BAX 855 Continuation 261302

Principal Investigator: Hassan Yaish
Keywords: Hemophilia A , Pediatrics Department: Pediatric Administration
IRB Number: 00080547 Co Investigator: Richard Lemons
Specialty: Pediatric Hematology and Oncology
Sub Specialties: Hemophilia
Recruitment Status: Recruiting

Contact Information

Tiffanie Hales
tiffanie.hales@hsc.utah.edu
8012133367

Brief Summary

7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to continue the evaluation of the safety and efficacy of BAX 855 for prophylaxis and treatment of bleeding episodes in adult and pediatric PTPs aged ≤75 years with severe hemophilia A.
 

7.2 Primary Objectives
The co-primary objectives of the study are:
1.    To determine the safety of BAX 855 based on the incidence of FVIII inhibitory antibody
development
2.    To determine the efficacy of BAX 855 based on the annualized bleed rate (ABR) of spontaneous
bleeding episodes

7.3 Secondary Objectives
7.3.1 Efficacy
1.   To determine the total ABR (spontaneous and traumatic bleeding episodes)
2.   To determine the overall hemostatic efficacy rating of BAX 855 for treatment of breakthrough
bleeding episodes
3.   To determine the length of intervals between bleeding episodes
4.   To characterize the hemostatic efficacy of BAX 855 for treatment of bleeding episodes by the
number of BAX 855 infusions for treatment
5.   To determine total weight-adjusted consumption of BAX 855 for prophylaxis and for treatment of
bleeding episodes
6.   To assess Patient Reported Outcomes (PROs) over time for subjects receiving BAX 855

7.3.2 Safety
1. To determine the safety of BAX 855, as assessed by the occurrence of AEs and changes in vital
signs and clinical laboratory parameters
2. To determine the immunogenicity of BAX 855

7.4 Exploratory Objectives
1. To assess patient satisfaction, patient activity levels, and health resource use over time for
subjects receiving BAX 855
2. To determine the potential correlation between TGA parameters, FVIII trough
levels and ABR

Inclusion Criteria

9.1 Inclusion Criteria
9.1.1 Subjects Transitioning from Other BAX 855 Studies
Subjects 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 subjects 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.Subjects transitioning from other BAX 855 studies who meet ALL of the following
criteria are eligible for this study:
1. Subject has completed a previous BAX 855 study and is willing to immediately
transition into this continuation study.viii
2. Subject is ≤75 years of age at screening of the previous BAX 855 study.
3. Subject continues to have a Karnofsky (for subjects aged ≥ 16 years) or Lansky
(for subjects aged < 16 years) performance score of ≥ 60 (see Section 20.5).
4. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable
disease and CD4+ count ≥ 200 cells/mm3, as confirmed by central laboratory at
screening.
5. Subject is hepatitis C virus negative (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.
6. If female of childbearing potential, subject presents with a negative urine
pregnancy test and agrees to employ adequate birth control measures for the
duration of the study.
7. Subject and/or legally authorized representative is willing and able to comply
with the requirements of the protocol.


9.1.2 BAX 855 Naïve Subjects
BAX 855 naïve subjects 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 subjects who are < 12 years of age can only be enrolled in this continuation study
after enrollment in the pediatric PTP study is closed.
Enrolment of BAX 855 naïve subjects will only start once the sponsor has notified
the study sites accordingly.
BAX 855 naïve subjects who meet ALL of the following criteria are eligible for this
study:
1. Subject is ≤75 years of age at screening.
2. Subject is naïve to BAX 855.
3. Subject has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by
central laboratory at screening after at least a 72-hour washout periodix.
4. Subject aged ≥ 6 years has documented previous treatment with plasma-derived
FVIII or rFVIII for ≥ 150 EDs.
5. Subject aged < 6 years has documented previous treatment with plasma-derived
FVIII concentrates or rFVIII for ≥ 50 EDs.
6. Subject is currently receiving prophylaxis or on-demand therapy with FVIII.
7. Subject has a Karnofsky (for subjects aged ≥ 16 years) or Lansky (for subjects
aged < 16 years) performance score of ≥ 60 (see Section 20.5).
8. Subject is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm3,
as confirmed by central laboratory at screening.
9. Subject 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, subject presents with a negative urine
pregnancy test and agrees to employ adequate birth control measures for the
duration of the study.
11. Subject and/or legally authorized representative is willing and able to comply
with the requirements of the protocol.

 

 

Exclusion Criteria

9.2 Exclusion Criteria
9.2.1 Subjects Transitioning from Other BAX 855 Studies
Subjects transitioning from other BAX 855 studies who meet ANY of the following
criteria are not eligible for this study:
1. Subject had detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen
modification of the Bethesda assay) as confirmed by central laboratory at
screening.
2. Subject 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. Subject 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. Subject has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of
normal alanine aminotransferase [ALT], as confirmed by central laboratory at
screening).
5. Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as
confirmed by central laboratory at screening.
6. Subject experienced a life-threatening or gastrointestinal bleeding episode within
3 months prior to study entry.
7. Subject is scheduled to use other PEGylated drugs during study participation.
8. Subject 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. Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol
use that, in the opinion of the investigator, would affect subject safety or
compliance.
10. Subject is a family member or employee of the investigator.

9.2.2 BAX 855 Naïve Subjects
BAX 855 naïve subjects who meet ANY of the following criteria are not eligible for this
study:
1. Subject has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen
modification of the Bethesda assay) as confirmed by central laboratory at
screening.
2. Subject 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. Subject has been diagnosed with an inherited or acquired hemostatic defect other
than hemophilia A (eg, qualitative platelet defect or von Willebrand’s disease).
4. Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or
Tween 80.
5. Subject has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of
normal ALT, as confirmed by central laboratory at screening).
6. Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as
confirmed by central laboratory at screening.
7. Subject experienced a life-threatening or gastrointestinal bleeding episode within
3 months prior to study entry.
8. Subject 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. Subject 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 IP or investigational device
during the course of this study.
10. Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol
use that, in the opinion of the investigator, would affect subject safety or
compliance.
11. Subject is a family member or employee of the investigator.