Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PEGylated Recombinant Factor VIII · 6 trials · 1 indication
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...
PEGylated Recombinant Factor VIII is used for the treatment of Hemophilia A. It is an investigational therapy being developed by Takeda Pharmaceutical Company Limited (TAK) and is currently in Phase 3 clinical development. The drug is a PEGylated form of recombinant factor VIII designed to replace the missing clotting factor in patients with Hemophilia A.
PEGylated Recombinant Factor VIII works by replacing the deficient clotting factor VIII in patients with Hemophilia A. The PEGylation process attaches polyethylene glycol molecules to the recombinant factor VIII protein, which may extend its half-life in the body. This allows the drug to maintain effective clotting activity for a longer duration compared to non-PEGylated factor VIII products.
PEGylated Recombinant Factor VIII is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker symbol TAK. The drug is currently in Phase 3 clinical development for the treatment of Hemophilia A. Takeda is conducting multiple clinical trials to evaluate the safety and efficacy of this investigational therapy.
PEGylated Recombinant Factor VIII is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. The Phase 3 program includes studies such as NCT02585960 and NCT02615691, which are evaluating the drug in patients with Hemophilia A, including previously untreated young children with severe disease.
PEGylated Recombinant Factor VIII has been studied in six clinical trials, all of which are completed. Key trials include NCT01599819, a Phase 1 dose-escalation safety study; NCT01736475, a Phase 2 study in the PROLONG-ATE program; NCT02585960, a Phase 3 PK-guided dosing study; and NCT02615691, a Phase 3 study in previously untreated young children with severe Hemophilia A.
Yes, PEGylated Recombinant Factor VIII is also known as BAX 855. The clinical trials for this drug, including NCT01599819, NCT01736475, NCT02585960, and NCT02615691, refer to it as BAX 855. It is an investigational PEGylated recombinant factor VIII product being developed by Takeda for the treatment of Hemophilia A.