Hemophilia APhase 3PROPELNCT02585960
BAX 855 PK-guided Dosing
A Phase 3 study testing PEGylated Recombinant Factor VIII in people with Hemophilia A, run by Baxalta now part of Shire at 83 sites in 22 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Hemophilia A
- What is being tested?
- PEGylated Recombinant Factor VIII
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 83 sitesin 22 countries
- Study dates
- 23 Nov 2015to 5 Aug 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study:
- Participant has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Baxalta Continuation Study 261302.
- 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.
- Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory.
- 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:
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- 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
- Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥ 150 documented exposure days (EDs)
- 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.
- Participant has a Karnofsky performance score of ≥ 60 at screening
- Participant is 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 (if positive, additional PCR testing will be performed), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis
- 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
- Participant is willing and able to comply with the requirements of the protocol.
Who cannot join
- Participants transitioning from another BAX 855 study who meet ANY of the following criteria are not eligible for this study:
- 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.
- Participant has been diagnosed with an acquired hemostatic defect other than hemophilia A.
- The participant's weight is < 35 kg or > 100 kg.
- Participant's platelet count is < 100,000/mL.
- Participant has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal).
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- Participant has active hepatic disease with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ 5 times the upper limit of normal.
- 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.
- 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.
- Participant is planning to take part in any other clinical study during the course of the study.
- 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:
- Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
- 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.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
- The participant's weight is < 35 kg or > 100 kg.
- Participant's platelet count is < 100,000/mL.
- Participant has known hypersensitivity towards mouse or hamster proteins, PEG or Tween 80.
- 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].
- Participant has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal).
- 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.
- 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.
- 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.
- 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.
- 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.
Trial locations and contacts
83 sites in 22 countries.
83 sites in 22 countries
United States14 sites
Emory University-ECC
Atlanta, Georgia, 30322
University of Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Florida College of Medicine
Gainesville, Florida, 32610
Gulf States Hemophilia Centre
Houston, Texas, 77030
University of Kentucky Medical Center
Lexington, Kentucky, 40504
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Louisville KCPCRU
Louisville, Kentucky, 40202
Tulane University
New Orleans, Louisiana, 70112
University of Nebraska Medical Center
Omaha, Nebraska, 68198-5456
Phoenix Childrens Hospital
Phoenix, Arizona, 85016-7710
University of Utah
Salt Lake City, Utah, 84132
University of Washington
Seattle, Washington, 98104
Arizona Hemophilia & Thrombosis Center, located within The University of Arizona Cancer Center
Tucson, Arizona, 85724
Italy7 sites
UOC Ematologia, Azienda ULSS 8 Asolo, Regione Veneto
Castelfranco Veneto, Treviso, 31033
Presidio Osped. Ferrarotto
Catania, 90124
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Umberto I Pol. di Roma-Università di Roma La Sapienza
Roma, 00144
Fondazione Policlinico Universitario A. Gemelli
Roma, 00168
AOU Citta della Salute e della Scienza - Presidio Molinette
Torino, 10126
ULSS n. 6 "Vicenza"
Vicenza, 36100
United Kingdom7 sites
Bristol Royal Hospital for Children
Bristol, Avon, BS2 8BJ
University Hospital of Wales
Cardiff, West Glamorgan, CF14 4XN
Leicester Royal Infirmary
Leicester, Leicestershire, LE1 5WW
Royal Free Hospital
London, Greater London, NW3 2QG
Royal Manchester Children's Hospital
Manchester, Greater Manchester, M13 9WL
Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
Southampton General Hospital
Southampton, Hampshire, SO16 6YD
France5 sites
Hôpital Morvan
Brest, Finistere, 29609
CHU de Caen - Hôpital Côte de Nacre
Caen, 14003
CHU Nice- Service hematologie
Nice, Alpes Maritimes, 06200
CHU Rennes - Hopital Pontchaillou
Rennes, Ille Et Vilaine, 35033
CHU Charles Nicolle
Rouen, 76031
Germany5 sites
Hamophiliezentrum/Gerinnungssprechstunde
Berlin, 10249
Inst. f. Experimentelle Hamatologie u. Transfusionsmedizin
Bonn, North Rhine-Westphalia, 53127
COAGULATION RESEARCH CENTRE GmbH
Duisburg, North Rhine-Westphalia, 47051
MVZ Labor Dr. Reising-Ackermann
Leipzig, 04289
HZRM Hamophilie Zentrum Rhein Main GmbH
Mörfelden-Walldorf, Hesse, 65446
Malaysia5 sites
Hospital Ampang
Ampang, Kuala Lumpur, 68000
Hospital Queen Elizabeth
Kota Kinabalu, Sabah, 88586
Hospital Kuala Lumpur
Kuala Lumpur, 50586
Hospital Melaka
Malacca, 75400
Hospital Pulau Pinang
Pulau Pinang, 10450
Poland4 sites
Wojewodzki Szpital Specjalistyczny im. Mikolaja Kopernika, Klinika Hematologii
Lodz, 93-510
Alvamed
Poznan, 61-828
Instytut Hematologii Ii Transfuzjologii
Warsaw, 02-776
SP Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw, 50-367
Spain4 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, La Coruña, 15006
Hospital Universitario La Paz
Madrid, 28046
Hospital Regional Universitario de Malaga
Málaga, Málaga, 29010
Hospital Universitari Son Espases
Palma de Mallorca, Balearic Islands, 07010
Turkey (Türkiye)4 sites
Acibadem Hastanesi
Adana, 01130
Akdeniz University
Antalya, 07070
Istanbul University
Istanbul, 34098
Ege University
Izmir, 35040
Ukraine4 sites
NChSH Okhmatdyt of MoHU Center of Children Oncohematology and Bone Marrow Transplantation
Kyiv, 1135
Kyiv CCH #9 Dept of Surgery City SPC of Diagnostics & Treatment of Patients with HP
Kyiv, 4112
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
Lviv, 79044
M.V. Sklifosovskyi Poltava RCH Dept of Gematology HSEIU Ukrainian Medical Stomatological Academy
Poltava, 36011
Bulgaria3 sites
UMHAT "Sv. Georgi", EAD
Plovdiv, 4002
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
Sofia, 1527
MHAT 'Sv. Marina', EAD, Clinic of Clinical Hematology
Varna, 9010
Hungary3 sites
Magyar Honvedseg EK
Budapest, 1134
DE OEC Belgyógyászati Int
Debrecen, 4032
PTE ÁOK
Pécs, 7624
Singapore3 sites
National University Hospital
Singapore, 119074
Singapore General Hospital- Parent
Singapore, 169608
KK Women's And Children's Hospital
Singapore, 229899
Taiwan3 sites
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
Tri-Service General Hospital
Taipei, 11490
Australia2 sites
Royal Brisbane Women's Hospital
Herston, Queensland, 4006
The Perth Blood Institute
Nedlands, Western Australia, 6009
Hong Kong2 sites
University of Hong Kong
Hong Kong
Prince of Wales Hospital
Shatin, 00000
Romania2 sites
Spitalul Clinic Judetean de Urgenta Brasov
Brasov, 500365
Institutul Oncologic ClNa.
Cluj-Napoca, 400124
Sweden2 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, S-41345
Karolinska Universitetssjukhuset
Stockholm, 17176
About this study
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
- 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%)
- To further characterize pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BAX 855
- Conditions
- Hemophilia A
- Being tested
- PEGylated Recombinant Factor VIII
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEGylated Recombinant Factor VIIIBiological
Also called BAX855, BAX 855
Pharmacokinetic (PK) evaluation
PEGylated Recombinant Factor VIIIBiological
Also called BAX 855, BAX855
Standard treatment
PEGylated Recombinant Factor VIIIBiological
Also called BAX855, BAX 855
Intensified treatment
| Study group | Role | What they receive |
|---|---|---|
| Pharmacokinetic (PK) evaluation of BAX 855 | Experimental | Participants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens. Receives: Biological: PEGylated Recombinant Factor VIII |
| FVIII trough target 1-3% | Experimental | Standard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3% Receives: Biological: PEGylated Recombinant Factor VIII |
| FVIII trough target 8-12% | Experimental | Intensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12% Receives: Biological: PEGylated Recombinant Factor VIII |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months
Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Measured: Day 183 to Day 364 (6 months)
Secondary outcomes (25)
Total Annualized Bleeding Rate for Second Six Months
Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Measured: Day 183 to Day 364 (6 months)
Annualized Spontaneous Bleeding Rate for Second Six 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.
Measured: Day 183 to Day 364 (6 months)
Annualized Traumatic Bleeding Rate for Second Six 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.
Measured: Day 183 to Day 364 (6 months)
Annualized Joint Bleeding Rate (AJBR) for Second Six 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.
Measured: Day 183 to Day 364 (6 months)
Total Weight-adjusted Consumption of BAX 855
Total weight-adjusted consumption of BAX 855 were reported.
Measured: From start of study treatment up to 12 months (completion or termination)
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions
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.
Measured: 8 hours after study drug administration
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution
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.
Measured: From start of study treatment up to bleed resolution (up to 12 months)
Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution
Infusions of BAX 855 that were required until bleed resolution were reported.
Measured: From start of study treatment up to 12 months (completion or termination)
Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score
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.
Measured: Baseline, Month 12
Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds
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).
Measured: Day 0 through discharge or 14 days post-surgery
Blood Loss Per Participant in Case of 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).
Measured: Day 0 through discharge or 14 days post-surgery
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Measured: 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
Vital signs included systolic and diastolic blood pressure, pulse rate, respiratory rate, body temperature.
Measured: From start of study treatment up to 12 months (completion or termination)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events
Clinical laboratory assessments included clinical chemistry, hematology, lipid panel, genetics, T-cell, B-cell and NK cell (TBNK) and viral serology.
Measured: From start of study treatment up to 12 months (completion or termination)
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
Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein were reported here.
Measured: From start of study treatment up to 12 months (completion or termination)
Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey
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.
Measured: Baseline, Month 12 (completion or termination)
Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf)
Area under the plasma concentration versus time curve from time 0 to infinity of BAX 855 were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855
IR at Cmax of BAX 855 were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Plasma Half-life (T1/2) of BAX 855
T1/2 of BAX 855 in plasma were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Mean Residence Time (MRT) of BAX 855
MRT of BAX 855 were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Maximum Plasma Concentration (Cmax) of BAX 855
Cmax of BAX 855 were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Time to Maximum Concentration of BAX 855 in Plasma (Tmax)
Tmax of BAX 855 were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Total Body Clearance (CL) of BAX 855
Total body clearance of BAX 855 from blood by the kidney were reported.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Volume of Distribution at Steady State (Vss)
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.
Measured: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Incremental Recovery (IR) Over Time
Incremental recovery was calculated by BAX 855 increment (IU/dL) / BAX 855 dose (IU/kg).
Measured: Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2015 (estimated)
- Study start23 Nov 2015
- Primary completion5 Aug 2018
- Study completion5 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02585960
- Sponsor's protocol ID
- 261303
- Other IDs
- 2014-005477-37, 2014
- Acronym
- PROPEL
- Status last verified
- May 2021
- First submitted
- 21 Oct 2015
- Last updated
- 25 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Escuriola-Ettingshausen C, Klamroth R, Escobar M, Stasyshyn O, Tangada S, Engl W, Honauer I, Lee HY, Chowdary P, Windyga J. Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study. Ther Adv Hematol. 2023 Jul 15;14:20406207231178596. doi: 10.1177/20406207231178596. eCollection 2023.
PubMed 37465396Sun SX, Crawford S. Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab. Expert Rev Hematol. 2023 Mar;16(3):205-211. doi: 10.1080/17474086.2023.2162498. Epub 2023 Jan 18.
PubMed 36655343Klamroth R, Windyga J, Radulescu V, Collins PW, Stasyshyn O, Ibrahim HM, Engl W, Tangada SD, Savage W, Ewenstein B. Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study. Blood. 2021 Apr 1;137(13):1818-1827. doi: 10.1182/blood.2020005673.
PubMed 33150384
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02585960
- Acronym / sponsor ID
- PROPEL / 261303
- Conditions
- Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Study start
- 23 Nov 2015 (actual)
- Primary completion
- 5 Aug 2018 (actual)
- Study completion
- 5 Aug 2018 (actual)
- First posted
- 26 Oct 2015 (estimated)
- Results
- Posted 26 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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%)
- To further characterize pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BAX 855
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pharmacokinetic (PK) evaluation of BAX 855 | Experimental | Biological: PEGylated Recombinant Factor VIIIParticipants will first undergo an initial pharmacokinetic (PK) assessment. Following the PK assessment participants will be randomized to one of 2 dosing regimens. |
| FVIII trough target 1-3% | Experimental | Biological: PEGylated Recombinant Factor VIIIStandard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3% |
| FVIII trough target 8-12% | Experimental | Biological: PEGylated Recombinant Factor VIIIIntensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12% |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study:
- 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:
Key exclusion criteria (25 listed)
- Participants transitioning from another BAX 855 study who meet ANY of the following criteria are not eligible for this 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:
- Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
- 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.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEGylated Recombinant Factor VIIIAlso: BAX855, BAX 855Pharmacokinetic (PK) evaluation | Biological | Pharmacokinetic (PK) evaluation of BAX 855 |
| PEGylated Recombinant Factor VIIIAlso: BAX 855, BAX855Standard treatment | Biological | FVIII trough target 1-3% |
| PEGylated Recombinant Factor VIIIAlso: BAX855, BAX 855Intensified treatment | Biological | FVIII trough target 8-12% |
Primary outcome
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)
Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
25 secondary outcomes
Total Annualized Bleeding Rate 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)
Annualized Traumatic Bleeding Rate for Second Six Months
Time frame: Day 183 to Day 364 (6 months)
Annualized Joint Bleeding Rate (AJBR) for Second Six Months
Time frame: Day 183 to Day 364 (6 months)
Total Weight-adjusted Consumption of BAX 855
Time frame: From start of study treatment up to 12 months (completion or termination)
Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions
Time frame: 8 hours after study drug administration
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)
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)
Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score
Time frame: Baseline, Month 12
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
Blood Loss Per Participant in Case of Surgery
Time frame: Day 0 through discharge or 14 days post-surgery
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)
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)
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 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)
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)
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
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
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
Mean Residence Time (MRT) of BAX 855
Time frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Maximum Plasma Concentration (Cmax) of BAX 855
Time frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
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
Total Body Clearance (CL) of BAX 855
Time frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Volume of Distribution at Steady State (Vss)
Time frame: Pre-infusion, 15 - 30 minutes, 3, 8, 24, 48, 72 and 96 hours post-infusion
Incremental Recovery (IR) Over Time
Time frame: Baseline, Month 3, 6, 7.5, 9, 10.5, 12 (Completion or termination)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37465396Escuriola-Ettingshausen C, Klamroth R, Escobar M, Stasyshyn O, Tangada S, Engl W, Honauer I, Lee HY, Chowdary P, Windyga J. Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study. Ther Adv Hematol. 2023 Jul 15;14:20406207231178596. doi: 10.1177/20406207231178596. eCollection 2023.
- Derived from this study: PubMed 36655343Sun SX, Crawford S. Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab. Expert Rev Hematol. 2023 Mar;16(3):205-211. doi: 10.1080/17474086.2023.2162498. Epub 2023 Jan 18.
- Derived from this study: PubMed 33150384Klamroth R, Windyga J, Radulescu V, Collins PW, Stasyshyn O, Ibrahim HM, Engl W, Tangada SD, Savage W, Ewenstein B. Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study. Blood. 2021 Apr 1;137(13):1818-1827. doi: 10.1182/blood.2020005673.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
83 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PEGylated Recombinant Factor VIII in people with Hemophilia A, run by Baxalta now part of Shire at 83 sites in 22 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 83 sites in United States, Italy, United Kingdom, France, Germany and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02585960, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.