| Primary | Serious AEs (SAEs) and Non-serious AEs Occurring After Infusion With BAX 826 | Serious Adverse Events and non-serious Adverse Events the occurred after infusion with BAX 826. | Participants in Cohort 1, 2 and 3 in Period 2 (receiving BAX 826) are included. | Posted | | Number | | Adverse Events | | Up to 6 weeks ± 4 days post infusion with BAX826. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG002 | Cohort 3 - High Dose | After data from Cohort 2 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
| | | Title | Denominators | Categories |
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| Any AE | | | | Any AE with outcome = Death | | |
| |
| Primary | Immediate Tolerability (Vital Signs and Clinical Laboratory Assessments) | Clinically significant results after treatment with investigational product that constitute an AE are counted. Vital signs include body temperature, respiratory rate, pulse rate, and blood pressure. Clinical laboratory results include: Hematology (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (i.e. basophils, eosinophils, lymphocytes, monocytes and neutrophils), international normalized ratio (INR), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count. Clinical Chemistry: sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), creatinine, glucose. Lipid panel: cholesterol, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides | | Posted | | Count of Participants | | Participants | | Screening (Day -30 to -2); Advate Administration (Study Day 1) pre & postdose, and Day 4; Advate washout 96 hours to 4 weeks; BAX826 Administration Day 1 pre & postdose, Post BAX826 Day 4, 8, 14, and 23; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
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| Primary | Immunogenicity: Inhibitory Antibodies to Factor VIII (FVIII) | Inhibition of FVIII activity by antibodies binding to FVIII were measured using the Nijmegen modification of the Bethesda inhibitor assay. | The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result. | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Primary | Immunogenicity: Binding Antibodies to PSA-FVIII (ie BAX 826) | Binding antibodies to PSA FVIII (ie BAX 826) IgG and IgM | The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result. | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose ADVATE | Participants received an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG001 | Cohort 2 - Medium Dose ADVATE | Participants received an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG002 | Cohort 3 - High Dose ADVATE | Participants received an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. |
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| Primary | Immunogenicity: Binding Antibodies to Factor VIII (FVIII) | Binding antibodies to FVIII IgG and IgM | The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result. | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose ADVATE | Participants received an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG001 | Cohort 2 - Medium Dose ADVATE | Participants received an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG002 | Cohort 3 - High Dose ADVATE | Participants received an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. |
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| Primary | Immunogenicity: Anti-polysialic Acid (Anti-PSA) Antibodies | Binding antibodies to PSA (IgG and IgM) | The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result. | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose ADVATE | Participants received an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG001 | Cohort 2 - Medium Dose ADVATE | Participants received an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. | | OG002 | Cohort 3 - High Dose ADVATE | Participants received an infusion of 75±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. |
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| Primary | Immunogenicity: Anti-Chinese Hamster Ovary (Anti-CHO) Antibodies | Binding antibodies to CHO | The immunogenicity analysis was performed on the participants of the safety population (participants who received at least one administration of BAX 826 or ADVATE) who have a predose and at least one postdose result. | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. | | OG001 | Cohort 2 - Medium Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
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| Primary | Immunogenicity: Human Anti-murine Antibodies (HAMA) | Binding antibodies HAMA (IgG) | | Posted | | Count of Participants | | Participants | | Screening visit (Day -30 to -2); Advate Administration (Study Day 1) predose; ADVATE wash out period 96 hours to 4 weeks; BAX826 Administration Day 1 predose, and Post BAX826 Day 8; and study termination visit, week 6 ± 4 days | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. | | OG001 | Cohort 2 - Medium Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. | | OG002 | Cohort 3 - High Dose | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 10 evaluable participants; Cohort 2: 10 evaluable participants; Cohort 3: 10 evaluable participants]. Participants will be recruited to the next dose level only after short-term safety has been reviewed and subject to approval by a Safety Review Committee at the preceding dose level. |
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| Secondary | Pharmacokinetics: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-∞) | Area under the FVIII activity-time curve from zero extrapolated to infinity, calculated by linear-up/log-down trapezoidal method and extrapolated to infinity, calculated as AUC last + C last / lambda z, where Clast is the estimated concentration at the last quantifiable time point | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | IU*h/dL | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Terminal Half-life (t1/2) | Terminal elimination phase half-life, calculated by (ln2)/lambda z, where lambda z is the terminal rate constant, determined by linear regression of the terminal points of the log-linear FVIII activity-time curve. | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | hours | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Mean Residence Time (MRT) | Mean residence time, calculated as (AUMC 0-∞ / AUC 0-∞) - TI / 2, where TI is the time duration of infusion | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | hours | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Total Body Clearance (CL) | Systemic body clearance of drug from plasma, calculated by dose (IU/kg)/AUC0-∞ | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | dL/kg*h | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Incremental Recovery (IR) | Incremental recovery (IR) at Cmax, calculated as IR = (Cmax - Cpreinfusion) / Dose (IU/kg) | In period 1 (ADVATE) the number of participants is 11,15,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (9 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | (IU/dL)/(IU/kg) | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Volume of Distribution at Steady State (Vss) | Volume of distribution at steady state is calculated by MRT*CL MRT=Mean residence time CL=Clearance rate | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | dL/kg | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Maximum Plasma Concentration (Cmax) | Maximum observed FVIII activity, obtained directly from FVIII activity versus time data | In period 1 (ADVATE) the number of participants is 11,15,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (9 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | IU/dL | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Time to Maximum Concentration in Plasma (Tmax) | Time of maximum FVIII activity is obtained directly from FVIII activity versus time data | In period 1 (ADVATE) the number of participants is 11,15,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (9 participants were excluded from the PK analysis for period 2). | Posted | | Median | Full Range | hours | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC0-last) | Area under the FVIII activity-time curve from zero to the last quantifiable FVIII activity, calculated by linear-up/log-down trapezoidal method. | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | IU*h/dL | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 72 Hours (AUC0-72h) | AUC from time zero to exactly 72 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 72 hours is missing, the activity at 72 hours will be interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). | In period 1 (ADVATE) the number of participants is 11,16,12 respectively for Cohorts 1, 2 and 3. In period 2 (BAX 826) the number of participants is 8, 10 and 11 respectively for cohorts 1, 2 and 3 (10 participants were excluded from the PK analysis for period 2). | Posted | | Geometric Mean | Geometric Coefficient of Variation | IU*h/dL | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Pharmacokinetics: Area Under the Concentration-time Curve From 0 to 168 Hours (AUC0-168h) for BAX 826 | AUC from time zero to exactly 168 hours, calculated by linear-up/log-down trapezoidal method. If the sample at 168 hours is missing, the activity at 168 hours was interpolated or extrapolated using the last quantifiable activity and the terminal rate constant (lambda z). This parameter will be calculated for BAX 826 only. | | Posted | | Geometric Mean | Geometric Coefficient of Variation | IU*h/dL | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Comparison of Key Pharmacokinetic Parameters by Cohort | The key pharmacokinetic parameters (Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from 0 to 72 hours (AUC0-72h), Maximum plasma concentration (Cmax), Terminal half-life (t1/2), Mean residence time (MRT) and Total body clearance (CL)) for ADVATE and BAX 826 have been compared. | | Posted | | Number | 95% Confidence Interval | Ratio of Geometric Means (%) | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, and 72 hours for both BAX 826 and ADVATE. BAX 826 will also include post-infusion at 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
|---|
| OG000 | Cohort 1 - Low Dose | Participants were to receive an infusion of 25±3 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. | | OG001 | Cohort 2 - Medium Dose | After data from Cohort 1 have been reviewed and approved by an internal Safety Monitoring Committee, participants were to receive an infusion of 50±5 IU/kg ADVATE followed by a minimum 4-day (96 hours) wash out period including a 3 day PK evaluation. Following the washout period, participants were to receive a single dose of BAX 826, equivalent to the ADVATE dose they had received, followed by a 7-day PK evaluation. |
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| Secondary | Summary of Assessment of Dose Proportionality for BAX 826 | Dose Proportionality for BAX 826 was calculated for the parameters Area under the concentration-time curve from 0 to infinity (AUC0-∞), Area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-last) and Maximum plasma concentration (Cmax). | The PK analysis set consists of all subjects that have received at least 1 administration of ADVATE or BAX 826 and are evaluable for PK for one or both treatments. | Posted | | Number | 95% Confidence Interval | Doubling dose increase | | Pre-infusion within 30 minutes; and post-infusion at 15 and 30 minutes, and 1, 3, 6, 9, 12, 24, 32, 48, 56, 72, 96, 120, 144, and 168 hours. | | | | ID | Title | Description |
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| OG000 | Pharmacokinetic Analysis Data Set | The PK analysis set includes all participants that underwent pharmacokinetic assessments. |
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