Phase 1
Completed N=40
BAX 826 Dose-Escalation Safety Study
Source: ClinicalTrials.gov NCT02716194 ↗Enrolled (actual)
40
Serious AEs
0.0%
Results posted
Sep 2018
Primary outcomePrimary: Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 — 20; 12; 15; 0 Adverse Events
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)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 |
20; 12; 15; 0; 0; 0 | — |
| PRIMARY Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII) |
0; 0; 0 | — |
| PRIMARY Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) |
1; 0; 0; 1; 0; 1 | — |
| PRIMARY Immunogenicity: Binding Antibodies to Factor VIII (FVIII) |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies |
0; 0; 0 | — |
| PRIMARY Immunogenicity: Human Anti-murine Antibodies (HAMA) |
0; 0; 0 | — |
| SECONDARY Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) |
901.3; 1771; 2496; 1127; 2363; 2578 | — |
| SECONDARY Pharmacokinetics: Terminal Half-life (t1/2) |
10.57; 11.30; 9.948; 16.18; 16.90; 16.22 | — |
| SECONDARY Pharmacokinetics: Mean Residence Time (MRT) |
15.55; 16.30; 14.00; 26.96; 28.90; 24.33 | — |
| SECONDARY Pharmacokinetics: Total Body Clearance (CL) |
0.02803; 0.02831; 0.02989; 0.02213; 0.02161; 0.02950 | — |
| SECONDARY Pharmacokinetics: Incremental Recovery (IR) |
2.506; 2.594; 3.059; 1.544; 1.560; 1.641 | — |
| SECONDARY Pharmacokinetics: Volume of Distribution at Steady State (Vss) |
0.4359; 0.4615; 0.4183; 0.5967; 0.6246; 0.7176 | — |
| SECONDARY Pharmacokinetics: Maximum Plasma Concentration (Cmax) |
63.32; 130.06; 228.24; 38.53; 79.65; 124.78 | — |
| SECONDARY Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) |
0.3000; 0.3330; 0.3170; 0.3000; 0.5165; 0.5500 | — |
| SECONDARY Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) |
861.8; 1712; 2445; 1078; 2296; 2528 | — |
| SECONDARY Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) |
885.9; 1736; 2463; 1041; 2168; 2421 | — |
| SECONDARY Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826 |
1124; 2358; 2572; 1231; 2739; 3783 | — |
| SECONDARY Comparison of Key Pharmacokinetic Parameters by Cohort |
116.20; 122.53; 100.79; 141.10; 155.57; 138.99 | — |
| SECONDARY Summary of Assessment of Dose Proportionality for BAX 826 |
1.668; 1.979; 1.696; 2.014; 2.058; 2.055 | — |
Eligibility Criteria
Inclusion Criteria
- 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
- 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
Exclusion Criteria
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT02716194). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.