Hemophilia APhase 1NCT02716194
BAX 826 Dose-Escalation Safety Study
A Phase 1 study testing BAX 826 and Octocog alfa in people with Hemophilia A, run by Baxalta now part of Shire at 28 sites in 9 countries.
Trial summary
1. To assess tolerability and safety of BAX 826 after a single infusion in previously treated patients (PTPs) with severe hemophilia A 2. To determine the pharmacokinetic (PK) parameters of BAX 826 compared to ADVATE 3. To evaluate immunogenicity of polysialic acid linked to Factor VIII (FVIII) Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- BAX 826 and Octocog alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 28 sitesin 9 countries
- Study dates
- 3 Mar 2016to 17 Jan 2017
- Phase
- Phase 1
- 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 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previously treated male participants aged 18 to 65 years (inclusive) at the time of screening
- Diagnosis of severe hemophilia A (Factor VIII level <1%)
- Previously treated with FVIII concentrates for ≥150 documented Exposure Days (EDs)
- Karnofsky performance score of ≥60
- Human immunodeficiency virus negative (HIV-); or HIV+ with stable disease
- Hepatitis C virus negative (HCV-); or HCV+ with chronic stable hepatitis as assessed by the investigator
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- Able to understand and have provided written informed consent including signature on an informed consent form (ICF) approved by an ethics committee (EC)
- Have provided written authorization for use and disclosure of protected health information
- Agree to abide by the study schedule and to return for the required assessments
- Willing and able to comply with the requirements of the protocol
Who cannot join
- Detectable FVIII inhibitor at screening, with a titer ≥0.6 Bethesda Unit (BU)
- Documented history of FVIII inhibitors with a titer ≥0.4 BU at any time prior to screening
- Known clinical hypersensitivity towards mouse or hamster proteins or to polysialic acid (PSA)
- Scheduled elective surgery during study participation
- Severe chronic hepatic dysfunction
- Severe renal impairment
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- Currently receiving, or has recently received (less than 3 months prior to study participation), or is scheduled to receive during the course of the study, other PSA-ylated drugs
- Have received another investigational drug within 30 days prior to study entry and/or is scheduled to receive additional investigational drug during the course of the study in the context of another investigational drug study
- Diagnosis of an inherited or acquired hemostatic defect other than hemophilia A
- Currently receiving, or scheduled to receive during the course of the study, an immune-modulating drug other than antiretroviral chemotherapy
- Has a clinically significant medical, psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect the safety or compliance of the participant during the study
- Is a family member or employee of the investigator
Trial locations and contacts
28 sites in 9 countries.
28 sites in 9 countries
Spain6 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, La Coruña, 15006
Hospital General Universitario de Alicante
Alicante, 03010
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Regional Universitario de Malaga
Málaga, 29010
Hospital Universitario Son Espases
Palma de Mallorca, 07120
United Kingdom6 sites
University Hospital of Wales
Cardiff, West Glamorgan, CF14 4XW
Royal London Hospital
London, Greater London, E1 1BB
Royal Free Hospital
London, Greater London, NW3 2QG
St Thomas' Hospital Centre for Haemostasis & Thrombosis
London, Greater London, SE1 7EH
Manchester Royal Infirmary
Manchester, Greater Manchester, M13 9WL
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LJ
Germany5 sites
Vivantes Klinikum im Friedrichshain - Landsberger Allee
Berlin, 10249
Werlhof-Institut
Hanover, Lower Saxony, 30159
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Universitaetsklinikum des Saarlandes
Homburg, 66421
Universitaetsklinikum Gießen
Marburg, 35043
Italy3 sites
Presidio Ospedaliero di Castelfranco Veneto
Castelfranco Veneto, Treviso, 31033
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Policlinico Umberto I di Roma-Università di Roma La Sapienza
Roma, 00144
Russia3 sites
FSBI "Kirov SR Institute of Hematology and Blood Transfusion FMBA"
Kirov, 610027
FSBI "Hematological Research Center" MoH of RF
Moscow, 125167
SBEI HPE "Samara State Medical University" of the MoH of the RF
Samara, 443099
Netherlands2 sites
Radboud University Nijmegen Medical Centre
Nijmegen, 6525 GA
Erasmus Medisch Centrum
Rotterdam, 3015 AA
Hungary1 site
Semmelweis Egyetem AOK I.sz. Belgyogyaszati Klinika
Budapest, 1083
About this study
Official title: A Phase 1, Prospective, Open Label, Two Period, Fixed Sequence, Dose-Escalation Study of the PK and Safety of BAX 826 (PSA-rFVIII) in Previously Treated Patients With Severe (FVIII <1%) Hemophilia A
- To assess tolerability and safety of BAX 826 after a single infusion in previously treated patients (PTPs) with severe hemophilia A
- To determine the pharmacokinetic (PK) parameters of BAX 826 compared to ADVATE
- To evaluate immunogenicity of polysialic acid linked to Factor VIII (FVIII)
- Conditions
- Hemophilia A
- Being tested
- BAX 826, Octocog alfa
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAX 826Biological
Also called BAX826
Octocog alfaBiological
Also called ADVATE (Antihemophilic Factor [Recombinant]), ADVATE
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Low dose | Experimental | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. Receives: Biological: BAX 826; Biological: Octocog alfa |
| Cohort 2 - Medium dose | Experimental | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. Receives: Biological: BAX 826; Biological: Octocog alfa |
| Cohort 3 - High dose | Experimental | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. Receives: Biological: BAX 826; Biological: Octocog alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826
Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.
Measured: Up to 6 weeks ± 4 days post infusion with BAX826.
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments)
Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides
Measured: Screening (Day -30 to -2); Advate Administration (Study Day 1) pre & postdose, and Day 4; Advate washout 96 hours to 4 weeks; BAX826 Administration Day 1 pre & postdose, Post BAX826 Day 4, 8, 14, and 23; and study termination visit, week 6 ± 4 days
Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII)
Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay.
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826)
Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Immunogenicity: Binding Antibodies to Factor VIII (FVIII)
Binding antibodies to FVIII IgG and IgM
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies
Binding antibodies to PSA (IgG and IgM)
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies
Binding antibodies to CHO
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Immunogenicity: Human Anti-murine Antibodies (HAMA)
Binding antibodies HAMA (IgG)
Measured: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Secondary outcomes (13)
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞)
Area under the FVIII activity-time curve from zero extrapolated to infinity, calculated by linear-up/log-down trapezoidal method and extrapolated to infinity, calculated as AUC last + C last / lambda z, where Clast is the estimated concentration at the last quantifiable time point
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Terminal Half-life (t1/2)
Terminal elimination phase half-life, calculated by (ln2)/lambda z, where lambda z is the terminal rate constant, determined by linear regression of the terminal points of the log-linear FVIII activity-time curve.
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Mean Residence Time (MRT)
Mean residence time, calculated as (AUMC 0-∞ / AUC 0-∞) - TI / 2, where TI is the time duration of infusion
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Total Body Clearance (CL)
Systemic body clearance of drug from plasma, calculated by dose (IU/kg)/AUC0-∞
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Incremental Recovery (IR)
Incremental recovery (IR) at Cmax, calculated as IR = (Cmax - Cpreinfusion) / Dose (IU/kg)
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Volume of distribution at steady state is calculated by MRT*CL MRT=Mean residence time CL=Clearance rate
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Maximum observed FVIII activity, obtained directly from FVIII activity versus time data
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax)
Time of maximum FVIII activity is obtained directly from FVIII activity versus time data
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last)
Area under the FVIII activity-time curve from zero to the last quantifiable FVIII activity, calculated by linear-up/log-down trapezoidal method.
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h)
AUC from time zero to exactly 72 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 72 hours is missing, the activity at 72 hours will be interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z).
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826
AUC from time zero to exactly 168 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 168 hours is missing, the activity at 168 hours was interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). This parameter will be calculated for BAX 826 only.
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
Comparison of Key Pharmacokinetic Parameters by Cohort
The key pharmacokinetic parameters (Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from 0 to 72 hours (AUC0-72h), Maximum plasma concentration (Cmax), Terminal half-life (t1/2), Mean residence time (MRT) and Total body clearance (CL)) for ADVATE and BAX 826 have been compared.
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Summary of Assessment of Dose Proportionality for BAX 826
Dose Proportionality for BAX 826 was calculated for the parameters Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-last) and Maximum plasma concentration (Cmax).
Measured: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2016 (estimated)
- Study start3 Mar 2016
- Primary completion17 Jan 2017
- Study completion17 Jan 2017
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 (1)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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02716194
- Sponsor's protocol ID
- 291501
- Other IDs
- 2015-004079-60, 2015
- Status last verified
- May 2021
- First submitted
- 17 Mar 2016
- Last updated
- 25 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Tiede A, Allen G, Bauer A, Chowdary P, Collins P, Goldstein B, Jiang HJ, Kӧck K, Takacs I, Timofeeva M, Wolfsegger M, Srivastava S. SHP656, a polysialylated recombinant factor VIII (PSA-rFVIII): First-in-human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A. Haemophilia. 2020 Jan;26(1):47-55. doi: 10.1111/hae.13878. Epub 2019 Nov 28.
PubMed 31778283
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
- A Phase 1, Prospective, Open Label, Two Period, Fixed Sequence, Dose-Escalation Study of the PK and Safety of BAX 826 (PSA-rFVIII) in Previously Treated Patients With Severe (FVIII <1%) Hemophilia A
- ClinicalTrials.gov ID
- NCT02716194
- Acronym / sponsor ID
- 291501
- Conditions
- Hemophilia A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 3 Mar 2016 (actual)
- Primary completion
- 17 Jan 2017 (actual)
- Study completion
- 17 Jan 2017 (actual)
- First posted
- 23 Mar 2016 (estimated)
- Results
- Posted 20 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To assess tolerability and safety of BAX 826 after a single infusion in previously treated patients (PTPs) with severe hemophilia A
- To determine the pharmacokinetic (PK) parameters of BAX 826 compared to ADVATE
- To evaluate immunogenicity of polysialic acid linked to Factor VIII (FVIII)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Low dose | Experimental | Biological: BAX 826, Biological: Octocog alfaThe study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
| Cohort 2 - Medium dose | Experimental | Biological: BAX 826, Biological: Octocog alfaThe study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
| Cohort 3 - High dose | Experimental | Biological: BAX 826, Biological: Octocog alfaThe study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Previously treated male participants aged 18 to 65 years (inclusive) at the time of screening
- Diagnosis of severe hemophilia A (Factor VIII level <1%)
- Previously treated with FVIII concentrates for ≥150 documented Exposure Days (EDs)
- Karnofsky performance score of ≥60
- Human immunodeficiency virus negative (HIV-); or HIV+ with stable disease
Key exclusion criteria (12 listed)
- Detectable FVIII inhibitor at screening, with a titer ≥0.6 Bethesda Unit (BU)
- Documented history of FVIII inhibitors with a titer ≥0.4 BU at any time prior to screening
- Known clinical hypersensitivity towards mouse or hamster proteins or to polysialic acid (PSA)
- Scheduled elective surgery during study participation
- Severe chronic hepatic dysfunction
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 |
|---|---|---|
| BAX 826Also: BAX826 | Biological | Cohort 1 - Low dose, Cohort 2 - Medium dose, Cohort 3 - High dose |
| Octocog alfaAlso: ADVATE (Antihemophilic Factor [Recombinant]), ADVATE | Biological | Cohort 1 - Low dose, Cohort 2 - Medium dose, Cohort 3 - High dose |
Primary outcome
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826
Time frame: Up to 6 weeks ± 4 days post infusion with BAX826.
Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826.
Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments)
Time frame: Screening (Day -30 to -2); Advate Administration (Study Day 1) pre & postdose, and Day 4; Advate washout 96 hours to 4 weeks; BAX826 Administration Day 1 pre & postdose, Post BAX826 Day 4, 8, 14, and 23; and study termination visit, week 6 ± 4 days
Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides
Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII)
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay.
Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826)
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM
Immunogenicity: Binding Antibodies to Factor VIII (FVIII)
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Binding antibodies to FVIII IgG and IgM
Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Binding antibodies to PSA (IgG and IgM)
Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Binding antibodies to CHO
Immunogenicity: Human Anti-murine Antibodies (HAMA)
Time frame: Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days
Binding antibodies HAMA (IgG)
13 secondary outcomes
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Terminal Half-life (t1/2)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Mean Residence Time (MRT)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Total Body Clearance (CL)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Incremental Recovery (IR)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h)
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
Comparison of Key Pharmacokinetic Parameters by Cohort
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours.
Summary of Assessment of Dose Proportionality for BAX 826
Time frame: Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours.
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 31778283Tiede A, Allen G, Bauer A, Chowdary P, Collins P, Goldstein B, Jiang HJ, Kӧck K, Takacs I, Timofeeva M, Wolfsegger M, Srivastava S. SHP656, a polysialylated recombinant factor VIII (PSA-rFVIII): First-in-human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A. Haemophilia. 2020 Jan;26(1):47-55. doi: 10.1111/hae.13878. Epub 2019 Nov 28.
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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
28 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAX 826 and Octocog alfa in people with Hemophilia A, run by Baxalta now part of Shire at 28 sites in 9 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 10 inclusion and 12 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 28 sites in Spain, United Kingdom, Germany, Italy, Russia and 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 Sep 2018). 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?
Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 (time frame: Up to 6 weeks ± 4 days post infusion with BAX826.). The study lists 8 primary outcomes in all. 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 NCT02716194, which also lists 1 linked publication.
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.