BAX 855 Continuation

A Phase 3b Continuation Study of the Safety and Efficacy of PEGylated Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in Previously Treated Patients With Severe Hemophilia A

To continue the evaluation of the safety and efficacy of BAX 855 for prophylaxis and treatment of bleeding episodes in adult and pediatric previously treated patients (PTPs) aged ≤ 75 years of age with severe hemophilia A.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: BAX855

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Hospital
• Austria
  • Linz, Austria, 4020
    • Landes-Frauen-und Kinderklinik Linz
  • Vienna, Austria, 1090
    • Universitätsklinik für Innere Medizin I
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT "Sv. Georgi", EAD
  • Sofia, Bulgaria, 1527
    • SHAT of Oncohaematology Diseases
  • Varna, Bulgaria, 9010
    • MHAT 'Sv. Marina', EAD
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Olomouc, Czechia, 775 20
    • Fakultní nemocnice Olomouc
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
• Germany
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshain - Landsberger Allee
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Werlhof-Institut GmbH
  • Nordrhein Westfalen
    • Duisburg, Nordrhein Westfalen, Germany, 47051
      • Gerinnungszentrum rhein-ruhr
• Hong Kong
  • Shatin, Hong Kong, 00000
    • Prince of Wales Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Ramat-Gan, Israel, 52621
    • Chaim Sheba Medical Center
• Japan
  • Aichi-Ken
    • Nagoya-shi, Aichi-Ken, Japan, 466-8560
      • Nagoya University Hospital
  • Fukuoka-Ken
    • Kitakyushu-shi, Fukuoka-Ken, Japan, 807-8556
      • University of Occupational and Environmental Health Hospital
  • Hiroshima-Ken
    • Hiroshima-shi, Hiroshima-Ken, Japan, 734-8551
      • Hiroshima University Hospital
  • Kanagawa-Ken
    • Kawasaki-shi, Kanagawa-Ken, Japan, 216-8511
      • St. Marianna University School of Medicine Hospital
  • Nara-Ken
    • Kashihara-shi, Nara-Ken, Japan, 634-8522
      • Nara Medical University Hospital
  • Tokyo
    • Suginami City, Tokyo, Japan, 167-8515
      • Ogikubo Hospital
  • Tokyo-To
    • Shinjuku-ku, Tokyo-To, Japan, 160-0023
      • Tokyo Medical University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Daejeon, Korea, Republic of, 302-799
    • Eulji University Hospital
  • Seoul, Korea, Republic of, 134-727
    • Kyung Hee University Hospital at Gangdong
  • Ulsan, Korea, Republic of, 682-714
    • Ulsan University Hospital
  • Jeollanam-do
    • Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-763
      • Chonnam National University Hwasun Hospital
• Lithuania
  • Vilnius, Lithuania, 8661
    • Vilnius University Hospital Santariskiu Clinics, Public Institution
  • Vilnius, Lithuania, LT-08406
    • Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Pusat Darah Negara
  • Pulau Pinang, Malaysia, 10450
    • Hospital Pulau Pinang
  • Penang
    • George Town, Penang, Malaysia, 10990
      • Penang General Hospital
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Hospital Umum Sarawak
    • Sibu, Sarawak, Malaysia, 96000
      • Hospital Sibu
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Lodz, Poland, 93-510
    • Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
• Romania
  • Bucuresti, Romania, 11038
    • Sanador SRL
• Russian Federation
  • Kirov, Russian Federation, 610000
    • LLC "Alba Dent"
  • Krasnoyarsk, Russian Federation, 660022
    • Regional Clinical Hospital
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 7010
      • Hospital Universitari Son Espases
  • La Coruña
    • A Coruña, La Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruna
  • Málaga
    • Malaga, Málaga, Spain, 29010
      • Hospital Regional Universitario de Málaga
• Sweden
  • Malmo, Sweden, 21428
    • Sjukhusapoteket Malmo
  • Stockholm, Sweden, 17164
    • Karolinska
• Switzerland
  • Zuerich, Switzerland, 8091
    • UniversitaetsSpital Zuerich
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
• Turkey
  • Ankara, Turkey, 063100
    • Ankara University Medical Faculty
  • Antalya, Turkey, 07059
    • Akdeniz University Faculty of Medicine
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
• Ukraine
  • Donetsk, Ukraine, 83045
    • SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU
  • Lviv, Ukraine, 79044
    • SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
• United Kingdom
  • Oxford, United Kingdom, OX3 7LE
    • The Churchill Hospital
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8BJ
      • Bristol Royal Hospital for Children
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
    • London, Greater London, United Kingdom, SE1 7EH
      • St Thomas' Hospital
    • London, Greater London, United Kingdom, WC1E 6AG
      • Royal Free Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Royal Manchester Children's Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Childrens Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Gainesville, Florida, United States, 32610-0278
      • University of Florida College of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Peoria, Illinois, United States, 61614
      • Bleeding and Clotting Disorders Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • University of Kentucky Medical Center
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • CHILDREN'S MERCY HOSPITALS & CLINICS
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore-Long Island Jewish Health System
    • New York, New York, United States, 10065
      • New York - Presbyterian/Weill Cornell Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7016
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27705
      • DUKE University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203-6863
      • Palmetto Health Richland
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98104
      • Puget Sound Blood Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These participants will complete any additional screening assessments within 2 weeks of the previous study's end of study visit and will return to the study site within 6 (± 1) weeks of the previous study end of study visit to confirm eligibility for this continuation study.

• Participants transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study:

  1. Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study.
  2. Participant is ≤75 years of age at screening of the previous BAX 855 study.
  3. Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
  4. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
  5. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
  6. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
  7. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
• BAX 855 Naïve Participants:

BAX 855 naïve participants who are ≥ 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve participants who are < 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric previously treated patient (PTP) study is closed.

- Enrolment of BAX 855 naïve participants will only start once the sponsor has notified the study sites accordingly.

BAX 855 naïve participants who meet ALL of the following criteria are eligible for this study:

1. Participant is ≤75 years of age at screening.
2. Participant is naïve to BAX 855.
3. Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period.
4. Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs).
5. Participant aged < 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs.
6. Participant is currently receiving prophylaxis or on-demand therapy with FVIII.
7. Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
8. Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
9. Participant is HCV- by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
10. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
11. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERA

- Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies who meet ANY of the following criteria are not eligible for this study:

1. Participant had detectable factor VIII (FVIII) inhibitory antibodies (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Participant has developed FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at central laboratory in a previous BAX 855 study).
3. Participant has acquired a hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease) in a previous BAX 855 study.
4. Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening).
5. Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
6. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
7. Participant is scheduled to use other PEGylated drugs during study participation.
8. Participant is planning to take part in any other clinical study during the course of the continuation study, with the exception of any other parallel BAX 855 study.
9. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.

10. Participant is a family member or employee of the investigator.

    • BAX 855 Naïve Participants:

BAX 855 naïve participants who meet ANY of the following criteria are not eligible for this study:

1. Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Participant has history of FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening.
3. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
4. Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
5. Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening).
6. Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
7. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
8. Participant has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation.
9. Participant has participated in another clinical study involving an IP other than BAX 855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study.
10. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
11. Participant is a family member or employee of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed BAX855 prophylaxis; 45-80 IU/kg twice weekly to once per week.	Biological: BAX855; Antihemophilic Factor (Recombinant), PEGylated; Other Names: BAX 855; ADYNOVATE; PEGylated Recombinant Factor VIII
Experimental: Pharmacokinetic (PK)-tailored BAX 855 prophylaxis; PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level	Biological: BAX855; Antihemophilic Factor (Recombinant), PEGylated; Other Names: BAX 855; ADYNOVATE; PEGylated Recombinant Factor VIII

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)	Inhibitory antibodies to Factor VIII were measured by the Nijmegen modification of the Bethesda assay. Inhibitors had to be confirmed by 2 separate assessments within a 2 to 4 week period from the central laboratory.	Baseline through end of study (53 months)
Annualized Bleed Rate (ABR) - Spontaneous Bleeds	The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The ABR of spontaneous bleeds was reported separately for twice weekly, PK-t R, each of the every 5 days and every 7 days treatment regimens at the time of bleed.	Baseline through end of study (53 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Annualized Bleed Rate (ABR)	The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) was reported.	Baseline through end of study (53 months)
Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes	The participant or caregiver rated the overall treatment response at 24 (+/- 2) hours after the initiation of treatment using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.	Baseline through end of study (53 months)
BAX 855 Infusions Needed to Treat Bleeding Episodes	The BAX 855 infusions to treat each bleeding episode was determined by the participant, the participant's caregiver, and/or investigator, and was based upon the participant's response to treatment. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.	Baseline through end of study (53 months)
Total Time Intervals Between Bleeding Episodes	The time interval between bleeding episodes was calculated based upon the date and time reported for each bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.	Baseline through end of study (53 months)
Average Dose of BAX 855 Per Prophylactic Infusion	The average dose of BAX 855 per prophylactic infusion was reported.	Baseline through end of study (53 months)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an investigational product (IP), whether or not considered causally related to the IP. A serious adverse event (SAE) was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death; was life-threatening; required inpatient hospitalization or resulted in prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was a medically important event.	Baseline through end of study (53 months)
Change From Baseline in Body Temperature	Change in body temperature at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.	Baseline, end of study (53 months)
Change From Baseline in Pulse Rate	Change in pulse rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.	Baseline, end of study (53 months)
Change From Baseline in Respiratory Rate	Change in respiratory rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.	Baseline, end of study (53 months)
Change From Baseline in Blood Pressure	Change in systolic and diastolic blood pressure at pre-infusion and post-infusion at end of the study were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, SBP refers to systolic blood pressure, DBP refers to diastolic blood pressure.	Baseline, end of study (53 months)
Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.	The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen at the time of sampling, AlA refers to alanine aminotransferase, AP refers to alkaline phosphatase, AsA refers to aspartate aminotransferase.	Baseline through end of study (53 months)
Number of Participants With Shifts in Hematology Laboratory Assessments	The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, Leu refers to leukocytes, MCV refers to mean corpuscular volume, Lym/Leu refers to lymphocytes/leukocytes.	Baseline through end of study (53 months)
Number of Participants With Shifts in Lipid Panel Assessments	The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported.. In the below table, HDL refers to high density lipoprotein, LDL refers to low density lipoprotein, VLDL refers to very low density lipoprotein.	Baseline through end of study (53 months)
Number of Participants With Binding Antibodies	Binding antibodies (IgG and IgM) against FVIII, polyethylene glycol (PEG) and PEGylated FVIII (PEG-FVIII) were analyzed using enzyme-linked immunosorbent assay (ELISA).	Baseline through end of study (53 months)
Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies	Testing for binding of anti-CHO protein antibodies was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal antihuman IgG antibodies.	Baseline through end of study (53 months)
Change From Baseline in Bleed Severity	Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the bleed severity for participants >=18 years of age as: severity of spontaneous bleeding in my joints (unrelated to injury or activity), spontaneous bleeding in my muscles (unrelated to injury or activity), prolonged bleeding after injury in spite of treatment, intense pain because of bleeding event, joint pain due to active bleed and bleeding during personal hygiene routine, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.	Baseline, end of study (53 months)
Change From Baseline in Pain Severity	Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the pain severity for participants >=18 years of age as: pain because of swelling in my joints, climbing stairs, upon waking in the morning, active arthritis; constant pain, in my muscles, that needs medication; joint sensitivity to weather conditions; reduced range of joint movement, joint deformity, sleep disturbance because of pain or bleeds, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.	Baseline, end of study (53 months)
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)	HRQoL in participants aged >=14 years was measured using the SF-36 questionnaire. The questionnaire was divided into 8 domains and scored as: physical functioning (1=yes, limited a lot to 3=no, not limited at all), role-physical (1=all of the time to 5=none of the time), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), vitality (1=none of the time to 5=all of the time), social functioning (1=all of the time: to 5=none of the time), role emotional (1=all of the time to 5=none of the time) and mental health (1=all of the time to 5=none of the time). The score for each domain is then to be transformed to a 0-100 range as [(actual raw score-lowest possible raw score)/possible raw score range]*100. Positive change scores indicate improved HRQoL. in the below table 'FDR' indicates fixed dose regimen, 'PK-tr' indicates pharmacokinetically tailored regimen and 'n' refers to the number of participants evaluable for this endpoint.	Baseline, end of study (53 months)
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire	HRQoL in participants aged <14 years was measured using the PedsQL. It capture data for the following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial functioning, physical health and a total score. Each question of the PedsQL was scored as Never: 100, almost never: 75, sometimes: 50, often: 25, almost always: 0. The mean of the individual question scores was calculated. Lower scores on the PedsQL indicating worse HRQoL. Here, FDR refers to fixed dose regimen, PK-t R refers to PK-tailored regimen. Here 'n' refers to the number of participants evaluable for this endpoint. Here 'n' refers to the number of participants evaluable for this endpoint.	Baseline, end of study (53 months)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Baxalta Innovations GmbH, now part of Shire

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2013
• Primary Completion (Actual): March 2, 2018
• Study Completion (Actual): March 2, 2018

Study Registration Dates

• First Submitted: September 16, 2013
• First Submitted That Met QC Criteria: September 16, 2013
• First Posted (Estimate): September 18, 2013

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

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; Factor VIII; BAX 855
• Other Study ID Numbers: 261302; 2013-002236-24 (EudraCT Number)

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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