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ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD) (AHEAD)

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ClinicalTrials.gov Identifier: NCT02078427
Recruitment Status : Recruiting
First Posted : March 5, 2014
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Tracking Information
First Submitted Date March 3, 2014
First Posted Date March 5, 2014
Last Update Posted Date July 8, 2019
Actual Study Start Date June 29, 2011
Estimated Primary Completion Date January 15, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 7, 2019)
Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale [ Time Frame: Up to approximately 12 years ]
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.
Original Primary Outcome Measures
 (submitted: March 4, 2014)
Joint health outcomes - assessed by physical exam using only the pain, bleeding, and physical exam parameters of the Gilbert Scale. [ Time Frame: 4 years ]
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.
Change History Complete list of historical versions of study NCT02078427 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: May 7, 2019)
  • Annualized Bleed Rate, All Joints [ Time Frame: 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 ]
    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.
  • Annualized Bleed Rate, All Bleeds [ Time Frame: 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 ]
    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.
  • Annualized bleed rate, pre-existing target joints at baseline [ Time Frame: 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 ]
    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.
  • Incidence of New Target Joints [ Time Frame: 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 ]
    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.
  • Status of joint health by X-ray by Pettersson scale [ Time Frame: 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. ]
    The status of joint health by X-ray by Pettersson score will be summarized for each observational year.
  • Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) [ Time Frame: 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 ]
    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
  • Status of joint health using the Hemophilia Joint Health Score (HJHS) [ Time Frame: 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 ]
    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.
  • Overall effectiveness assessment for prophylaxis therapy [ Time Frame: 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 ]
    • 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
  • Compliance with the dosing prescribed and its relationship with effectiveness [ Time Frame: 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 ]
    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)
  • Overall effectiveness assessment for on-demand treatment [ Time Frame: 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 ]
    • 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
  • Global effectiveness assessment for on-demand treatment [ Time Frame: 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 ]
    • 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.
  • Number of rAHF-PFM or rAHF-PEG units required for bleed cessation [ Time Frame: 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 ]
    Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
  • Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation [ Time Frame: 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 ]
    Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)
  • Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy [ Time Frame: 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 ]
  • Incidence of pseudo tumor development [ Time Frame: 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 ]
  • Quality of Life: HAL questionnaire - for adult patients [ Time Frame: 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 ]
    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.
  • Quality of Life: SF-12v2 questionnaire - for adult patients [ Time Frame: 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 ]
    The SF-12v2 measures generic health-related quality of life for adults.
  • Quality of Life: EQ-5D questionnaire - for adult patients [ Time Frame: 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 ]
    The EQ-5D measures health utility in adult participants.
  • Quality of Life: PedHAL questionnaire - for pediatric patients [ Time Frame: 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 ]
    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)
  • Quality of Life: SF-10 questionnaire - for pediatric patients [ Time Frame: 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 ]
    The SF-10 measures generic health-related quality of life for children and is parent-completed.
  • Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients [ Time Frame: 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 ]
    The EQ-5D measures health utility in subjects aged 14 and up.
  • Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) [ Time Frame: 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 ]
    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.
  • Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) [ Time Frame: 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 ]
    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.
  • Number of days lost from school or work due to bleeding episodes [ Time Frame: 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 ]
  • Modalities of switching from a standard FVIII product to rAHF-PEG - 1 [ Time Frame: 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 ]
    Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG
  • Modalities of switching from a standard FVIII product to rAHF-PEG - 2 [ Time Frame: 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 ]
    Difference in number of weekly doses between previous regimen and rAHFPEG
  • 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 Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
  • Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% with history of inhibitor [ Time Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
  • Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, <=2%, and <= 5% [ Time Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
  • Incidence of therapy-related serious adverse events [ Time Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
  • Incidence of therapy-related non-serious adverse events [ Time Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
  • Incidence of inhibitors after switching to rAHF-PEG [ Time Frame: Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM) ]
    Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients
Original Secondary Outcome Measures
 (submitted: March 4, 2014)
  • Annualized Bleed Rate, All Joints [ Time Frame: 4 years ]
    The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants.
  • Annualized Bleed Rate, All Bleeds [ Time Frame: 4 years ]
    The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.
  • Annualized bleed rate, pre-existing target joints at baseline [ Time Frame: 4 years ]
    The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants.
  • Incidence of New Target Joints [ Time Frame: 4 years ]
    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. The time to the first occurrence of a new target joint in a participant will be analyzed by the Kaplan-Meier technique.
  • Status of joint health by X-ray by Pettersson scale [ Time Frame: 4 years ]
    The status of joint health by X-ray by Pettersson score will be summarized for timepoints 0, 1, 2, 3, and 4 years after study start. Linear interpolation (for any time interval) and linear extrapolation (for up to 0.5 years) will be used to derive an estimate of the score at these timepoints.
  • Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) [ Time Frame: 0, 1, 2, 3, and 4 years ]
    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
  • Status of joint health using the Hemophilia Joint Health Score (HJHS) [ Time Frame: 0, 1, 2, 3, and 4 years ]
    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.
  • Overall effectiveness assessment for prophylaxis therapy [ Time Frame: 4 years, Throughout the study ]
    • Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with previous prophylaxis; if participant did not receive previous prophylaxis with rAHF-PFM or another Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation
    • Good: Minor increase in BBR within last 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, slightly less than expected outcome according to investigator's expectation
    • Fair: Moderate increase in BBR in last 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, somewhat less than expected outcome according to investigator's expectation
    • Poor: Significant increase in BBR in the 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, little to no benefit according to investigator's expectation
  • Overall effectiveness assessment for on-demand treatment [ Time Frame: 4 years, Throughout the study ]
    • 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
  • Global effectiveness assessment for on-demand treatment [ Time Frame: 4 years, Throughout the study ]
    • 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.
  • Number of ADVATE units required for bleed cessation [ Time Frame: 4 years, Throughout the study ]
  • Number of ADVATE infusions required for bleed cessation [ Time Frame: 4 years, Throughout the study ]
  • Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy [ Time Frame: 4 years, Throughout the study ]
  • Incidence of pseudo tumor development [ Time Frame: 4 years, Throughout the study ]
  • Quality of Life: HAL questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The HAL 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 adults.
  • Quality of Life: SF-12v2 questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The SF-12v2 measures generic health-related quality of life for adults.
  • Quality of Life: EQ-5D questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The EQ-5D measures health utility in subjects aged 13 and up.
  • Quality of Life: PedHAL questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    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)
  • Quality of Life: SF-10 questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The SF-10 measures generic health-related quality of life for children and is parent-completed.
  • Quality of Life: EQ-5D (13 and up) questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The EQ-5D measures health utility in subjects aged 13 and up.
  • Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) [ Time Frame: Year 0, 1, 2, 3 and 4 ]
    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.
  • Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) [ Time Frame: Year 1, 2, 3 and 4 ]
    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.
  • Number of days lost from school or work due to bleeding episodes [ Time Frame: Year 1, 2, 3 and 4 ]
  • Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% without history of inhibitor [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  • Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% with history of inhibitor [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  • Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  • Incidence of therapy-related serious adverse events [ Time Frame: 4 years, Throughout the study ]
  • Incidence of therapy-related non-serious adverse events [ Time Frame: 4 years, Throughout the study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD)
Official Title ADVATE/ ADYNOVI Hemophilia A Outcome Database
Brief Summary 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
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population The study population will include male and female participants of any race and age who have a diagnosis of hemophilia A (Factor VIII (FVIII) =5%). Participants must have been prescribed rAHF-PFM or rAHF-PEG for the management of hemophilia A by the treating physician prior to the decision to enroll in the study.
Condition Hemophilia A
Intervention
  • Biological: ADVATE
    Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
    Other Names:
    • octocog alfa
    • rAHF-PFM
  • Biological: ADYNOVI
    Antihemophilic Factor (Recombinant) Pegylated
    Other Names:
    • rurioctocog alfa pegol
    • rAHF-PEG
Study Groups/Cohorts
  • rAHF-PFM
    Participants treated with rAHF-PFM alone
    Intervention: Biological: ADVATE
  • rAHF-PEG
    Participants treated with rAHF-PEG alone
    Intervention: Biological: ADYNOVI
  • rAHF-PFM then rAHF-PEG
    Participants treated with rAHF-PFM and subsequently switched to rAHF-PEG
    Interventions:
    • Biological: ADVATE
    • Biological: ADYNOVI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 7, 2019)
630
Original Estimated Enrollment
 (submitted: March 4, 2014)
350
Estimated Study Completion Date January 15, 2025
Estimated Primary Completion Date January 15, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Participant has hemophilia A {FVIII lesser than or equal to (<=)5%}
  • Participant is prescribed Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) or Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG) by the treating physician
  • Participant or participant's legally authorized representative provides informed consent

Exclusion Criteria:

  • Participant has known hypersensitivity to the active substance or any of the excipients
  • Participant has known allergic reaction to mouse or hamster proteins
  • Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving another FVIII concentrate or device during the course of this study
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com
Listed Location Countries France,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Colombia,   Czechia,   Denmark,   Greece,   Hungary,   Italy,   Norway,   Poland,   Portugal,   Russian Federation,   Slovenia,   Spain,   Sweden,   Switzerland,   United Kingdom
Removed Location Countries Czech Republic,   United States
 
Administrative Information
NCT Number NCT02078427
Other Study ID Numbers 061001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers
Responsible Party Shire ( Baxalta now part of Shire )
Study Sponsor Baxalta now part of Shire
Collaborators Baxalta Innovations GmbH, now part of Shire
Investigators
Study Director: Study Director Shire
PRS Account Shire
Verification Date July 2019