS. The VAS scores will be recorded in the participant diary.
Measure: Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Measure: Number of days lost from school or work due to bleeding episodes Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG
Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 1 Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: Difference in number of weekly doses between previous regimen and rAHFPEG
Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 2 Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels Lesser than (<)1%, Lesser Than or Equal to (<=) 2%, and <= 5% without history of inhibitor Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of therapy-related serious adverse events Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of therapy-related non-serious adverse events Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Description: Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients
Measure: Incidence of inhibitors after switching to rAHF-PEG Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Related HPO nodes (Using clinical trials)
Primary Outcomes
Description: The World Federation of Hemophilia developed a musculoskeletal evaluation system, commonly referred to as the Gilbert test, to measure hemophilia joint health status.The Gilbert test needs to be performed in the absence of acute bleed, acute pain, and acute inflammation into the evaluated joint. Four parameters are used in each Gilbert test: pain (score: 0-3), bleeding (score: 0-3), physical exam (score: 0-12), and X-ray evaluation (score: 0-13) Scores of 0, represent no pain, no bleeding, no physical exam issues, and/or no x-ray issues. Higher scores for each of these categories represents worsening conditions.
Measure: Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale Time: Up to approximately 12 yearsSecondary Outcomes
Description: The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized Bleed Rate, All Joints Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized Bleed Rate, All Bleeds Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants with a minimum observation period of 90 days per treatment regimen.
Measure: Annualized bleed rate, pre-existing target joints at baseline Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: The incidence of new target joints will be calculated as the total number of new target joints in all participants divided by the total number of observation days.
Measure: Incidence of New Target Joints Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: The status of joint health by X-ray by Pettersson score will be summarized for each observational year.
Measure: Status of joint health by X-ray by Pettersson scale Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit.Description: LSS score format= A(e:s:h). Sum of values for Subchondral Cyst (score: 1-6), irregularity/erosion of Subchondral Cortex (score: 1-4), and Chondral Destruction (score: 1-6) gives value for the A component of score. e, s, h components represent effusion/hemarthrosis, hypertrophic synovial, & hemosiderin deposition (score: 0-4 for each). Max. score is 16(4:4:4). Subchondral Cyst: ≥1 bone ≥2 bones >3 cysts in ≥1 bone >3 cysts ≥2 bones Largest size >4 mm: ≥1 bone Largest size >4 mm: ≥2 bones Subchondral Cortex ≥1 bone ≥2 bones Involve > half joint surface: ≥1 bone Involve > half of joint surface: ≥2 bones Chondral Destruction ≥1 bone ≥2 bones Full thickness defect (FTD): ≥1 bone FTD: ≥2 bones FTD involves >1/3 of joint surface: ≥1 bone FTD involves >1/3 of joint surface: ≥2 bones Effusion/hemarthrosis (e): Hypertrophic synovial (s): Hemosiderin (h): (0-4 for each): 0 absent 1 equivocal 2 small 3 moderate 4 large
Measure: Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: The International Prophylaxis Study Group (IPSG) developed a scoring system for musculoskeletal evaluation, the HJHS, optimized for use in children with no or minimal joint disease. The HJHS includes the following parameters: swelling, duration of swelling, muscle atrophy, joint pain, crepitus on motion, flexion loss, extension loss, strength and global gait.
Measure: Status of joint health using the Hemophilia Joint Health Score (HJHS) Time: Screening visit; Annual/Interval visits:- Up to 8 years if rAHF-PFM alone- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with prior prophylaxis; if participant did not receive prior prophylaxis with rAHF-PFM, rAHF-PEG or other Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation Good: Minor increase in BBR within last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, slightly less than expected outcome according to investigator's expectation Fair: Moderate increase in BBR in last 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, somewhat less than expected outcome according to investigator's expectation Poor: Significant increase in BBR in the 12M compared with prior prophylaxis; if participant did not receive prophylaxis with rAHF-PFM, rAHF-PEG or other FVIII, little to no benefit according to investigator's expectation
Measure: Overall effectiveness assessment for prophylaxis therapy Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Evaluation of patients´ compliance to prescribed prophylactic treatment will be performed by the treating physician. Compliance will be categorized according to a 4-point table (Highly compliant, Fairly compliant, Moderately compliant, Poorly compliant)
Measure: Compliance with the dosing prescribed and its relationship with effectiveness Time: Annual/Interval visits:- Up to 8 years if rAHF-PFM alone;- Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years;- Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Excellent: Bleed episodes typically respond to same or fewer number of infusion and same or lower dose as compared with previous on-demand treatment or investigator's expectation Good: Most bleed episodes typically respond to same number of infusion and dose but some require more infusions or higher dose as compared with previous on-demand treatment or investigator's expectation Fair: Bleed episodes typically require more infusions and/or higher dose than expected as compared with previous on-demand treatment or investigator's expectation Poor: Bleed episodes routinely fail to respond to same number of infusion and dose and require additional or different factor concentrate for hemostatic control as compared with previous on-demand treatment or investigator's expectation
Measure: Overall effectiveness assessment for on-demand treatment Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Excellent: Full relief of pain and cessation of bleeding as evidenced by objective signs (e.g., swelling, tenderness, irritability, inconsolability, and decreased range of motion in the case of musculoskeletal hemorrhage) within approximately 8 hours of a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after the infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable or slight relief of pain and slight improvement in signs of bleeding within approximately 8 hours after the infusion. Requires more than 1 infusion for complete resolution. Poor: No improvement or condition worsens.
Measure: Global effectiveness assessment for on-demand treatment Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Measure: Number of rAHF-PFM or rAHF-PEG units required for bleed cessation Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitDescription: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
Measure: Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation Time: Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visitMeasure: Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; and Termination visit
Measure: Incidence of pseudo tumor development Time: Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: The the lHAL measures activities involving the upper extremities, basic activities involving ower extremities and complex activities involving the lower extremities as well as an overall physical activity score for adults.
Measure: Quality of Life: HAL questionnaire - for adult patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The SF-12v2 measures generic health-related quality of life for adults.
Measure: Quality of Life: SF-12v2 questionnaire - for adult patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The EQ-5D measures health utility in adult participants.
Measure: Quality of Life: EQ-5D questionnaire - for adult patients Time: Enrollment visit;Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The PedHAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for children. For participants 4-13 years of age: - PedHAL (parent version) For participants 14-17 years of age: - PedHAL (child version)
Measure: Quality of Life: PedHAL questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The SF-10 measures generic health-related quality of life for children and is parent-completed.
Measure: Quality of Life: SF-10 questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The EQ-5D measures health utility in subjects aged 14 and up.
Measure: Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain). During screening visit and on an annual basis, the investigators shall ask participants to rate the average level of chronic pain associated with hemophilia over the period of 4 weeks prior to visit date using the VAS.
Measure: Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain). Participants will be asked to provide ratings on level of acute pain associated with each bleeding episode using the VAS. The VAS scores will be recorded in the participant diary.
Measure: Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitMeasure: Number of days lost from school or work due to bleeding episodes Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visit
Description: Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG
Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 1 Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitDescription: Difference in number of weekly doses between previous regimen and rAHFPEG
Measure: Modalities of switching from a standard FVIII product to rAHF-PEG - 2 Time: Enrollment visit; Screening visit; Annual/Interval visits: - Up to 8 years if rAHF-PFM alone - Up to 8 years if rAHF-PEG alone with minimum follow up of 4 years - Up to approx. 12 years rAHF-PFM and switched to rAHF-PEG; Termination visitMeasure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels Lesser than (<)1%, Lesser Than or Equal to (<=) 2%, and <= 5% without history of inhibitor Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of therapy-related serious adverse events Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Measure: Incidence of therapy-related non-serious adverse events Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)
Description: Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients
Measure: Incidence of inhibitors after switching to rAHF-PEG Time: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)