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

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

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: ADVATE; Biological: ADYNOVI

Detailed Description

ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD)

• Study Type: Observational
• Enrollment (Actual): 951

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6050
      • South Metropolitan Health Service trading as Fiona Stanley Hospital
• Austria
  • Linz, Austria, 4017
    • Landes Frauen und Kinderklinik Linz (LFKK Linz)
  • Linz, Austria, 4020
    • Kepler Universitätsklinikum Klinik für Kinder-und Jugendheilkunde
  • Wien, Austria, 1090
    • Medizinische Universitaet Wien
• Belgium
  • Bruxelles, Belgium, B-1200
    • Cliniques Universitaires Saint-luc
• Brazil
  • Rio de Janeiro, Brazil, 20211030
    • Hemorio - Rj
  • São Paulo, Brazil, 5403000
    • Faculdade de Medicina da Universidade de Sao Paulo
  • Ceará
    • Fortaleza, Ceará, Brazil, 60431086
      • Hemoce - Ce
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29040-090
      • Hemocentro do Espírito Santo
  • Paraná
    • Curitiba, Paraná, Brazil, 80045-145
      • Hemepar - Pr
  • Parthenon
    • Porto Alegre, Parthenon, Brazil, 90650-000
      • Hemorgs - Rs
  • Pará
    • Belém, Pará, Brazil, 66033-000
      • Fundação HEMOPA
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083-970
      • Hemocentro Da UNICAMP
    • Ribeirão Preto, São Paulo, Brazil, 14051140
      • Hemocentro Ribeirão Preto - SP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital, University of Alberta
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton City Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St-Michael's Hospital
    • Toronto, Ontario, Canada, M5G 1X8
      • Sick Kids Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• China
  • Beijing, China, 100045
    • Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
  • Nanjing, China
    • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
  • Shenzhen, China, 518037
    • Shenzhen Second People's Hospital
  • Futian
    • Shenzhen, Futian, China
      • Shenzhen Children's Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital Affiliated to Nanfang Medical University
  • Heping
    • Tianjin, Heping, China
      • Institute of Hematology, Blood Disease Hospital, PUMC&CAMS
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221006
      • The Affiliated Hospital of Xuzhou Medical University
  • Shandong
    • Jinan, Shandong, China
      • The Blood Center of Shandong Province
• Colombia
  • Atlantico, Colombia
    • IPS FUSA SAS Centro Integral de Coagulacion
  • Bogotá, Colombia
    • Integral Solutions SD SAS
  • Floridablanca, Colombia, 681004
    • Fundación Oftalmológica de Santander FOSCAL
• Czechia
  • Brno, Czechia, 613 00
    • Fakultni nemocnice Brno
  • Ostrava, Czechia, 70852
    • Fakultni Nemocnice Ostrava
  • Ostrava, Czechia, 70852
    • Fakultní nemocnice Ostrava, Oddělení dětské hematologie a hematoonkologie
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• France
  • Brest, France, 29200
    • "Hôpital Morvan CHRU de Brest"
  • CAEN Cedex, France, 14033
    • CHU Côte de Nacre - CRTH
  • Chambery Cedex, France, 73011
    • Centre Hospitalier Générale - CTH
  • Dijon Cedex, France, 21079
    • CTRH - CHU Bocage
  • LIMOGES cedex, France, 87043
    • Hôpital de la mère et de l'enfant - CHU de Limoges
  • Le Chesnay Cedex, France, 78157
    • Hopital Andre Mignot
  • Nantes Cedex, France, 44093
    • CHRU Hôtel Dieu - CRTH
  • Paris, France, 75014
    • Hopital Cochin
  • RENNES Cedex 09, France, 35033
    • Centre Régional de Traitement de l'Hémophilie et des Maladies hémorragiques. CHU de Rennes - Hôpital Pontchaillou
  • Reims Cedex, France, 51092
    • CHU de Reims Hôpital Maison Blanche - CRTH
  • Rouen, France, 76031
    • CHRU Charles Nicolle
  • Saint Priest en Jarez, France, 42270
    • CIC
  • Toulouse Cedex 9, France, 31059
    • CHRU Purpan CRTH - Pavillon Sénac
• Greece
  • Thessaloniki, Greece, 546 42
    • General Hospital of Thessaloniki "Ippokratio"
  • Athens
    • Goudi, Athens, Greece, 11527
      • Aghia Sofia Children's Hospital
    • Goudi, Athens, Greece, 11527
      • Laikon General Hospital
• Hungary
  • Budapest, Hungary, H-1089
    • Heim Pál Gyermekkórház
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Klinikai Kozpont
  • Mohács, Hungary, H-7700
    • Mohács City Hospital
  • Nyíregyháza, Hungary, H-4400
    • Jósa András County Hospital
  • Szombathely, Hungary, H-9700
    • Markusovszky Hospital
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliera Policlinico Consorziale Di Bari
  • Bologna, Italy, 40138
    • Policlinico S Orsola Malpighi
  • Catania, Italy, 95120
    • Azienda Ospedaliera Universitaria Vittorio Emanuele, Ferrarotto, S. Bambino
  • Catanzaro, Italy, 88100
    • Ospedale Pugliese -Ciaccio
  • Firenze, Italy, 50134
    • Az. Osp. Univ. Careggi
  • Macerata, Italy, 62100
    • Ospedale Di Macerata
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Padova, Italy, 35100
    • Azienda Ospedaliera di Padova Clinica Medica II
  • Palermo, Italy, 90133
    • AOUP P. Giaccone
  • Reggio Calabria, Italy, 89123
    • Azienda Ospedaliera Bianchi Melacrino Morelli
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesu
  • Roma, Italy, 00168
    • Policlinico Universitario Gemelli
  • Roma, Italy, 00161
    • Università degli studi di Roma "La Sapienza"
  • Scorrano, Italy, 73025
    • Centro Emofilia e Coagulopatie Rare
  • Torino, Italy, 10126
    • Ospedale Molinette
• Norway
  • Oslo, Norway, N-0027
    • Rikshospitalet
  • Oslo, Norway, N-0424
    • Rikshospitalet, Oslo University Hospital
• Poland
  • Bydgoszcz, Poland, 85-094
    • Szpital Uniwersytecki nr 1 im. dr Andrzeja Jurasza
  • Gdansk, Poland, 80-952
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Warszawa, Poland, 02-091
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny
  • Wroclaw, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny we Wrocławiu
• Portugal
  • Coimbra, Portugal, 3000-602
    • Centro Hospitalar e Universitade de Coimbra
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte Hospital de Sta. Maria
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, E.P.E.
  • Açores
    • Ponta Delgada, Açores, Portugal, 9500-370
      • Hospital Do Divino Espirito Santo
• Russian Federation
  • Chelyabinsk, Russian Federation
    • SBHI Chelyabinsk Regional Children's Clinical Hospital
  • Moscow, Russian Federation, 125167
    • Federal State Budget Institution "Hematology Research Center" of Ministry of Healthcare of Russian Federation
  • Petrozavodsk, Russian Federation
    • SBHI of the Republic of Kareliya Republican Hospital n.a. V.A. Baranov
  • Saint Petersburg, Russian Federation, 191186
    • State Budget Healthcare Institution of Saint-Petersburg "City polyclinic #37"
  • Samara, Russian Federation, 443079
    • Clinics of FSBEI High Education Samara SMU of MoH of Russia
• Slovenia
  • Ljubljana, Slovenia, SI-1000
    • University Medical Centre Ljubljana
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera-Materno Infantil
  • Barcelona, Spain, 08035
    • Hospital Hospital Sant Joan de Déu
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron (HUVH)
  • Palma de Mallorca, Spain, 07120
    • Hospital Universitario Son Espases
• Sweden
  • Gothenburg, Sweden, SE 41345
    • Sahlgrenska University Hospital
  • Malmö, Sweden, SE-205 02
    • Kliniska studier i Sverige - Forum Söder
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna
• Switzerland
  • Basel, Switzerland, CH-4031
    • Universitätsspital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Luzern 17, Switzerland, CH-6000
    • Luzerner Kantonsspital
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Wabern, Switzerland, CH-3084
    • FMH Kinder und Jugendmedizin, im Wabern-Zentrum
  • Zürich, Switzerland, CH-8032
    • Kinderspital Zurich
  • Zürich, Switzerland, CH-8091
    • UniversitätsSpital Zürich
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospital NHS Foundation Trust, Addenbrooke's Hospital
  • Canterbury, United Kingdom, CT1 3NG
    • East Kent Hospitals University Foundation Trust, Kent & Canterbury Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond street Hospital for Children NHS Trust
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
rAHF-PFM; Participants treated with rAHF-PFM alone	Biological: ADVATE; Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method; Other Names: octocog alfa; rAHF-PFM
rAHF-PEG; Participants treated with rAHF-PEG alone	Biological: ADYNOVI; Antihemophilic Factor (Recombinant) Pegylated; Other Names: rurioctocog alfa pegol; rAHF-PEG
rAHF-PFM then rAHF-PEG; Participants treated with rAHF-PFM and subsequently switched to rAHF-PEG	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Joint Health Outcomes - Assessed by Physical Exam Using Only the Pain, Bleeding, and Physical Exam Parameters of the Gilbert Scale	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.	Up to approximately 12 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleed Rate, All Joints	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.	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
Annualized Bleed Rate, All Bleeds	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.	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
Annualized bleed rate, pre-existing target joints at baseline	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.	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 New Target Joints	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.	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
Status of joint health by X-ray by Pettersson scale	The status of joint health by X-ray by Pettersson score will be summarized for each observational year.	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.
Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS)	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	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
Status of joint health using the Hemophilia Joint Health Score (HJHS)	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.	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
Overall effectiveness assessment for prophylaxis therapy	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	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
Compliance with the dosing prescribed and its relationship with effectiveness	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)	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
Overall effectiveness assessment for on-demand treatment	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	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
Global effectiveness assessment for on-demand treatment	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.	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
Number of rAHF-PFM or rAHF-PEG units required for bleed cessation	Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)	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
Number of rAHF-PFM or rAHF-PEG infusions required for bleed cessation	Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (rAHF-PFM) Antihemophilic Factor (Recombinant) - Pegylated (rAHF-PEG)	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 target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy		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		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	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.	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
Quality of Life: SF-12v2 questionnaire - for adult patients	The SF-12v2 measures generic health-related quality of life for adults.	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
Quality of Life: EQ-5D questionnaire - for adult patients	The EQ-5D measures health utility in adult participants.	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
Quality of Life: PedHAL questionnaire - for pediatric patients	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)	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
Quality of Life: SF-10 questionnaire - for pediatric patients	The SF-10 measures generic health-related quality of life for children and is parent-completed.	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
Quality of Life: EQ-5D (14 and up) questionnaire - for pediatric patients	The EQ-5D measures health utility in subjects aged 14 and up.	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
Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS)	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.	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
Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS)	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.	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
Number of days lost from school or work due to bleeding episodes		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	Difference in number of weekly prophylactic infusions between previous regimen and rAHF-PEG	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 - 2	Difference in number of weekly doses between previous regimen and rAHFPEG	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
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		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		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%		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		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		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	Incidence of inhibitors after switching to rAHF-PEG in the same subgroups of patients	Throughout the study period of up to approximately: 8 years (rAHF-PFM alone), or 12 years (rAHF-PEG alone or after receiving rAHF-PFM)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Baxalta Innovations GmbH, now part of Shire
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2011
• Primary Completion (Actual): January 16, 2024
• Study Completion (Actual): January 16, 2024

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimated): March 5, 2014

Study Record Updates

• Last Update Posted (Actual): June 17, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; BAX 855
• Other Study ID Numbers: 061001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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