Overview

This trial is active, not recruiting.

Condition hemophilia a
Treatment pegylated recombinant factor viii (rfviii)
Phase phase 3
Sponsor Baxalta US Inc.
Start date December 2013
End date December 2016
Trial size 30 participants
Trial identifier NCT01913405, 261204

Summary

The purpose of the study is to evaluate the efficacy and safety of BAX 855 in severe hemophilia A previously treated (PTP) males, 12 to 65 years of age who are undergoing elective surgical or other invasive procedures.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Pre-operative loading dose: Single loading dose, pre-surgery administered based on each study participant's individual PK results as well as target trough level for type and character of surgery, dental or invasive procedure being performed. In general, major surgery will target an 80-150% FVIII trough level, and minor surgery will target an initial 30-100% FVIII trough level. Intra-operative and post-operative dosing of BAX855 must be based on pre-dosage measurements of FVIII and the type and character of the surgery performed.
pegylated recombinant factor viii (rfviii) BAX 855

Primary Outcomes

Measure
Global Hemostatic Efficacy Assessment score (GHEA)- composed of 3 individual ratings
time frame: up to 4 weeks post discharge

Secondary Outcomes

Measure
Development of inhibitory antibodies to Factor VIII (FVIII)
time frame: Within 45 days prior to surgery (Screening visit); and End of Study Visit (4 weeks after discharge)
Development of binding antibodies to Factor VIII (FVIII), PEGylated recombinant FVIII, and polyethylene glycol (PEG)
time frame: Within 45 days prior to surgery (Screening visit); and End of Study Visit (4 weeks after discharge)
Development of anti-chinese hamster ovary (CHO) antibodies
time frame: Within 45 days prior to surgery (Screening visit); and End of Study Visit (4 weeks after discharge)
Occurrence of thrombotic events
time frame: Throughout the study period- please see Outcome Description for more details
Other investigational product (IP)-related AEs
time frame: Throughout the study period, within 45 days prior to surgery to 4 weeks after discharge (End of Study Visit)
Clinically significant changes in vital signs - Body temperature
time frame: Within 45 days prior to surgery; within 30 - 60 minutes after administration of BAX 855 for pharmacokinetics (PK); preoperatively within 2 hours of surgery; on Day 1, 3, 7 post-surgery; and during End of Study Visit (4 weeks after discharge)
Clinically significant changes in vital signs - Respiratory rate
time frame: Within 45 days prior to surgery; within 30 - 60 minutes after administration of BAX 855 for pharmacokinetics (PK); preoperatively within 2 hours of surgery; on Day 1, 3, 7 post-surgery; and during End of Study Visit (4 weeks after discharge)
Clinically significant changes in vital signs - Systolic and Diastolic Blood Pressure (BP)
time frame: Within 45 days prior to surgery; within 30 - 60 minutes after administration of BAX 855 for pharmacokinetics (PK); preoperatively within 2 hours of surgery; on Day 1, 3, 7 post-surgery; and during End of Study Visit (4 weeks after discharge)
Clinically significant changes in vital signs - Pulse Rate
time frame: Within 45 days prior to surgery; within 30 - 60 minutes after administration of BAX 855 for pharmacokinetics (PK); preoperatively within 2 hours of surgery; on Day 1, 3, 7 post-surgery; and during End of Study Visit (4 weeks after discharge)
Clinically significant changes in routine laboratory parameters- Hematology
time frame: Within 45 days prior to surgery (Screening visit); Postoperative Day 1-3 until discharge- whichever is earlier; and End of Study Visit (4 weeks after discharge)
Clinically significant changes in routine laboratory parameters - Clinical chemistry
time frame: Within 45 days prior to surgery (Screening visit); Postoperative Day 1 until discharge- whichever is earlier; and End of Study Visit (4 weeks after discharge)
Intraoperative and postoperative blood loss
time frame: Initiation of the surgery to 24 hours after completion or drain removal, if applicable
Transfusion Requirements
time frame: From initiation of the surgery to 24 hours after completion of the surgery
Bleeding Episodes
time frame: Intra- and post-operative period, until the time of discharge (minor surgery 1-3 days, major surgery average approximately 2 weeks)
Consumption of BAX855
time frame: From initiation of the surgery until the time of discharge (minor surgery 1-3 days, major surgery average approximately 2 weeks)
Development of antibodies to murine immunoglobulin G (IgG)
time frame: Within 45 days prior to surgery (Screening visit); and End of Study Visit (4 weeks after discharge)
Pharmacokinetics (PK) - Incremental recovery(IR)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Terminal half-life (T1/2)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Area under the plasma concentration/time curve from time 0 to infinity (AUC0-∞)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Mean residence time (MRT)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Clearance (CL)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Apparent volume of distribution at steady state (Vss)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours
Pharmacokinetics (PK) - Area under the plasma concentration/time curve from time 0 to 96 hours post-infusion (AUC0-96h)
time frame: Within 30 minutes pre-infusion and post-infusion at, 10 min and 0.5, 1, 3, 6, 9, 24, 32, 48, 56, 72, and 96 hours

Eligibility Criteria

Male participants from 12 years up to 65 years old.

Inclusion Criteria: - Participant requires an elective major or minor surgical, dental or other invasive procedure (e.g. biopsy, endoscopy). - Participant and/or legal representative has/have provided signed informed consent. - Participant has severe hemophilia A (Factor VIII (FVIII) level <1%) as confirmed by the central lab at screening or a documented FVIII activity level <1%. - Participant was previously treated with FVIII concentrates with ≥150 documented exposure days (EDs). - Participant is currently receiving prophylaxis or on-demand therapy with FVIII concentrate. - Participant has a Karnofsky performance score of ≥60 at screening. - Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥200 cells/mm^3, as confirmed by central laboratory at screening. - Participant 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 as assessed by the investigator. - Participant is willing and able to comply with the requirements of the study protocol. Exclusion Criteria: - Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Unit (BU) using the Nijmegen modification of the Bethesda assay) at screening as determined by the central laboratory or at any timepoint prior to screening (≥0.4 BU using the Nijmegen modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay). - History of ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC). - Participant has a platelet count <100 x 10^9/L, as confirmed by central laboratory at screening. - Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening. - Participant has severe chronic hepatic dysfunction (eg ≥5 X upper limit of normal alanine aminotransferase (ALT), as confirmed by the central laboratory at screening, or a documented International Normalized Ratio (INR) > 1.5). - Participant has a known hypersensitivity towards mouse or hamster proteins, polysorbate 80 or to PEG. - Participant is currently using or has recently (< 30 days) used pegylated drugs (other than BAX 855) prior to study participation or is scheduled to use such drugs during trial participation. - Participant is currently participating in another clinical drug (other than BAX 855) or device study or use of another investigational product or device within 30 days prior to study entry. - Participant has a diagnosis of an inherited or acquired hemostatic defect other than hemophilia A. - Participant is currently receiving, or scheduled to receive during the course of the study, an immunomodulating drug (eg, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 mg/day, or alpha interferon) other than anti-retroviral chemotherapy. - 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 safety or compliance.

Additional Information

Official title A Phase 3, Multi-Center, Open Label Study of Efficacy and Safety of PEGylated rFVIII (BAX 855) in Previously Treated Patients With Severe Hemophilia A Undergoing Surgical or Other Invasive Procedures
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Baxalta US Inc..