BAX 855 PK-guided Dosing

Brief Title

BAX 855 PK-guided Dosing

Official 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

Brief Summary

      1. To compare the efficacy and safety of pharmacokinetic (PK)-guided treatment with BAX 855
           targeting FVIII trough levels of 1-3% and approximately 10% (8-12%)

        2. To further characterize pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BAX
           855
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months

Secondary Outcome

 Total Annualized Bleeding Rate for Second Six Months

Condition

Hemophilia A

Intervention

PEGylated Recombinant Factor VIII

Study Arms / Comparison Groups

 Pharmacokinetic (PK) evaluation of BAX 855

Description:  Participants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

135

Start Date

November 23, 2015

Completion Date

August 5, 2018

Primary Completion Date

August 5, 2018

Eligibility 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 α-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 α-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.
      

Gender

All

Ages

12 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Study Director, , 

Location Countries

Australia

Location Countries

Australia

NCT ID

NCT02585960

Organization ID

261303

Secondary IDs

2014-005477-37

Responsible Party

Sponsor

Study Sponsor

Baxalta now part of Shire

Collaborators

 Baxalta Innovations GmbH, now part of Shire

Study Sponsor

Study Director, Study Director, Shire

Verification Date

September 2019