ADVATE/ ADYNOVI Hemophilia A Outcome Database (AHEAD)

Hemophilia A Clinical Trial

— AHEAD  

Official title:

ADVATE/ ADYNOVI Hemophilia A Outcome Database

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02078427
• Other study ID #: 061001
• Status: Completed
• Start date: June 28, 2011
• Est. completion date: January 16, 2024

Study information

• Verified date: June 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 951
• Est. completion date: January 16, 2024
• Est. primary completion date: January 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• ADVATE
Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
• ADYNOVI
Antihemophilic Factor (Recombinant) Pegylated

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	South Metropolitan Health Service trading as Fiona Stanley Hospital	Murdoch	Western Australia
Austria	Kepler Universitätsklinikum Klinik für Kinder-und Jugendheilkunde	Linz
Austria	Landes Frauen und Kinderklinik Linz (LFKK Linz)	Linz
Austria	Medizinische Universitaet Wien	Wien
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Brazil	Fundação HEMOPA	Belém	Pará
Brazil	Hemocentro da UNICAMP	Campinas	São Paulo
Brazil	Hemepar - Pr	Curitiba	Paraná
Brazil	Hemoce - Ce	Fortaleza	Ceará
Brazil	Hemorgs - Rs	Porto Alegre	Parthenon
Brazil	Hemocentro Ribeirão Preto - SP	Ribeirão Preto	São Paulo
Brazil	Hemorio - Rj	Rio de Janeiro
Brazil	Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Hemocentro do Espírito Santo	Vitória	Espírito Santo
Canada	Stollery Children's Hospital, University of Alberta	Edmonton	Alberta
Canada	The Moncton City Hospital	Moncton	New Brunswick
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Sick Kids Hospital	Toronto	Ontario
Canada	St-Michael's Hospital	Toronto	Ontario
China	Beijing Children's Hospital Affiliated to Capital University of Medical Sciences	Beijing
China	Nanfang Hospital Affiliated to Nanfang Medical University	Guangzhou	Guangdong
China	The Blood Center of Shandong Province	Jinan	Shandong
China	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School	Nanjing
China	Shenzhen Children's Hospital	Shenzhen	Futian
China	Shenzhen Second People's Hospital	Shenzhen
China	Institute of Hematology, Blood Disease Hospital, PUMC&CAMS	Tianjin	Heping
China	Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
Colombia	IPS FUSA SAS Centro Integral de Coagulacion	Atlantico
Colombia	Integral Solutions SD SAS	Bogotá
Colombia	Fundación Oftalmológica de Santander FOSCAL	Floridablanca
Czechia	Fakultní nemocnice Brno	Brno
Czechia	Fakultní nemocnice Ostrava	Ostrava
Czechia	Fakultní nemocnice Ostrava, Oddelení detské hematologie a hematoonkologie	Ostrava
Czechia	Fakultní nemocnice v Motole	Praha 5
Denmark	Rigshospitalet	Copenhagen
France	"Hôpital Morvan CHRU de Brest"	Brest
France	CHU Côte de Nacre - CRTH	CAEN Cedex
France	Centre Hospitalier Générale - CTH	Chambery Cedex
France	CTRH - CHU Bocage	Dijon Cedex
France	Hôpital André Mignot	Le Chesnay Cedex
France	Hôpital de la Mère et de l'Enfant - CHU de LIMOGES	LIMOGES cedex
France	CHRU Hôtel Dieu - CRTH	Nantes Cedex
France	Hôpital Cochin	Paris
France	CHU de Reims Hôpital Maison Blanche - CRTH	Reims Cedex
France	Centre Régional de Traitement de l'Hémophilie et des Maladies hémorragiques. CHU de Rennes - Hôpital Pontchaillou	RENNES Cedex 09
France	CHRU Charles Nicolle	Rouen
France	CIC	Saint Priest en Jarez
France	CHRU Purpan CRTH - Pavillon Sénac	Toulouse Cedex 9
Greece	Aghia Sofia Children's Hospital	Goudi	Athens
Greece	Laikon General Hospital	Goudi	Athens
Greece	General Hospital of Thessaloniki "Ippokratio"	Thessaloniki
Hungary	Heim Pál Gyermekkórház	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Mohács City Hospital	Mohács
Hungary	Jósa András County Hospital	Nyíregyháza
Hungary	Markusovszky Hospital	Szombathely
Italy	Azienda Ospedaliera Policlinico Consorziale Di Bari	Bari
Italy	Policlinico S Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria Vittorio Emanuele, Ferrarotto, S. Bambino	Catania
Italy	Ospedale Pugliese -Ciaccio	Catanzaro
Italy	Az. Osp. Univ. Careggi	Firenze
Italy	Ospedale di Macerata	Macerata
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliera di Padova Clinica Medica II	Padova
Italy	AOUP P. Giaccone	Palermo
Italy	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Calabria
Italy	Ospedale Pediatrico Bambino Gesù	Roma
Italy	Policlinico Universitario Gemelli	Roma
Italy	Università degli studi di Roma "La Sapienza"	Roma
Italy	Centro Emofilia e Coagulopatie Rare	Scorrano
Italy	Ospedale Molinette	Torino
Norway	Rikshospitalet	Oslo
Norway	Rikshospitalet, Oslo University Hospital	Oslo
Poland	Szpital Uniwersytecki nr 1 im. dr Andrzeja Jurasza	Bydgoszcz
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1	Gdansk
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny	Warszawa
Poland	Uniwersytecki Szpital Kliniczny we Wroclawiu	Wroclaw
Portugal	Centro Hospitalar e Universitade de Coimbra	Coimbra
Portugal	Centro Hospitalar Lisboa Norte Hospital de Sta. Maria	Lisboa
Portugal	Hospital do Divino Espírito Santo	Ponta Delgada	Açores
Portugal	Centro Hospitalar de São João, E.P.E.	Porto
Russian Federation	SBHI Chelyabinsk Regional Children's Clinical Hospital	Chelyabinsk
Russian Federation	Federal State Budget Institution "Hematology Research Center" of Ministry of Healthcare of Russian Federation	Moscow
Russian Federation	SBHI of the Republic of Kareliya Republican Hospital n.a. V.A. Baranov	Petrozavodsk
Russian Federation	State Budget Healthcare Institution of Saint-Petersburg "City polyclinic #37"	Saint Petersburg
Russian Federation	Clinics of FSBEI High Education Samara SMU of MoH of Russia	Samara
Slovenia	University Medical Centre Ljubljana	Ljubljana
Spain	Hospital Teresa Herrera-Materno Infantil	A Coruña
Spain	Hospital Hospital Sant Joan de Déu	Barcelona
Spain	Hospital Universitari Vall d'Hebron (HUVH)	Barcelona
Spain	Hospital Universitario Son Espases	Palma de Mallorca
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Kliniska studier i Sverige - Forum Söder	Malmö
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Switzerland	Universitätsspital Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Luzerner Kantonsspital	Luzern 17
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	FMH Kinder und Jugendmedizin, im Wabern-Zentrum	Wabern
Switzerland	Kinderspital Zürich	Zürich
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	Hampshire Hospitals NHS Foundation Trust, Basingstoke and North Hampshire Hospital	Basingstoke	Hampshire
United Kingdom	Cambridge University Hospital NHS Foundation Trust, Addenbrooke's Hospital	Cambridge
United Kingdom	East Kent Hospitals University Foundation Trust, Kent & Canterbury Hospital	Canterbury
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Baxalta now part of Shire	Baxalta Innovations GmbH, now part of Shire

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czechia,  Denmark,  France,  Greece,  Hungary,  Italy,  Norway,  Poland,  Portugal,  Russian Federation,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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