| Primary | Number of Participants With Severe and Moderately Severe Hemophilia A (FVIII ≤ 2%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE | Inhibitor testing will be performed in the central laboratory and a non-zero result must be confirmed in the central laboratory as soon as possible, preferably 1 week after inhibitor testing. Confirmed FVIII inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 Bethesda Units (BU)/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL). | Safety Analysis Set All study participants had severe Hemophilia A, less than 1% Factor VIII levels. (ie there were no moderately severe hemophilia A participants (FVIII levels >1% to ≤ 2%) in this study. | Posted | | Number | | participants | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| | | Title | Denominators | Categories |
|---|
| | |
| |
| Secondary | Number of Participants With Severe Hemophilia A (FVIII ≤ 1%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE | Inhibitor testing will be performed in the central laboratory and a non-zero result must be confirmed in the central laboratory as soon as possible, preferably 1 week after inhibitor testing. Confirmed FVIII inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 Bethesda Units (BU)/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL). | | Posted | | Number | | participants | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Number of Exposure Days of Treatment With Advate Prior to First Positive Factor VIII (FVIII) Confirmed Inhibitor Assessment | Confirmed inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 BU/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL). | | Posted | | Median | Inter-Quartile Range | days | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Number of Participants With Low-titer, High-titer, Transient, and All Factor VIII (FVIII) Inhibitors | - High FVIII inhibitor titer (> 5 Bethesda Unit (BU)/mL) - Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL) | | Posted | | Number | | participants | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Number, Type, and Severity of All Bleeds Experienced When Different Prophylactic Dosing Frequencies Are Used (Once or Twice Per Week and Unknown Frequency) | Nominal Dosing Frequency: - 1 time per week - 2 times per week - Unknown dosing frequency (UK) Bleeding Type (BT): - Skin - Muscle and Soft Tissue - Mucosal - Joint - Other - Multiple - Total Bleeding severity: - Minor - Moderate - Severe - Total | | Posted | | Number | | Bleeds | | 50 exposure days to ADVATE | Bleeds | Bleeds | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Number and Type of Surgeries | - Elective surgery is not allowed during period of first 20 exposure days (EDs) - Peripherally inserted central catheter (PICC) | | Posted | | Number | | surgeries | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Correlation of Known Risk Factors to Factor VIII (FVIII) Inhibitor Formation | | Due to the low number of subjects available for evaluation, no statistical tests were performed to assess associations between known risk factors to inhibitor formation. | Posted | | | | | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Total Factor VIII (FVIII) Consumption by Participant | | Due to the low number of subjects available for evaluation, no statistical tests were performed to assess the total FVIII consumption by participant | Posted | | | | | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | FVIII-Specific Antibody Isotype for All Participants at Study Entry and Every 10 Exposure Days (EDs) | | Summary statistics of FVIII-Specific Antibody Isotypes were not performed due to the early termination of the study | Posted | | | | | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Secondary | Number of Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) at Least Possibly Related to ADVATE | Possibly or probably related adverse events | | Posted | | Number | | adverse events | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM): Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose. |
| |
| Post-Hoc | Number of Participants With Factor VIII (FVIII) Inhibitors by Inhibitor Type (Only 'True' Inhibitors) | 'True' positive inhibitor (PI) defined as any FVIII inhibitor assay result ≥0.6 Bethesda Units (BU)/mL confirmed by central lab on 2 consecutive samples, ie ≥2 PI results (including first PI test, in accordance with study protocol) assessed as either: i. High FVIII inhibitor titer (> 5 BU/mL) ii. Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL). In addition, to be classified as 'true' positive low FVIII inhibitors titer (≥0.6 - ≤5.0 BU/mL), one of following criteria must be met: - a) Lower or absent therapeutic response at infusion of standard replacement doses ("clinically relevant") as deemed by the clinician in charge. - b) Any lab result of binding FVIII antibodies (IgM, IgA, IgG, IgG1, IgG2, IgG3, or IgG4) must be positive. Classification based on first positive FVIII inhibitor assessment. Inhibitor test result is: - > 5 BU/mL, then categorized as a high-titer inhibitor - ≥0.6 BU/mL but ≤5 BU/mL, then categorized as a low-titer. | | Posted | | Number | | participants | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | ADVATE - Prophylactic Regimen | Weekly infusions of ADVATE. Study visits (physical examination, lab tests including FVIII inhibitor tests) every week during the first 10 exposure days (EDs), every 5 weeks during the next 10 EDs and every 10 weeks thereafter. |
| |
| Post-Hoc | Number of Inhibitors in Previously Untreated Patients (PUPs) and Minimally Treated Patients (MTPs) - (Only 'True' Inhibitors) | PUPs = no previous FVIII exposure; MTPs ≤4 previous FVIII exposures 'True' positive inhibitor (PI) = any FVIII inhibitor assay result ≥0.6 Bethesda Units (BU)/mL confirmed by central lab on 2 consecutive samples, ie ≥2 PI results (including first PI test, per study protocol) assessed as either: i. High FVIII inhibitor titer (>5 BU/mL) ii. Low FVIII inhibitor titer (≥0.6 - ≤5.0 BU/mL). In addition, to be classified as 'true' positive low FVIII inhibitors titer (≥0.6 - ≤5.0 BU/mL), one of following criteria must be met: - a) Lower or absent therapeutic response at infusion of standard replacement doses ("clinically relevant") as deemed by clinician in charge. - b) Any lab result of binding FVIII antibodies (IgM, IgA, IgG, IgG1, IgG2, IgG3, or IgG4) must be positive. Classification based on first positive FVIII inhibitor assessment. Inhibitor test result is: - > 5 BU/mL, categorized as high-titer inhibitor - ≥0.6 BU/mL but ≤5 BU/mL, categorized as low-titer | | Posted | | Number | | inhibitors | | 50 exposure days to ADVATE | | | | ID | Title | Description |
|---|
| OG000 | PUPs | No previous FVIII exposure | | OG001 | MTPs | ≤4 previous FVIII exposures |
| |