Phase 3
N=138
Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study)
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT01736475 ↗Enrolled (actual)
138
Serious AEs
3.7%
Results posted
Sep 2016
Primary outcome: Primary: Annualized Bleeding Rate (ABR) — 4.3; 43.4 Bleeds per year — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method (Biological); PEGylated Recombinant Factor VIII (Biological)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Male
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jul 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Bleeding Rate (ABR) |
4.3; 43.4 | <0.0001 sig |
| SECONDARY Rate of Success of BAX 855 for Treatment of Bleeding Episodes |
0.96 | — |
| SECONDARY Average Number of BAX 855 Infusions Needed for the Treatment of Bleeding Episodes |
1.37; 1.21 | — |
| SECONDARY Number of Participants With ≤1, 2, 3, 4, 5, 6, or >6 Month Time Intervals Between Bleeding Episodes or no Bleeding Episodes |
45; 0; 5; 0; 20; 0 | — |
| SECONDARY Weight-adjusted Consumption of BAX 855 - Per Prophylactic Infusion and Pharmacokinetic (PK) Infusion |
44.51; 45.48 | — |
| SECONDARY Weight-adjusted Consumption of BAX 855 - Per Treatment of Bleeding Episode (BE) and Per BE for Maintenance of Hemostasis |
37.44; 39.29 | — |
| SECONDARY Percentage of Participants With Adverse Events |
0.7; 2.9; 40.1; 3.6; 19.0; 1.5 | — |
| SECONDARY Immunogenicity - Number of Participants With Positive Inhibitory Antibodies to FVIII, Binding Antibodies to FVIII, PEG-VIII, PEG and Anti-CHO Antibodies at Study Completion/Termination |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Patient Reported Outcomes: Haemo-SYM Questionnaire, Change in Score From Baseline to End of Study |
-4.17; -4.24; -1.22; -0.17 | — |
| SECONDARY Patient Reported Outcomes - Short Form (SF)-36, Change From Baseline to End of Study |
0.49; -2.46; 1.31; -3.67; 2.08; 0.60 | — |
| SECONDARY Pharmacokinetics (Pk) - Plasma Half-life (One-stage Clotting Assay) |
10.40; 14.30; 16.02 | — |
| SECONDARY Pharmacokinetics (Pk) - Mean Residence Time (One-stage Clotting Assay) |
12.86; 19.56; 20.65 | — |
| SECONDARY Pharmacokinetics (Pk) - Total Body Clearance (One-stage Clotting Assay) |
0.04551; 0.02760; 0.02474 | — |
| SECONDARY Pharmacokinetics (Pk) - Incremental Recovery Over Time (One-stage Clotting Assay) |
2.372; 2.493; 2.297 | — |
| SECONDARY Pharmacokinetics (Pk) - Area Under the Concentration Versus Time Curve From 0 to Infinity (AUC0-∞) (One-stage Clotting Assay) |
1168.0; 2073.3; 2008.7 | — |
| SECONDARY Pharmacokinetics (Pk) - Apparent Volume of Distribution at Steady State (Vss) (One-stage Clotting Assay) |
0.5487; 0.4715; 0.4970 | — |
| SECONDARY Pharmacokinetics (Pk) - Maximum Plasma Concentration (Cmax) (One-stage Clotting Assay) |
108.45; 113.68; 103.34 | — |
| SECONDARY Pharmacokinetics (Pk) -Time to Maximum Concentration in Plasma (Tmax) (One-stage Clotting Assay) |
0.296; 0.397; 0.467 | — |
| SECONDARY Change in Vital Signs From Screening - Temperature |
0.00; 0.00; 0.00; 0.00; -0.10; 0.00 | — |
| SECONDARY Change in Vital Signs From Screening - Pulse Rate |
3.0; 2.0; 2.0; 2.0; 3.0; 4.0 | — |
| SECONDARY Change in Vital Signs From Screening - Respiratory Rate |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Changes in Vital Signs From Screening - Blood Pressure |
0.0; -2.0; -0.5; -1.0; 0.0; 3.5 | — |
| SECONDARY Changes in Clinical Chemistry Laboratory Assessments From Screening - Albumin and Protein |
-1.0; -1.0; -1.0; -1.0; -1.0; -1.0 | — |
| SECONDARY Changes in Clinical Chemistry Laboratory Assessments From Screening - Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase |
-1.0; -5.0; -4.0; -4.5; -2.0; -5.0 | — |
| SECONDARY Changes in Clinical Chemistry Laboratory Assessments From Screening - Bicarbonate, Chloride, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN) |
0.10; 1.10; 0.40; 0.10; 0.60; 0.60 | — |
| SECONDARY Changes in Clinical Chemistry Laboratory Assessments From Screening - Creatinine, and Bilirubin |
0.0; 1.0; 0.0; 0.5; 0.0; 3.0 | — |
| SECONDARY Changes in Hematology Laboratory Assessments From Screening - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes |
0.000; 0.000; 0.000; 0.005; 0.000; 0.000 | — |
| SECONDARY Changes in Hematology Laboratory Assessments From Screening - Hematocrit |
-0.010; 0.000; -0.010; -0.010; 0.000; 0.000 | — |
| SECONDARY Changes in Hematology Laboratory Assessments From Screening - Hemoglobin |
-1.0; 3.0; -1.0; 0.0; 1.0; 3.5 | — |
| SECONDARY Changes in Hematology Laboratory Assessments From Screening - Erythrocytes |
-0.10; 0.10; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Changes in Lipid Panel Assessments From Screening - Cholesterol; High Density Lipoprotein (HDL); Low Density Lipoprotein (LDL); Triglycerides; and Very Low Density Lipoprotein (VLDL) |
-0.130; -0.100; -0.050; -0.190; -0.070; 0.040 | — |
Summary
To assess efficacy and safety, including immunogenicity of BAX 855 administered as prophylaxis and as on-demand therapy in adult and adolescent (12-65 years) previously treated patients (PTPs) with severe hemophilia A To determine the pharmacokinetic (PK) parameters of BAX 855.
Eligibility Criteria
Main Inclusion Criteria:
- Participant and/or legal representative has/have voluntarily provided signed informed consent
- Participant is 12 to 65 years old at the time of screening
- Participant is male with severe hemophilia A (Factor VIII (FVIII) clotting activity < 1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity <1%
- Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥150 documented exposure days (EDs)
- Participant is currently receiving prophylaxis or on-demand therapy with FVIII
- Participant is willing and able to comply with the requirements of the protocol
Main Exclusion Criteria:
- Participant has detectable FVIII inhibitory antibodies (≥ 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
- Participant has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) 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).
Data sourced from ClinicalTrials.gov (NCT01736475). 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.