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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01945593




Registration number
NCT01945593
Ethics application status
Date submitted
16/09/2013
Date registered
18/09/2013
Date last updated
24/05/2021

Titles & IDs
Public title
BAX 855 Continuation
Scientific 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
Secondary ID [1] 0 0
2013-002236-24
Secondary ID [2] 0 0
261302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - BAX855

Experimental: Fixed BAX855 prophylaxis - 45-80 IU/kg twice weekly to once per week.

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


Other interventions: BAX855
Antihemophilic Factor (Recombinant), PEGylated
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
Timepoint [1] 0 0
Baseline through end of study (53 months)
Primary outcome [2] 0 0
Annualized Bleed Rate (ABR) - Spontaneous Bleeds
Timepoint [2] 0 0
Baseline through end of study (53 months)
Secondary outcome [1] 0 0
Total Annualized Bleed Rate (ABR)
Timepoint [1] 0 0
Baseline through end of study (53 months)
Secondary outcome [2] 0 0
Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes
Timepoint [2] 0 0
Baseline through end of study (53 months)
Secondary outcome [3] 0 0
BAX 855 Infusions Needed to Treat Bleeding Episodes
Timepoint [3] 0 0
Baseline through end of study (53 months)
Secondary outcome [4] 0 0
Total Time Intervals Between Bleeding Episodes
Timepoint [4] 0 0
Baseline through end of study (53 months)
Secondary outcome [5] 0 0
Average Dose of BAX 855 Per Prophylactic Infusion
Timepoint [5] 0 0
Baseline through end of study (53 months)
Secondary outcome [6] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
Baseline through end of study (53 months)
Secondary outcome [7] 0 0
Change From Baseline in Body Temperature
Timepoint [7] 0 0
Baseline, end of study (53 months)
Secondary outcome [8] 0 0
Change From Baseline in Pulse Rate
Timepoint [8] 0 0
Baseline, end of study (53 months)
Secondary outcome [9] 0 0
Change From Baseline in Respiratory Rate
Timepoint [9] 0 0
Baseline, end of study (53 months)
Secondary outcome [10] 0 0
Change From Baseline in Blood Pressure
Timepoint [10] 0 0
Baseline, end of study (53 months)
Secondary outcome [11] 0 0
Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.
Timepoint [11] 0 0
Baseline through end of study (53 months)
Secondary outcome [12] 0 0
Number of Participants With Shifts in Hematology Laboratory Assessments
Timepoint [12] 0 0
Baseline through end of study (53 months)
Secondary outcome [13] 0 0
Number of Participants With Shifts in Lipid Panel Assessments
Timepoint [13] 0 0
Baseline through end of study (53 months)
Secondary outcome [14] 0 0
Number of Participants With Binding Antibodies
Timepoint [14] 0 0
Baseline through end of study (53 months)
Secondary outcome [15] 0 0
Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies
Timepoint [15] 0 0
Baseline through end of study (53 months)
Secondary outcome [16] 0 0
Change From Baseline in Bleed Severity
Timepoint [16] 0 0
Baseline, end of study (53 months)
Secondary outcome [17] 0 0
Change From Baseline in Pain Severity
Timepoint [17] 0 0
Baseline, end of study (53 months)
Secondary outcome [18] 0 0
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)
Timepoint [18] 0 0
Baseline, end of study (53 months)
Secondary outcome [19] 0 0
Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire
Timepoint [19] 0 0
Baseline, end of study (53 months)

Eligibility
Key inclusion criteria
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.
Minimum age
No limit
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/03/2018
Sample size
Target
Accrual to date
Final
218
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Fremantle Hospital - Fremantle
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
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Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
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North Carolina
Country [10] 0 0
United States of America
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Ohio
Country [11] 0 0
United States of America
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Oklahoma
Country [12] 0 0
United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Utah
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United States of America
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Washington
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Austria
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Linz
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Austria
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Vienna
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Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Bulgaria
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Varna
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Czechia
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Brno
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Czechia
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Olomouc
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Czechia
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Praha 5
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Germany
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Niedersachsen
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Germany
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Nordrhein Westfalen
Country [26] 0 0
Germany
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Berlin
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Germany
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Hamburg
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Hong Kong
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Shatin
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Israel
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Haifa
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Israel
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Ramat-Gan
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Japan
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Aichi-Ken
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Japan
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Fukuoka-Ken
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Hiroshima-Ken
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Kanagawa-Ken
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Nara-Ken
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Tokyo-To
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Tokyo
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Busan
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Daejeon
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Korea, Republic of
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Ulsan
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Lithuania
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Vilnius
Country [44] 0 0
Malaysia
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Penang
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Malaysia
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Sarawak
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Malaysia
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Selangor
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Malaysia
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Kuala Lumpur
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Malaysia
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Pulau Pinang
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Netherlands
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Amsterdam
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Poland
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Gdansk
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Poland
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Lodz
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Romania
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Bucuresti
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Russian Federation
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Kirov
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Russian Federation
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Krasnoyarsk
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Spain
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Baleares
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Spain
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La Coruña
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Spain
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Málaga
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Spain
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Madrid
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Spain
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Valencia
Country [60] 0 0
Sweden
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Malmo
Country [61] 0 0
Sweden
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Stockholm
Country [62] 0 0
Switzerland
State/province [62] 0 0
Zuerich
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taichung
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taipei
Country [65] 0 0
Turkey
State/province [65] 0 0
Ankara
Country [66] 0 0
Turkey
State/province [66] 0 0
Antalya
Country [67] 0 0
Turkey
State/province [67] 0 0
Istanbul
Country [68] 0 0
Ukraine
State/province [68] 0 0
Donetsk
Country [69] 0 0
Ukraine
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Lviv
Country [70] 0 0
United Kingdom
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Avon
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United Kingdom
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Greater London
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United Kingdom
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Greater Manchester
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United Kingdom
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Hampshire
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United Kingdom
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Leicestershire
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United Kingdom
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West Midlands
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United Kingdom
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Baxalta now part of Shire
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Baxalta Innovations GmbH, now part of Shire
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01945593
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries