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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01736475




Registration number
NCT01736475
Ethics application status
Date submitted
21/11/2012
Date registered
29/11/2012

Titles & IDs
Public title
Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study)
Scientific title
A Phase 2/3, Multi-Center, Open Label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prophylaxis and Treatment of Bleeding in Previously Treated Patients With Severe Hemophilia A
Secondary ID [1] 0 0
2012-003599-38
Secondary ID [2] 0 0
261201
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
Treatment: Other - Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
Treatment: Other - PEGylated Recombinant Factor VIII
Treatment: Other - PEGylated Recombinant Factor VIII
Treatment: Other - PEGylated Recombinant Factor VIII

Experimental: Prophylaxis -

Experimental: On-demand -


Treatment: Other: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
Pharmacokinetic (PK) evaluation of ADVATE

Treatment: Other: PEGylated Recombinant Factor VIII
Pharmacokinetic (PK) evaluation of BAX 855

Treatment: Other: PEGylated Recombinant Factor VIII
Prophylaxis treatment

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

Outcomes
Primary outcome [1] 0 0
Annualized Bleeding Rate (ABR)
Timepoint [1] 0 0
9 months
Secondary outcome [1] 0 0
Rate of Success of BAX 855 for Treatment of Bleeding Episodes
Timepoint [1] 0 0
At least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm.
Secondary outcome [2] 0 0
Average Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes
Timepoint [2] 0 0
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Secondary outcome [3] 0 0
Number of Participants With =1, 2, 3, 4, 5, 6, or >6 Month Time Intervals Between Bleeding Episodes or no Bleeding Episodes
Timepoint [3] 0 0
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Secondary outcome [4] 0 0
Weight-adjusted Consumption of BAX 855 - Per Prophylactic Infusion and Pharmacokinetic (PK) Infusion
Timepoint [4] 0 0
Prophylactic Infusion: =50 exposure days or 6 months (±2 weeks), whichever occurs last. PK Infusion: PK #1 Pre-infusion within 30 minutes; Post-infusion 10 min, and 0.5, 1, 3, 6, 24, 32, 48, 56 hours (h). PK #2 also at Post-infusion 96h
Secondary outcome [5] 0 0
Weight-adjusted Consumption of BAX 855 - Per Treatment of Bleeding Episode (BE) and Per BE for Maintenance of Hemostasis
Timepoint [5] 0 0
Treatment of Bleeding Episode (BE): Minor/Moderate BE every 12 to 24 hours until bleeding is resolved; Major BE every 8 to 12 hours until bleeding is resolved. Per BE for Maintenance of Hemostasis: within 48 hours after bleeding episode resolution.
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events
Timepoint [6] 0 0
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Secondary outcome [7] 0 0
Immunogenicity - Number of Participants With Positive Inhibitory Antibodies to FVIII, Binding Antibodies to FVIII, PEG-VIII, PEG and Anti-CHO Antibodies at Study Completion/Termination
Timepoint [7] 0 0
From first exposure to BAX 855 until the end of the study, [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm; and 6 months (± 2 weeks) for the on-demand arm].
Secondary outcome [8] 0 0
Patient Reported Outcomes: Haemo-SYM Questionnaire, Change in Score From Baseline to End of Study
Timepoint [8] 0 0
Baseline; and end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
Secondary outcome [9] 0 0
Patient Reported Outcomes - Short Form (SF)-36, Change From Baseline to End of Study
Timepoint [9] 0 0
Baseline; and end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm]
Secondary outcome [10] 0 0
Pharmacokinetics (Pk) - Plasma Half-life (One-stage Clotting Assay)
Timepoint [10] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [11] 0 0
Pharmacokinetics (Pk) - Mean Residence Time (One-stage Clotting Assay)
Timepoint [11] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [12] 0 0
Pharmacokinetics (Pk) - Total Body Clearance (One-stage Clotting Assay)
Timepoint [12] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [13] 0 0
Pharmacokinetics (Pk) - Incremental Recovery Over Time (One-stage Clotting Assay)
Timepoint [13] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [14] 0 0
Pharmacokinetics (Pk) - Area Under the Concentration Versus Time Curve From 0 to Infinity (AUC0-8) (One-stage Clotting Assay)
Timepoint [14] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [15] 0 0
Pharmacokinetics (Pk) - Apparent Volume of Distribution at Steady State (Vss) (One-stage Clotting Assay)
Timepoint [15] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [16] 0 0
Pharmacokinetics (Pk) - Maximum Plasma Concentration (Cmax) (One-stage Clotting Assay)
Timepoint [16] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [17] 0 0
Pharmacokinetics (Pk) -Time to Maximum Concentration in Plasma (Tmax) (One-stage Clotting Assay)
Timepoint [17] 0 0
Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
Secondary outcome [18] 0 0
Change in Vital Signs From Screening - Temperature
Timepoint [18] 0 0
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Secondary outcome [19] 0 0
Change in Vital Signs From Screening - Pulse Rate
Timepoint [19] 0 0
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Secondary outcome [20] 0 0
Change in Vital Signs From Screening - Respiratory Rate
Timepoint [20] 0 0
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Secondary outcome [21] 0 0
Changes in Vital Signs From Screening - Blood Pressure
Timepoint [21] 0 0
Screening, week 2, week 4, exposure day 10-15, month 3, study completion/termination
Secondary outcome [22] 0 0
Changes in Clinical Chemistry Laboratory Assessments From Screening - Albumin and Protein
Timepoint [22] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [23] 0 0
Changes in Clinical Chemistry Laboratory Assessments From Screening - Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase
Timepoint [23] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [24] 0 0
Changes in Clinical Chemistry Laboratory Assessments From Screening - Bicarbonate, Chloride, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN)
Timepoint [24] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [25] 0 0
Changes in Clinical Chemistry Laboratory Assessments From Screening - Creatinine, and Bilirubin
Timepoint [25] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [26] 0 0
Changes in Hematology Laboratory Assessments From Screening - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes
Timepoint [26] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [27] 0 0
Changes in Hematology Laboratory Assessments From Screening - Hematocrit
Timepoint [27] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [28] 0 0
Changes in Hematology Laboratory Assessments From Screening - Hemoglobin
Timepoint [28] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [29] 0 0
Changes in Hematology Laboratory Assessments From Screening - Erythrocytes
Timepoint [29] 0 0
Screening, week 2, week 4, month 3, study completion/termination
Secondary outcome [30] 0 0
Changes in Lipid Panel Assessments From Screening - Cholesterol; High Density Lipoprotein (HDL); Low Density Lipoprotein (LDL); Triglycerides; and Very Low Density Lipoprotein (VLDL)
Timepoint [30] 0 0
Screening, week 2, week 4, month 3, study completion/termination

Eligibility
Key inclusion criteria
Main

* Participant and/or legal representative has/have voluntarily provided signed informed consent
* Participant is 12 to 65 years old at the time of screening
* Participant is male with severe hemophilia A (Factor VIII (FVIII) clotting activity < 1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity <1%
* Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for =150 documented exposure days (EDs)
* Participant is currently receiving prophylaxis or on-demand therapy with FVIII
* Participant is willing and able to comply with the requirements of the protocol

Main
Minimum age
12 Years
Maximum age
65 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has detectable FVIII inhibitory antibodies (= 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
* Participant has history of FVIII inhibitory antibodies (= 0.4 BU using the Nijmegen modification of the Bethesda assay or = 0.6 BU using 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).

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 2
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
31/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/07/2014
Sample size
Target
Accrual to date
Final
159
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 - Clayton
Recruitment hospital [3] 0 0
Fremantle Hospital - Fremantle
Recruitment hospital [4] 0 0
Hollywood Specialist Centre - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6160 - Fremantle
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
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
State/province [6] 0 0
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
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Austria
State/province [15] 0 0
Linz
Country [16] 0 0
Austria
State/province [16] 0 0
Vienna
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Czechia
State/province [18] 0 0
Brno
Country [19] 0 0
Czechia
State/province [19] 0 0
Olomouc
Country [20] 0 0
Czechia
State/province [20] 0 0
Praha 5
Country [21] 0 0
Germany
State/province [21] 0 0
Nordrhein Westfalen
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Hamburg
Country [24] 0 0
Germany
State/province [24] 0 0
Hannover
Country [25] 0 0
Israel
State/province [25] 0 0
Haifa
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Aviv
Country [27] 0 0
Japan
State/province [27] 0 0
Aichi-Ken
Country [28] 0 0
Japan
State/province [28] 0 0
Fukuoka-Ken
Country [29] 0 0
Japan
State/province [29] 0 0
Hiroshima-Ken
Country [30] 0 0
Japan
State/province [30] 0 0
Hyogo-Ken
Country [31] 0 0
Japan
State/province [31] 0 0
Kanagawa-Ken
Country [32] 0 0
Japan
State/province [32] 0 0
Nara-Ken
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo-To
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Jeollanam-do
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Busan
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Daejeon
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Ulsan
Country [39] 0 0
Lithuania
State/province [39] 0 0
Vilnius
Country [40] 0 0
Malaysia
State/province [40] 0 0
Pulau Pinang
Country [41] 0 0
Malaysia
State/province [41] 0 0
Selangor
Country [42] 0 0
Malaysia
State/province [42] 0 0
Kuala Lumpur
Country [43] 0 0
Netherlands
State/province [43] 0 0
Amsterdam
Country [44] 0 0
Poland
State/province [44] 0 0
Gdansk
Country [45] 0 0
Poland
State/province [45] 0 0
Lodz
Country [46] 0 0
Romania
State/province [46] 0 0
Bucuresti
Country [47] 0 0
Spain
State/province [47] 0 0
Baleares
Country [48] 0 0
Spain
State/province [48] 0 0
La Coruña
Country [49] 0 0
Spain
State/province [49] 0 0
Málaga
Country [50] 0 0
Spain
State/province [50] 0 0
Valencia
Country [51] 0 0
Sweden
State/province [51] 0 0
Malmö
Country [52] 0 0
Sweden
State/province [52] 0 0
Stockholm
Country [53] 0 0
Switzerland
State/province [53] 0 0
Zurich
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei
Country [55] 0 0
Ukraine
State/province [55] 0 0
Donetsk
Country [56] 0 0
Ukraine
State/province [56] 0 0
Lviv
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Avon
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Greater London
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Greater Manchester
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Leicestershire
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Oxfordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Baxalta now part of Shire
Address
Country

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01736475