BAX 855 PK-guided Dosing

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02585960
• Date of registration: 21/10/2015
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: BAX 855 PK-guided Dosing PROPEL
• 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
• Date of first enrolment: November 23, 2015
• Target sample size: 135
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02585960
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Bulgaria, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Malaysia, Norway, Poland, Romania, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion 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


Age minimum: 12 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hemophilia A

Intervention(s)

Biological: PEGylated Recombinant Factor VIII

Primary Outcome(s)

Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months [Time Frame: Day 183 to Day 364 (6 months)]

Secondary Outcome(s)

Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution [Time Frame: From start of study treatment up to bleed resolution (up to 12 months)]

Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf) [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds [Time Frame: Day 0 through discharge or 14 days post-surgery]

Annualized Joint Bleeding Rate (AJBR) for Second Six Months [Time Frame: Day 183 to Day 364 (6 months)]

Annualized Spontaneous Bleeding Rate for Second Six Months [Time Frame: Day 183 to Day 364 (6 months)]

Time to Maximum Concentration of BAX 855 in Plasma (Tmax) [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score [Time Frame: Baseline, Month 12]

Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions [Time Frame: 8 hours after study drug administration]

Total Body Clearance (CL) of BAX 855 [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Volume of Distribution at Steady State (Vss) [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Mean Residence Time (MRT) of BAX 855 [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Blood Loss Per Participant in Case of Surgery [Time Frame: Day 0 through discharge or 14 days post-surgery]

Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey [Time Frame: Baseline, Month 12 (completion or termination)]

Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855 [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Related Adverse Events [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Annualized Traumatic Bleeding Rate for Second Six Months [Time Frame: Day 183 to Day 364 (6 months)]

Incremental Recovery (IR) Over Time [Time Frame: Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination)]

Total Weight-adjusted Consumption of BAX 855 [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Maximum Plasma Concentration (Cmax) of BAX 855 [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

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 [Time Frame: From start of study treatment up to 12 months (completion or termination)]

Plasma Half-life (T1/2) of BAX 855 [Time Frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion]

Total Annualized Bleeding Rate for Second Six Months [Time Frame: Day 183 to Day 364 (6 months)]

Secondary ID(s)

2014-005477-37

261303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Baxalta Innovations GmbH, now part of Shire

Results

• Results available: Yes
• Date Posted: 26/08/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02585960