BAX 855 PK-guided Dosing
- Conditions
- Hemophilia A
- Interventions
- Biological: PEGylated Recombinant Factor VIII
- Registration Number
- NCT02585960
- Lead Sponsor
- Baxalta now part of Shire
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 135
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FVIII trough target 1-3% PEGylated Recombinant Factor VIII Standard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3% FVIII trough target 8-12% PEGylated Recombinant Factor VIII Intensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12% Pharmacokinetic (PK) evaluation of BAX 855 PEGylated Recombinant Factor VIII Participants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens.
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months Day 183 to Day 364 (6 months) Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
- Secondary Outcome Measures
Name Time Method 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 From start of study treatment up to 12 months (completion or termination) Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein were reported here.
Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf) Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion Area under the plasma concentration versus time curve from time 0 to infinity of BAX 855 were reported.
Mean Residence Time (MRT) of BAX 855 Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion MRT of BAX 855 were reported.
Incremental Recovery (IR) Over Time Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination) Incremental recovery was calculated by BAX 855 increment (IU/dL) / BAX 855 dose (IU/kg).
Annualized Traumatic Bleeding Rate for Second Six Months Day 183 to Day 364 (6 months) Annualized traumatic bleeding rate was determined by dividing the number of traumatic bleeds by observation period in years. A bleed was defined as traumatic if it was related to injury/trauma.
Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution From start of study treatment up to 12 months (completion or termination) Infusions of BAX 855 that were required until bleed resolution were reported.
Total Weight-adjusted Consumption of BAX 855 From start of study treatment up to 12 months (completion or termination) Total weight-adjusted consumption of BAX 855 were reported.
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Related Adverse Events From start of study treatment up to 12 months (completion or termination) Vital signs included systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature.
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions 8 hours after study drug administration The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Annualized Spontaneous Bleeding Rate for Second Six Months Day 183 to Day 364 (6 months) Annualized spontaneous bleeding rate was determined by dividing the number of spontaneous bleeds by observation period in years. A bleed was defined as spontaneous if it was not related to injury/trauma.
Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score Baseline, Month 12 HJHS was assessed based on the following components of the elbow, knee, and ankle joints: swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength, together with an assessment of the global gait. The HJHS is a validated 11-item scoring tool based on radiologic and clinical evaluation, sensitive to detect early signs and minor changes. HJHS ranges from 0 to 124. Higher values in the HJHS represent worse situation for the participant.
Plasma Half-life (T1/2) of BAX 855 Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion T1/2 of BAX 855 in plasma were reported.
Volume of Distribution at Steady State (Vss) Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion Volume of distribution was defined as the theoretical volume in which the total amount of drug was uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate.
Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds Day 0 through discharge or 14 days post-surgery The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens. Hemostatic efficacy was evaluated intra-operatively (from start to end of the procedure), post-operatively (from the end of procedure up to 24 h post procedure), and perioperatively (from the start of procedure to participant discharge from hospital or 14 days after completion of procedure; whichever was first).
Blood Loss Per Participant in Case of Surgery Day 0 through discharge or 14 days post-surgery The intraoperative blood loss was measured by determining the volume of blood and fluid removal through suction into the collection container (waste box and/or cell saver) and the estimated blood loss into swabs and towels during the procedure, per the anesthesiologist's record. Postoperatively, blood loss was determined by the drainage volume collected, which mainly consisted of drainage fluid via vacuum or gravity drain, as applicable. In cases where no drain was present, blood loss was determined by the surgeon's clinical judgment, as applicable or entered as "not available". Blood loss was evaluated intra-operatively (from start to end of the procedure), post-operatively (from the end of procedure up to 24 h post procedure), and perioperatively (from the start of procedure to participant discharge from hospital or 14 days after completion of procedure; whichever was first).
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events From start of study treatment up to 12 months (completion or termination) Clinical laboratory assessments included clinical chemistry, hematology, lipid panel, genetics, T-cell, B-cell and NK cell (TBNK) and viral serology.
Total Annualized Bleeding Rate for Second Six Months Day 183 to Day 364 (6 months) Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Annualized Joint Bleeding Rate (AJBR) for Second Six Months Day 183 to Day 364 (6 months) Annualized joint bleeding rate was determined by dividing the number of joint bleeds by observation period in years. An acute joint bleed include some or all of the following: 'aura', pain, swelling, warmth of the skin over the joint, decreased range of motion and difficulty in using the limb compared with baseline or loss of function.
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution From start of study treatment up to bleed resolution (up to 12 months) The participant or caregiver rated the overall treatment response using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.
Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey Baseline, Month 12 (completion or termination) Short Form (36) Health Survey (SF-36) is a 36-item validated, generic health related quality of life (HR QoL) instrument. PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both sub-scores and summary scores.
Maximum Plasma Concentration (Cmax) of BAX 855 Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion Cmax of BAX 855 were reported.
Time to Maximum Concentration of BAX 855 in Plasma (Tmax) Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion Tmax of BAX 855 were reported.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From start of study treatment up to 12 months (completion or termination) An AE was any unfavorable and unintended sign (an abnormal laboratory finding), symptom (rash, pain, discomfort, fever, dizziness, etc.), disease (peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an investigational product (IP), whether or not considered causally related to the IP. A SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/results in death, life-threatening, required in-patient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event that was not immediately life-threatening or resulted in death or required hospitalization but jeopardize the participant or required medical or surgical intervention to prevent any of the above outcomes.
Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855 Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion IR at Cmax of BAX 855 were reported.
Total Body Clearance (CL) of BAX 855 Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion Total body clearance of BAX 855 from blood by the kidney were reported.
Trial Locations
- Locations (83)
Royal Brisbane Women's Hospital
🇦🇺Herston, Queensland, Australia
Gulf States Hemophilia Centre
🇺🇸Houston, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
AKH - Medizinische Universität Wien
🇦🇹Vienna, Austria
CHU Nice- Service hematologie
🇫🇷Nice, Alpes Maritimes, France
Hôpital Morvan
🇫🇷Brest Cedex, Finistere, France
COAGULATION RESEARCH CENTRE GmbH
🇩🇪Duisburg, Nordrhein Westfalen, Germany
MVZ Labor Dr. Reising-Ackermann
🇩🇪Leipzig, Germany
UOC Ematologia, Azienda ULSS 8 Asolo, Regione Veneto
🇮🇹Castelfranco Veneto, Treviso, Italy
Umberto I Pol. di Roma-Università di Roma La Sapienza
🇮🇹Roma, Italy
Fondazione Policlinico Universitario A. Gemelli
🇮🇹Roma, Italy
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Alvamed
🇵🇱Poznań, Poland
University of Utah
🇺🇸Salt Lake City, Utah, United States
The Perth Blood Institute
🇦🇺Nedlands, Western Australia, Australia
University of Colorado
🇺🇸Aurora, Colorado, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Arizona Hemophilia & Thrombosis Center, located within The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Emory University-ECC
🇺🇸Atlanta, Georgia, United States
University of Louisville KCPCRU
🇺🇸Louisville, Kentucky, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
UMHAT "Sv. Georgi", EAD
🇧🇬Plovdiv, Bulgaria
CHU Charles Nicolle
🇫🇷Rouen, France
MHAT 'Sv. Marina', EAD, Clinic of Clinical Hematology
🇧🇬Varna, Bulgaria
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
🇧🇬Sofia, Bulgaria
CHU de Caen - Hôpital Côte de Nacre
🇫🇷Caen, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, Ille Et Vilaine, France
HZRM Hamophilie Zentrum Rhein Main GmbH
🇩🇪Mörfelden-Walldorf, Hessen, Germany
Inst. f. Experimentelle Hamatologie u. Transfusionsmedizin
🇩🇪Bonn, Nordrhein Westfalen, Germany
Hamophiliezentrum/Gerinnungssprechstunde
🇩🇪Berlin, Germany
PTE ÁOK
🇭🇺Pecs, Hungary
Magyar Honvedseg EK
🇭🇺Budapest, Hungary
DE OEC Belgyógyászati Int
🇭🇺Debrecen, Hungary
Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
Presidio Osped. Ferrarotto
🇮🇹Catania, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
AOU Citta della Salute e della Scienza - Presidio Molinette
🇮🇹Torino, Italy
ULSS n. 6 "Vicenza"
🇮🇹Vicenza, Italy
Hospital Ampang
🇲🇾Ampang, Kuala Lumpur, Malaysia
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Oslo Universitetssykehus HF
🇳🇴Oslo, Norway
Hospital Melaka
🇲🇾Melaka, Malaysia
Instytut Hematologii Ii Transfuzjologii
🇵🇱Warszawa, Poland
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Sabah, Malaysia
SP Szpital Kliniczny Nr 1 we Wroclawiu
🇵🇱Wroclaw, Poland
Wojewodzki Szpital Specjalistyczny im. Mikolaja Kopernika, Klinika Hematologii
🇵🇱Lodz, Poland
Institutul Oncologic ClNa.
🇷🇴Cluj Napoca, Romania
Spitalul Clinic Judetean de Urgenta Brasov
🇷🇴Brasov, Romania
National University Hospital
🇸🇬Singapore, Singapore
Singapore General Hospital- Parent
🇸🇬Singapore, Singapore
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, La Coruña, Spain
KK Women's And Children's Hospital
🇸🇬Singapore, Singapore
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Málaga, Spain
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Baleares, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Gothenburg, Sweden
Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Istanbul University
🇹🇷Istanbul, Turkey
Acibadem Hastanesi
🇹🇷Adana, Turkey
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Akdeniz University
🇹🇷Antalya, Turkey
Ege University
🇹🇷Izmir, Turkey
NChSH Okhmatdyt of MoHU Center of Children Oncohematology and Bone Marrow Transplantation
🇺🇦Kyiv, Ukraine
Kyiv CCH #9 Dept of Surgery City SPC of Diagnostics & Treatment of Patients with HP
🇺🇦Kyiv, Ukraine
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
🇺🇦Lviv, Ukraine
M.V. Sklifosovskyi Poltava RCH Dept of Gematology HSEIU Ukrainian Medical Stomatological Academy
🇺🇦Poltava, Ukraine
Bristol Royal Hospital for Children
🇬🇧Bristol, Avon, United Kingdom
Royal Free Hospital
🇬🇧London, Greater London, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, Leicestershire, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, West Glamorgan, United Kingdom
Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong