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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02585960




Registration number
NCT02585960
Ethics application status
Date submitted
21/10/2015
Date registered
26/10/2015

Titles & IDs
Public title
BAX 855 PK-guided Dosing
Scientific title
Phase 3, Prospective, Randomized, Multi-center Clinical Study Comparing the Safety and Efficacy of BAX 855 Following PK-guided Prophylaxis Targeting Two Different FVIII Trough Levels in Subjects With Severe Hemophilia A
Secondary ID [1] 0 0
2014-005477-37
Secondary ID [2] 0 0
261303
Universal Trial Number (UTN)
Trial acronym
PROPEL
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
Treatment: Other - PEGylated Recombinant Factor VIII
Treatment: Other - PEGylated Recombinant Factor VIII
Treatment: Other - PEGylated Recombinant Factor VIII

Experimental: Pharmacokinetic (PK) evaluation of BAX 855 - Participants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens.

Experimental: FVIII trough target 1-3% - Standard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3%

Experimental: FVIII trough target 8-12% - Intensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12%


Treatment: Other: PEGylated Recombinant Factor VIII
Pharmacokinetic (PK) evaluation

Treatment: Other: PEGylated Recombinant Factor VIII
Standard treatment

Treatment: Other: PEGylated Recombinant Factor VIII
Intensified treatment
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months
Timepoint [1] 0 0
Day 183 to Day 364 (6 months)
Secondary outcome [1] 0 0
Total Annualized Bleeding Rate for Second Six Months
Timepoint [1] 0 0
Day 183 to Day 364 (6 months)
Secondary outcome [2] 0 0
Annualized Spontaneous Bleeding Rate for Second Six Months
Timepoint [2] 0 0
Day 183 to Day 364 (6 months)
Secondary outcome [3] 0 0
Annualized Traumatic Bleeding Rate for Second Six Months
Timepoint [3] 0 0
Day 183 to Day 364 (6 months)
Secondary outcome [4] 0 0
Annualized Joint Bleeding Rate (AJBR) for Second Six Months
Timepoint [4] 0 0
Day 183 to Day 364 (6 months)
Secondary outcome [5] 0 0
Total Weight-adjusted Consumption of BAX 855
Timepoint [5] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [6] 0 0
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions
Timepoint [6] 0 0
8 hours after study drug administration
Secondary outcome [7] 0 0
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution
Timepoint [7] 0 0
From start of study treatment up to bleed resolution (up to 12 months)
Secondary outcome [8] 0 0
Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution
Timepoint [8] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [9] 0 0
Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score
Timepoint [9] 0 0
Baseline, Month 12
Secondary outcome [10] 0 0
Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds
Timepoint [10] 0 0
Day 0 through discharge or 14 days post-surgery
Secondary outcome [11] 0 0
Blood Loss Per Participant in Case of Surgery
Timepoint [11] 0 0
Day 0 through discharge or 14 days post-surgery
Secondary outcome [12] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [12] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [13] 0 0
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Related Adverse Events
Timepoint [13] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [14] 0 0
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events
Timepoint [14] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [15] 0 0
Number of Participants With Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein
Timepoint [15] 0 0
From start of study treatment up to 12 months (completion or termination)
Secondary outcome [16] 0 0
Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey
Timepoint [16] 0 0
Baseline, Month 12 (completion or termination)
Secondary outcome [17] 0 0
Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf)
Timepoint [17] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [18] 0 0
Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855
Timepoint [18] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [19] 0 0
Plasma Half-life (T1/2) of BAX 855
Timepoint [19] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [20] 0 0
Mean Residence Time (MRT) of BAX 855
Timepoint [20] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [21] 0 0
Maximum Plasma Concentration (Cmax) of BAX 855
Timepoint [21] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [22] 0 0
Time to Maximum Concentration of BAX 855 in Plasma (Tmax)
Timepoint [22] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [23] 0 0
Total Body Clearance (CL) of BAX 855
Timepoint [23] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [24] 0 0
Volume of Distribution at Steady State (Vss)
Timepoint [24] 0 0
Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Secondary outcome [25] 0 0
Incremental Recovery (IR) Over Time
Timepoint [25] 0 0
Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination)

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

* Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study:

1. Participant has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Baxalta Continuation Study 261302.
2. Participant is either receiving on-demand treatment or prophylactic treatment with BAX 855 and had an Annual Bleed Rate (ABR) of = 2 documented and treated during the past 12 months.
3. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count = 200 cells/mm^3, as confirmed by central laboratory.
4. Participant is willing and able to comply with the requirements of the protocol.
* Newly recruited participants (ie not transitioning from another BAX 855 study) including BAX855 naïve participants who meet ALL of the following criteria are eligible for this study:

1. Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory OR by historically documented FVIII clotting activity performed by a certified clinical laboratory, optionally supported by a FVIII gene mutation consistent with severe hemophilia A
2. Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for = 150 documented exposure days (EDs)
3. Participant is either receiving on-demand treatment or prophylactic treatment and had an annual bleeding rate of = 2 documented and treated during the past 12 months.
4. Participant has a Karnofsky performance score of = 60 at screening
5. Participant is HIV-; or HIV+ with stable disease and CD4+ count = 200 cells/mm^3, as confirmed by central laboratory at screening
6. Participant is hepatitis C virus negative (HCV-) by antibody (if positive, additional PCR testing will be performed), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis
7. 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
8. Participant is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERIA:

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

1. Participant has developed a confirmed inhibitory antibody to FVIII with a titer of = 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at the central laboratory during the course of the previous BAX 855 study.
2. Participant has been diagnosed with an acquired hemostatic defect other than hemophilia A.
3. The participant's weight is < 35 kg or > 100 kg.
4. Participant's platelet count is < 100,000/mL.
5. Participant has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal).
6. Participant has active hepatic disease with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels = 5 times the upper limit of normal.
7. Participant is scheduled to receive a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy during the study.
8. Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant's safety or compliance.
9. Participant is planning to take part in any other clinical study during the course of the study.
10. Participant is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.

Newly recruited participants (ie not transitioning from another BAX 855 study) 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 a history of confirmed FVIII inhibitors with a titer = 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed with the respective cut-off in the local laboratory) 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. The participant's weight is < 35 kg or > 100 kg.
5. Participant's platelet count is < 100,000/mL.
6. Participant has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80.
7. Participant has severe chronic hepatic dysfunction [eg, = 5 times upper limit of normal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as confirmed by central laboratory at screening, or a documented INR > 1.5].
8. Participant has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal).
9. Participant has current or recent (< 30 days) use of other pegylated drugs prior to study participation or is scheduled to use such drugs during study participation.
10. Participant is scheduled to receive during the course of the study, a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral chemotherapy.
11. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
12. Participant has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
13. Participant is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
Minimum age
12 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled 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
23/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/08/2018
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Royal Brisbane Women's Hospital - Herston
Recruitment hospital [2] 0 0
The Perth Blood Institute - Nedlands
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Austria
State/province [13] 0 0
Vienna
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Plovdiv
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Varna
Country [17] 0 0
France
State/province [17] 0 0
Alpes Maritimes
Country [18] 0 0
France
State/province [18] 0 0
Finistere
Country [19] 0 0
France
State/province [19] 0 0
Ille Et Vilaine
Country [20] 0 0
France
State/province [20] 0 0
Caen
Country [21] 0 0
France
State/province [21] 0 0
Rouen
Country [22] 0 0
Germany
State/province [22] 0 0
Hessen
Country [23] 0 0
Germany
State/province [23] 0 0
Nordrhein Westfalen
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Leipzig
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
Hong Kong
State/province [27] 0 0
Shatin
Country [28] 0 0
Hungary
State/province [28] 0 0
Budapest
Country [29] 0 0
Hungary
State/province [29] 0 0
Debrecen
Country [30] 0 0
Hungary
State/province [30] 0 0
Pecs
Country [31] 0 0
Israel
State/province [31] 0 0
Tel-Hashomer
Country [32] 0 0
Italy
State/province [32] 0 0
Treviso
Country [33] 0 0
Italy
State/province [33] 0 0
Catania
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
Country [35] 0 0
Italy
State/province [35] 0 0
Roma
Country [36] 0 0
Italy
State/province [36] 0 0
Torino
Country [37] 0 0
Italy
State/province [37] 0 0
Vicenza
Country [38] 0 0
Malaysia
State/province [38] 0 0
Kuala Lumpur
Country [39] 0 0
Malaysia
State/province [39] 0 0
Sabah
Country [40] 0 0
Malaysia
State/province [40] 0 0
Melaka
Country [41] 0 0
Malaysia
State/province [41] 0 0
Pulau Pinang
Country [42] 0 0
Norway
State/province [42] 0 0
Oslo
Country [43] 0 0
Poland
State/province [43] 0 0
Lodz
Country [44] 0 0
Poland
State/province [44] 0 0
Poznan
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Poland
State/province [46] 0 0
Wroclaw
Country [47] 0 0
Romania
State/province [47] 0 0
Brasov
Country [48] 0 0
Romania
State/province [48] 0 0
Cluj Napoca
Country [49] 0 0
Singapore
State/province [49] 0 0
Singapore
Country [50] 0 0
Spain
State/province [50] 0 0
Baleares
Country [51] 0 0
Spain
State/province [51] 0 0
La Coruña
Country [52] 0 0
Spain
State/province [52] 0 0
Málaga
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Sweden
State/province [54] 0 0
Gothenburg
Country [55] 0 0
Sweden
State/province [55] 0 0
Stockholm
Country [56] 0 0
Switzerland
State/province [56] 0 0
Zürich
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taichung
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taipei
Country [59] 0 0
Turkey
State/province [59] 0 0
Adana
Country [60] 0 0
Turkey
State/province [60] 0 0
Antalya
Country [61] 0 0
Turkey
State/province [61] 0 0
Istanbul
Country [62] 0 0
Turkey
State/province [62] 0 0
Izmir
Country [63] 0 0
Ukraine
State/province [63] 0 0
Kyiv
Country [64] 0 0
Ukraine
State/province [64] 0 0
Lviv
Country [65] 0 0
Ukraine
State/province [65] 0 0
Poltava
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Avon
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Greater London
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Greater Manchester
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Hampshire
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Leicestershire
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Oxfordshire
Country [72] 0 0
United Kingdom
State/province [72] 0 0
West Glamorgan

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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02585960