Hemophilia APhase 3NCT01945593
BAX 855 Continuation
A Phase 3 study testing BAX855 in people with Hemophilia A, run by Baxalta now part of Shire at 89 sites in 23 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Hemophilia A
- What is being tested?
- BAX855
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 218 participants
- Where
- 89 sitesin 23 countries
- Study dates
- 15 Oct 2013to 2 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study.
- Participant is ≤75 years of age at screening of the previous BAX 855 study.
- Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
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- 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.
- 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.
- 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.
- 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:
- Participant is ≤75 years of age at screening.
- Participant is naïve to BAX 855.
- Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period.
- Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs).
- Participant aged < 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs.
- Participant is currently receiving prophylaxis or on-demand therapy with FVIII.
- Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
- Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
- 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.
- 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.
- Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
Who cannot join
- 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:
- 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.
- 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).
- 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.
- Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening).
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- Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
- Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
- Participant is scheduled to use other PEGylated drugs during study participation.
- 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.
- 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.
- 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:
- Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
- 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.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
- Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
- Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening).
- Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
- Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
- 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.
- 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.
- 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.
- Participant is a family member or employee of the investigator.
Trial locations and contacts
89 sites in 23 countries.
89 sites in 23 countries
United States21 sites
University of Colorado
Aurora, Colorado, 80045
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7016
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2605
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Palmetto Health Richland
Columbia, South Carolina, 29203-6863
Nationwide Children's Hospital
Columbus, Ohio, 43205
Duke University Medical Center
Durham, North Carolina, 27705
University of Florida College of Medicine
Gainesville, Florida, 32610-0278
Penn State Hershey Cancer Center
Hershey, Pennsylvania, 17033
Children's Mercy Hospitals & Clinics
Kansas City, Missouri, 64108
University of Kentucky Medical Center
Lexington, Kentucky, 40536-0284
University of Louisville
Louisville, Kentucky, 40202
North Shore-Long Island Jewish Health System
New Hyde Park, New York, 11040
Tulane University School of Medicine
New Orleans, Louisiana, 70112
New York - Presbyterian/Weill Cornell Medical Center
New York, New York, 10065
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Bleeding and Clotting Disorders Institute
Peoria, Illinois, 61614
Phoenix Childrens Hospital
Phoenix, Arizona, 85016-7710
University of Utah
Salt Lake City, Utah, 84108
Puget Sound Blood Group
Seattle, Washington, 98104
United Kingdom9 sites
Birmingham Children's Hospital
Birmingham, West Midlands, B4 6NH
Bristol Royal Hospital for Children
Bristol, Avon, BS2 8BJ
Leicester Royal Infirmary
Leicester, Leicestershire, LE1 5WW
St Thomas' Hospital
London, Greater London, SE1 7EH
Royal Free Hospital
London, Greater London, WC1E 6AG
Great Ormond Street Hospital for Children
London, Greater London, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, Greater Manchester, M13 9WL
The Churchill Hospital
Oxford, OX3 7LE
Southampton General Hospital
Southampton, Hampshire, SO16 6YD
Japan7 sites
Hiroshima University Hospital
Hiroshima, Hiroshima, 734-8551
Nara Medical University Hospital
Kashihara-shi, Nara, 634-8522
St. Marianna University School of Medicine Hospital
Kawasaki-shi, Kanagawa, 216-8511
University of Occupational and Environmental Health Hospital
Kitakyushu-shi, Fukuoka, 807-8556
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
Tokyo Medical University Hospital
Shinjuku-ku, Tokyo-To, 160-0023
Ogikubo Hospital
Suginami City, Tokyo, 167-8515
Malaysia6 sites
Hospital Ampang
Ampang, Selangor, 68000
Penang General Hospital
George Town, Pulau Pinang, 10990
Pusat Darah Negara
Kuala Lumpur, 50400
Hospital Umum Sarawak
Kuching, Sarawak, 93586
Hospital Pulau Pinang
Pulau Pinang, 10450
Hospital Sibu
Sibu, Sarawak, 96000
South Korea5 sites
Pusan National University Hospital
Busan, 602-739
Eulji University Hospital
Daejeon, 302-799
Chonnam National University Hwasun Hospital
Hwasun-gun, Jeollanam-do, 519-763
Kyung Hee University Hospital at Gangdong
Seoul, 134-727
Ulsan University Hospital
Ulsan, 682-714
Spain5 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, La Coruña, 15006
Hospital Universitario La Paz
Madrid, 28046
Hospital Regional Universitario de Malaga
Málaga, Málaga, 29010
Hospital Universitari Son Espases
Palma de Mallorca, Balearic Islands, 7010
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Germany4 sites
Vivantes Klinikum im Friedrichshain - Landsberger Allee
Berlin, 10249
Gerinnungszentrum Rhein-Ruhr
Duisburg, North Rhine-Westphalia, 47051
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
Werlhof-Institut GmbH
Hanover, Lower Saxony, 30159
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Fremantle Hospital
Fremantle, Western Australia, 6160
The Alfred Hospital
Melbourne, Victoria, 3004
Bulgaria3 sites
UMHAT "Sv. Georgi", EAD
Plovdiv, 4002
SHAT of Oncohaematology Diseases
Sofia, 1527
MHAT 'Sv. Marina', EAD
Varna, 9010
Czechia3 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni nemocnice Olomouc
Olomouc, 775 20
Fakultni nemocnice v Motole
Prague, 150 06
Turkey (Türkiye)3 sites
Ankara University Medical Faculty
Ankara, 063100
Akdeniz University Faculty of Medicine
Antalya, 07059
Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34098
Austria2 sites
Landes-Frauen-und Kinderklinik Linz
Linz, 4020
Universitatsklinik fur Innere Medizin I
Vienna, 1090
Israel2 sites
Rambam Health Care Campus
Haifa, 3109601
Chaim Sheba Medical Center
Ramat Gan, 52621
Lithuania2 sites
Vilnius University Hospital Santariskiu Clinics, Public Institution
Vilnius, 8661
Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
Vilnius, LT-08406
Poland2 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
Lodz, 93-510
Russia2 sites
LLC "Alba Dent"
Kirov, 610000
Regional Clinical Hospital
Krasnoyarsk, 660022
Taiwan2 sites
Taichung Veterans General Hospital
Taichung, 40705
Tri-Service General Hospital
Taipei, 11490
Ukraine2 sites
SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU
Donetsk, 83045
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
Lviv, 79044
About this study
Official title: 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.
- Conditions
- Hemophilia A
- Being tested
- BAX855
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAX855Biological
Also called ADYNOVATE, BAX 855, PEGylated Recombinant Factor VIII
Antihemophilic Factor (Recombinant), PEGylated
| Study group | Role | What they receive |
|---|---|---|
| Fixed BAX855 prophylaxis | Experimental | 45-80 IU/kg twice weekly to once per week. Receives: Biological: BAX855 |
| Pharmacokinetic (PK)-tailored BAX 855 prophylaxis | Experimental | PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level Receives: Biological: BAX855 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline through end of study (53 months)
Secondary outcomes (19)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, end of study (53 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2013 (estimated)
- Study start15 Oct 2013
- Primary completion2 Mar 2018
- Study completion2 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 218 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01945593
- Sponsor's protocol ID
- 261302
- Other IDs
- 2013-002236-24
- Status last verified
- Apr 2021
- First submitted
- 16 Sep 2013
- Last updated
- 24 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01945593
- Acronym / sponsor ID
- 261302
- Conditions
- Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 218 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Study start
- 15 Oct 2013 (actual)
- Primary completion
- 2 Mar 2018 (actual)
- Study completion
- 2 Mar 2018 (actual)
- First posted
- 18 Sep 2013 (estimated)
- Results
- Posted 1 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fixed BAX855 prophylaxis | Experimental | Biological: BAX85545-80 IU/kg twice weekly to once per week. |
| Pharmacokinetic (PK)-tailored BAX 855 prophylaxis | Experimental | Biological: BAX855PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- 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:
- 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.
Key exclusion criteria (25 listed)
- 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:
- 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.
- 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).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAX855Also: ADYNOVATE, BAX 855, PEGylated Recombinant Factor VIIIAntihemophilic Factor (Recombinant), PEGylated | Biological | Fixed BAX855 prophylaxis, Pharmacokinetic (PK)-tailored BAX 855 prophylaxis |
Primary outcome
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
Time frame: Baseline through end of study (53 months)
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.
Annualized Bleed Rate (ABR) - Spontaneous Bleeds
Time frame: Baseline through end of study (53 months)
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.
19 secondary outcomes
Total Annualized Bleed Rate (ABR)
Time frame: Baseline through end of study (53 months)
Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes
Time frame: Baseline through end of study (53 months)
BAX 855 Infusions Needed to Treat Bleeding Episodes
Time frame: Baseline through end of study (53 months)
Total Time Intervals Between Bleeding Episodes
Time frame: Baseline through end of study (53 months)
Average Dose of BAX 855 Per Prophylactic Infusion
Time frame: Baseline through end of study (53 months)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline through end of study (53 months)
Change From Baseline in Body Temperature
Time frame: Baseline, end of study (53 months)
Change From Baseline in Pulse Rate
Time frame: Baseline, end of study (53 months)
Change From Baseline in Respiratory Rate
Time frame: Baseline, end of study (53 months)
Change From Baseline in Blood Pressure
Time frame: Baseline, end of study (53 months)
Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.
Time frame: Baseline through end of study (53 months)
Number of Participants With Shifts in Hematology Laboratory Assessments
Time frame: Baseline through end of study (53 months)
Number of Participants With Shifts in Lipid Panel Assessments
Time frame: Baseline through end of study (53 months)
Number of Participants With Binding Antibodies
Time frame: Baseline through end of study (53 months)
Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies
Time frame: Baseline through end of study (53 months)
Change From Baseline in Bleed Severity
Time frame: Baseline, end of study (53 months)
Change From Baseline in Pain Severity
Time frame: Baseline, end of study (53 months)
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)
Time frame: 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
Time frame: Baseline, end of study (53 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
89 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BAX855 in people with Hemophilia A, run by Baxalta now part of Shire at 89 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 89 sites in United States, United Kingdom, Japan, Malaysia, South Korea and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII) (time frame: Baseline through end of study (53 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2021.