A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Biological: ITI
- Registration Number
- NCT02615691
- Lead Sponsor
- Baxalta now part of Shire
- Brief Summary
This study is for young children with severe hemophilia A who have previously not been treated with BAX855 or other FVIII concentrates.
The main aim of the study is to check for side effects from treatment with BAX855. This includes the buildup of antibodies against FVIII which may stop BAX855 from working properly. Another aim is to learn how well BAX855 controls bleeding.
In this study, the children can receive BAX855 either as preventative treatment (prophylaxis), or as needed to treat bleeding (on-demand).
In case a participant develops antibodies, treatment will be provided as part of the study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Previously untreated patients (PUPs) ITI Part A (Main Study): Participants age \<3 years and not experienced two joint bleeds will receive on- demand treatment of 10-80 international unit per kilogram (IU/kg) of BAX 855 intravenously depending on the severity of the bleeding episode and age \<3 years or after a maximum of two joint bleeds will receive prophylaxis treatment with dose of 25-80 IU/kg of BAX855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part A (Surgery): In participants, the administration of BAX 855 will be individualized based on the participants IR and half-life. For major surgery to achieve the target level of 80-100% FVIII in plasma of normal FVIII level and for minor surgery \>=30-60% FVIII levels for dental or other invasive surgery. Part B (Immune tolerance induction \[ITI\]): Participants will receive prophylaxis treatment of 100-200 IU/kg BAX 855 IV daily or 50 IU/kg three time in a week and will be reduced to twice weekly to maintain FVIII trough level of 1% for further 3 months. Previously untreated patients (PUPs) PEGylated Recombinant Factor VIII Part A (Main Study): Participants age \<3 years and not experienced two joint bleeds will receive on- demand treatment of 10-80 international unit per kilogram (IU/kg) of BAX 855 intravenously depending on the severity of the bleeding episode and age \<3 years or after a maximum of two joint bleeds will receive prophylaxis treatment with dose of 25-80 IU/kg of BAX855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part A (Surgery): In participants, the administration of BAX 855 will be individualized based on the participants IR and half-life. For major surgery to achieve the target level of 80-100% FVIII in plasma of normal FVIII level and for minor surgery \>=30-60% FVIII levels for dental or other invasive surgery. Part B (Immune tolerance induction \[ITI\]): Participants will receive prophylaxis treatment of 100-200 IU/kg BAX 855 IV daily or 50 IU/kg three time in a week and will be reduced to twice weekly to maintain FVIII trough level of 1% for further 3 months.
- Primary Outcome Measures
Name Time Method Number of Participants With FVIII Inhibitor Development Throughout Part A of the study, approximately 5 years Number of participants who develop an inhibitor (at any time) confirmed by a central laboratory based on a second repeat blood sample draw within 2 weeks of site notification of an inhibitor and all participants who not developed an inhibitor and has greater than or equal to (\>=) 100 exposure doses (EDs) when the sample for the last valid inhibitor test will be drawn.
Success Rate of Immune Tolerance Induction (ITI) Up to 33 months Success is defined as 1) a persistently negative inhibitor titer less than (\<) 0.6 Bethesda unit (BU), 2) FVIII IR \>=66% of the baseline value following a wash-out period of 84-96 hours, and 3) a FVIII half-life of \>=6 hours.
- Secondary Outcome Measures
Name Time Method Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Initiation of Treatment 24 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
Number of Participants With Weight-adjusted Consumption of BAX 855 Throughout Part A of the study, approximately 5 years Weight-adjusted consumption of BAX 855 will be determined based upon the record in participants diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis,surgery) and the participants weight, as measured in the clinic.
Number of Participants With Hemostatic Efficacy in Case of Surgery Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first) The hemostatic efficacy will be assessed during and after any surgical or invasive procedures, and overall as a perioperative assessment.
Half-life (T1/2) of BAX 855 Pre-infusion, Post-infusion: 15-30 minutes and 24-48 hours The Half-life to determine FVIII half-life is an optional assessment that will be performed at baseline, Visit 1, or Visit 2.
Immune Tolerance Induction (ITI) - Rate of Partial Success and Failure of ITI Up to 33 months Partial success defined as which meet two of following criteria, 1) inhibitor titer \<0.6 BU (confirmed by a central laboratory with a second blood specimen obtained within 2 months), 2) FVIII in vivo recovery \>=66% of baseline value (confirmed within a two month period), and 3) FVIII half-life \>=6 hours. Failure defined as the failure to meet the criteria for partial success.
Immune Tolerance Induction (ITI) - Annualized Bleeding Rate (ABR) Up to 33 months ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Throughout Part A and Part B of the study, approximately 7 years Clinical laboratory parameters includes hematology and clinical chemistry. Changes in laboratory values may be considered as AE if they are judged to be clinically significant.
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution From start of study treatment up to bleed resolution (approximately 5 years) 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 Bleeding Rate (ABR) for Prophylactic and On-demand Treatment Throughout Part A of the study, approximately 5 years ABR is assessed based upon each individual bleeding episode. A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (example, knee and ankle bleed following a fall) will be counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) will be reported.
Blood Loss Per Participant in Case of Surgery Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first) The intraoperative blood loss will be 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. Post-operatively, blood loss will be determined by the drainage volume collected, which will mainly consist of drainage fluid via vacuum or gravity drain, as applicable.
Immune Tolerance Induction (ITI) - Catheter-related Complications Up to 33 months The frequency per subject and per subject-year of catheter-related complications will be calculated.
Immune Tolerance Induction (ITI) - Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies Up to 33 months Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).
Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies Throughout Part A of the study, approximately 5 years Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Throughout Part A and Part B of the study, approximately 7 years An AE is defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which results in death, is life-threatening, requires inpatient hospitalization, prolongation of hospitalization, is an important medical event. Number of participants with AEs and SAEs in both part A and part B will be assessed.
Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes Throughout Part A of the study, approximately 5 years A bleeding episode is defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Incremental Recovery (IR) of BAX 855 Pre-infusion within 30 minutes; and post-infusion at 15-30 minutes and 24-48 hours BAX 855 will be administered in participants for the determination of FVIII IR at the study site at baseline and every study visit other than study visits.
Immune Tolerance Induction (ITI) - Weight-adjusted Consumption of BAX 855 for Each ITI Regimen Employed Up to 33 months Weight-adjusted consumption of BAX 855 will be determined based upon the record in participant's diaries of the actual amount of BAX 855 infused, indication (treatment of bleeding episode, prophylaxis) and the participant's weight, as measured in the clinic.
Number of Participants With Clinically Significant Changes in Vital Signs Throughout Part A and Part B of the study, approximately 7 years Vital signs will be assessed based on body temperature, respiratory rate, blood pressure, and heart rate.
Number of Infusions During Weight-adjusted Consumption of BAX 855 Throughout Part A of the study, approximately 5 years The number of BAX 855 infusions needed for each bleeding episode is determined by the participant, caregiver, clinician treating the participant, and is based upon the participant's response to treatment, using the Efficacy Rating Scale for Treatment of Bleeding Episodes.
Trial Locations
- Locations (89)
Center for Advanced Pediatrics
🇺🇸Atlanta, Georgia, United States
Hospital Ampang
🇲🇾Ampang, Kuala Lumpur, Malaysia
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
KKH
🇸🇬Singapore, Singapore
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Ann & Robert H. Lurie Children's H
🇺🇸Chicago, Illinois, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Bleeding and Clotting Dis.Inst.
🇺🇸Peoria, Illinois, United States
Kaye Edmonton Clinic
🇨🇦Edmonton, Alberta, Canada
Klinik F.Haematologie,Onkologie
🇩🇪Duesseldorf, Germany
Chinese University Of Hong Kong
ðŸ‡ðŸ‡°Shatin, Hong Kong
Essais cliniques CHU Rennes
🇫🇷Rennes cedex 09, Ille Et Vilaine, France
Rainbow Babies/Childrens Htl
🇺🇸Cleveland, Ohio, United States
Belgyogyaszat Onkohaematologia
ðŸ‡ðŸ‡ºBudapest, Hungary
Poliklinik PaediaHaematologie
🇩🇪Hamburg, Germany
Penn State MS Hershey Med Ctr
🇺🇸Hershey, Pennsylvania, United States
HUDERF
🇧🇪Bruxelles, Belgium
Univ. Ziekenhuis Gent Apotheek
🇧🇪Gent, Belgium
Rigshospitalet Copenhagen
🇩🇰Copenhagen, Denmark
Eulji University Hospital
🇰🇷Daejeon, Korea, Republic of
Hopital Jeanne de Flandre - CHU Lille
🇫🇷Lille Cedex, France
Presidio Ospedaliero F. Alessi
🇮🇹Catania, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Umberto I Pol. di Roma-Università di Roma La Sapienza
🇮🇹Rome, Italy
Akdeniz Universitesi
🇹🇷Antalya, Turkey
Istanbul Ãœniversitesi CerrahpaÅŸa
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷Izmir, Turkey
19 Mayis Universitesi
🇹🇷Samsun, Turkey
Severance Hospital, Yonsei
🇰🇷Seoul, Korea, Republic of
Royal Manchester Children's Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Inst. f. Experimentelle
🇩🇪Bonn, Germany
Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Debreceni Egyetem
ðŸ‡ðŸ‡ºDebrece, Hungary
Universitair Medisch Centrum Groningen (UMCG)
🇳🇱Groningen, Netherlands
Hospital Univ del Rio Hortega
🇪🇸Valladolid, Spain
Hospital Univ. Son Espases
🇪🇸Palma de Mallorca, Baleares, Spain
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
King Chulalongkorn Memorial
🇹ðŸ‡Patumwan, Bangkok, Thailand
Srinagarind Hospital
🇹ðŸ‡Muang, Khon Kaen, Thailand
Ramathibodi Hospital
🇹ðŸ‡Ratchathewi, Bangkok, Thailand
Siriraj Hospital
🇹ðŸ‡Bangkoknoi, Bangkok, Thailand
MI Cherkasy Reg Onc Dis of CRC
🇺🇦Cherkasy, Ukraine
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
🇺🇦Lviv, Ukraine
Erciyes Univers Tip Fakultesi
🇹🇷Kayseri, Turkey
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Hacettepe Ãœniversitesi
🇹🇷Ankara, Turkey
Hopital Necker Enfants Malades
🇫🇷Paris cedex 15, Paris, France
CHU de Rouen
🇫🇷ROUEN Cedex, France
Hospital Universitario La Paz
🇪🇸Madrid, Spain
HOSPITAL A Coruna
🇪🇸A Coruna, Spain
Werlhof-Institut GmbH
🇩🇪Hannover, Niedersachsen, Germany
Texas Tech University Health Sciences Center
🇺🇸El Paso, Texas, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
UC Davis Health System
🇺🇸Sacramento, California, United States
UMHS
🇺🇸Ann Arbor, Michigan, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Connecticut Children's Med Ctr
🇺🇸Hartford, Connecticut, United States
Kaiser Permanente Oakland M.C.
🇺🇸Roseville, California, United States
UMHAT Sv. Georgi, EAD
🇧🇬Plovdiv, Bulgaria
SHAT Oncohaematology Diseases
🇧🇬Sofia, Bulgaria
McMaster Health Science
🇨🇦Hamilton, Ontario, Canada
MHAT Sv. Marina, EAD
🇧🇬Varna, Bulgaria
Hospital Pulau Pinang
🇲🇾Georgetown, Pulau Pinang, Malaysia
Uludag Universitesi Tip Fakültesi
🇹🇷Bursa, Turkey
CI Zaporizhzhia Reg CCH of ZRC
🇺🇦Zaporizhzhia, Ukraine
Evelina Children's Hospital - St Thomas' Hospital
🇬🇧London, United Kingdom
Bristol Royal H. for Children
🇬🇧Bristol, United Kingdom
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Maharaj Nakorn Chiang Mai
🇹ðŸ‡Muang, Chiang Mai, Thailand
CHU CAEN Hopital Cote de Nacre
🇫🇷Caen cedex 9, Calvados, France
Oslo Universitetssykehus - Rikshospitalet
🇳🇴Oslo, Norway
Univ Hospital Southampton
🇬🇧Southampton, Hampshire, United Kingdom
Medizinische Universitat Wien
🇦🇹Vienna, Austria
Helsinki Univ Hospital
🇫🇮Helsinki, Finland
Hospital Sultanah Nur Zahirah
🇲🇾Terengganu, Malaysia
Kaohsiung Chung- Ho Memorial Hosp
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General
🇨🇳Taichung, Taiwan
Hospital HRPB
🇲🇾Ipoh, Perak, Malaysia
NUS YLL School of Medicine
🇸🇬Singapore, Singapore
China Medical University Hospital
🇨🇳Taichung, Taiwan
Cliniques Uni Saint-Luc
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Univ Florida College Medicine
🇺🇸Gainesville, Florida, United States
The University of Hong Kong Queen Mary Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong