Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02585960 | BAX 855 PK-guided Dosing | PHASE3 | COMPLETED | 135 | — | — | Nov 23, 2015 | Aug 5, 2018 | May 25, 2021 | 83 | United States, Australia +20 |
| NCT02615691 | A Study of PEGylated Recombinant Factor VIII (BAX855) in Previously Untreated Young Children With Severe Hemophilia A | PHASE3 | COMPLETED | 120 | — | — | Nov 12, 2015 | Oct 29, 2024 | Jul 28, 2025 | 91 | United States, Austria +21 |
| NCT02210091 | BAX 855 Pediatric Study | PHASE3 | COMPLETED | 75 | — | — | Oct 31, 2014 | Oct 23, 2015 | May 24, 2021 | 39 | United States, Bulgaria +9 |
| NCT01913405 | Phase 3 Efficacy and Safety Study of BAX 855 in Severe Hemophilia A Patients Undergoing Surgical Procedures | PHASE3 | COMPLETED | 30 | — | — | Dec 20, 2013 | Sep 23, 2016 | May 24, 2021 | 22 | United States, Bulgaria +7 |
| NCT01736475 | Study Investigating a PEGylated Recombinant Factor VIII (BAX 855) for Hemophilia A (PROLONG-ATE Study) | PHASE2 | COMPLETED | 159 | — | — | Jan 31, 2013 | Jul 17, 2014 | May 20, 2021 | 72 | United States, Australia +18 |
| NCT01599819 | BAX 855 Dose-Escalation Safety Study | PHASE1 | COMPLETED | 19 | — | — | Sep 30, 2011 | Jul 27, 2012 | May 5, 2021 | 8 | Bulgaria, Germany +2 |
Annualized bleeding rate was determined by dividing the number of bleeds by observation period in years.
Number of participants who developed 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 had not developed an inhibitor and had greater than or equal to (\>=) 100 EDs when the sample for the last valid inhibitor test was drawn.
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.
Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units \[BU\].
GHEA=Sum of 1-3 ratings: Excellent: 7-9 (no category \<2), Good: 5-7 (no category \<1), Fair: 3-4 (no category \<1) 1. Intraoperative and 2. Postoperative (postoperative day 1) hemostatic efficacy assessments: Excellent=3: Blood Loss (BL) ≤ than expected for procedure type in non-hemophilic population (NHP) (≤100%), Good=2: BL ≤50% more than expect. for procedure type in NHP (101-150%), Fair=1: BL \>50% more than expect. for procedure type in NHP (\>150%), None=0: Significant bleeding-requiring rescue therapy (RT) 3. Perioperative hemostatic efficacy assessment (day 14 or discharge, whatever is first): Excellent=3: BL and required blood transfusions (BT) less than or similar (≤100%) to that expected for procedure type in NHP, Good=2: BL ≤50% more (101-150%) and BT less than or similar to that expected for procedure type in NHP, Fair=1: BL \>50% more (\>150%) and BT greater than expected in NHP, None=0: Significant bleeding-requiring RT, BT substantially greater than expected in NHP
Comparisons between prophylactic and on-demand treatment were based on ABR estimates from a negative binomial regression model, taking into account the treatment regimen, target joints and age at screening, and duration of the observation period for efficacy.
| Arm | Type | Description |
|---|---|---|
| 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. |
| FVIII trough target 1-3% | EXPERIMENTAL | Standard treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 1-3% |
| FVIII trough target 8-12% | EXPERIMENTAL | Intensified treatment arm - PK-guided dosing schedule to achieve a Factor VIII (FVIII) trough of 8-12% |
| All Participants | EXPERIMENTAL | Previously Untreated Patients (PUPs) \< 6 years of age with severe hemophilia A (FVIII \< 1%) and \< 3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion were enrolled in a single arm group. Part A (Main Study): Participants age \<3 years - who had not experienced two joint bleeds received on-demand treatment of 10-80 international units per kilogram (IU/kg) intravenously (IV) depending on the severity of the bleeding episode; and - who experienced maximum of two joint bleeds received prophylaxis treatment with dose of 25-80 IU/kg of BAX 855 IV (based on investigator discretion) once weekly for up to 100 EDs. Part B (Immune tolerance induction \[ITI\] Portion): Participants who met the pre-defined Part B treatment criteria entered Part B of the study for ITI. Participants either received prophylaxis treatment of BAX 855 low dose 50 IU/kg IV, three times a week or high dose 100-200 IU/kg IV, daily at discretion of the investigator according to the institution's standard of care. |
| <6 years old | EXPERIMENTAL | - |
| ≥6 to <12 years | EXPERIMENTAL | - |
| BAX855 | EXPERIMENTAL | Pre-operative loading dose: Single loading dose, pre-surgery administered based on each study participant's individual PK results as well as target trough level for type and character of surgery, dental or invasive procedure being performed. In general, major surgery will target an 80-150% FVIII trough level, and minor surgery will target an initial 30-100% FVIII trough level. Intra-operative and post-operative dosing of BAX855 must be based on pre-dosage measurements of FVIII and the type and character of the surgery performed. |
| Prophylaxis | EXPERIMENTAL | - |
| On-demand | EXPERIMENTAL | - |
| Cohort 1 | EXPERIMENTAL | Low dose of ADVATE followed by low dose of BAX 855 |
| Cohort 2 | EXPERIMENTAL | High dose of ADVATE followed by high dose of BAX 855 |
| Name | Type | Description |
|---|---|---|
| PEGylated Recombinant Factor VIII | BIOLOGICAL | Pharmacokinetic (PK) evaluation |
| ITI | BIOLOGICAL | Immune tolerance induction therapy |
| Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method | BIOLOGICAL | Pharmacokinetic (PK) analysis of ADVATE |
| PEGylated Recombinant factor VIII (rFVIII) | BIOLOGICAL | Lyophilized powder and solvent for solution for injection |
INCLUSION CRITERIA: * Participants transitioning from another BAX 855 study who meet ALL of the following criteria are eligible for this study: 1. Participant has completed the end of study visit of a BAX 855 study or is transitioning from the ongoing Baxalta Continuation Study 261302. 2. Part...