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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003013-18 | EudraCT Number |
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The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.
This is a randomized, open-label, crossover study during which each participant receives a single injection of rFVIIIFc from 2 different vial concentrations (PK assessment). After the PK assessment, participants are provided with rFVIIIFc for either prophylactic or episodic (on-demand) treatment for up to 6 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rFVIIIFc 1000 / 3000 PK Assessment | Experimental | A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
|
| rFVIIIFc 3000 / 1000 PK Assessment | Experimental | A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rFVIIIFc | Biological | Administered as specified in the treatment arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay | Maximum measured concentration of rFVIIIFc. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Half-life (t½) as Measured by aPTT Clotting Assay |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Bioverativ Therapeutics Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Los Angeles | California | United States | |||
| Research Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | rFVIIIFc 1000 / 3000 | Following a minimum 4-day washout, participants received a single injection 50 IU/kg at strength of 1000 IU/vial of rFVIIIFc (on Injection 1 Day 1) with 96 hours of pharmacokinetic (PK) assessments followed by a minimum of a 5-day washout prior to a second single injection of rFVIIIFc 50 IU/kg at strength of 3000 IU/vial (on Injection 2 Day 1) with 96 hours of PK assessments. After completing the PK assessment, all participants began 1 of 3 continued treatment regimens for up to 6 months:
|
| FG001 | rFVIIIFc 3000 / 1000 | Following the minimum 4-day washout, participants received a single injection 50 IU/kg at strength of 3000 IU/vial of rFVIIIFc (on Injection 1 Day 1) with 96 hours of PK assessments followed by a minimum of a 5-day washout prior to a second single injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial (on Injection 2 Day 1) with 96 hours of PK assessments. After completing the PK assessment, all participants began 1 of 3 continued treatment regimens for up to 6 months:
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| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PK Period 1 |
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| Washout Period |
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| PK Period 2 |
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| Treatment Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | rFVIIIFc 1000 / 3000 | Following the minimum 4-day washout, participants received a single injection 50 IU/kg at strength of 1000 IU/vial of rFVIIIFc (on Injection 1 Day 1) with 96 hours of PK assessments followed by a minimum of a 5-day washout prior to a second single injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial (on Injection 2 Day 1) with 96 hours of PK assessments. After completing the PK assessment, all participants began 1 of 3 continued treatment regimens for up to 6 months:
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
|
From screening (for serious adverse events) or first dose of study drug (for adverse events) until end of study (up to approximately 6 months).
Adverse events presented are treatment-emergent (ie, those that occurred or worsened following the first injection of rFVIIIFc).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Total Active | Following the minimum 4-day washout, participants received their first injection of rFVIIIFc (on Injection 1 Day 1) rFVIIIFc 50 IU/kg at a strength of either 1000 or 3000 IU/vial. The second injection of rFVIIIFc 50 IU/kg at a strength of either 1000 or 3000 IU/vial was administered, in a crossover fashion, after a minimum of a 5-day washout (on Injection 2 Day 1). After completing the PK assessment, all participants began 1 of 3 continued treatment regimens for up to 6 months:
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hydrocele | Congenital, familial and genetic disorders | MedDRA 15.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA 15.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bioverativ Study Medical Director | Bioverativ | clinicaltrials@bioverativ.com |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C587014 | factor VIII-Fc fusion protein |
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Time required for the concentration of the drug to reach half of its original value. |
| Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Clearance (CL) as Measured by the aPTT Clotting Assay | The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay | The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.) | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay | The average time at which the number of absorbed molecules reside in the body, after single-dose administration. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Time of Cmax (Tmax) as Measured by aPTT Clotting Assay | Time at which maximum activity (Cmax) is observed. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay | Area under the plasma concentration time-curve from zero to the last measured concentration. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay | First order rate constant associated with the terminal portion of the curve (lambda z) . | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay | Percentage of AUCinf extrapolated from the last data point to infinity. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay | Dose normalized area under the FVIII activity-time curve. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT | The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Cmax as Measured by Two-Stage Chromogenic Clotting Assay | Maximum measured concentration of rFVIIIFc. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| t½ as Measured by Two-Stage Chromogenic Clotting Assay | Time required for the concentration of the drug to reach half of its original value. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| CL as Measured by Two-Stage Chromogenic Clotting Assay | The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Vss as Measured by Two-Stage Chromogenic Clotting Assay | The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.) | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| MRT as Measured by Two-Stage Chromogenic Clotting Assay | The average time at which the number of absorbed molecules reside in the body, after single-dose administration. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Tmax as Measured by Two-Stage Chromogenic Clotting Assay | Time at which maximum activity (Cmax) is observed. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| AUClast as Measured by Two-Stage Chromogenic Clotting Assay | Area under the plasma concentration time-curve from zero to the last measured concentration. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay | First order rate constant associated with the terminal portion of the curve (lambda z). | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| AUCext as Measured by Two-Stage Chromogenic Clotting Assay | Percentage of AUCinf extrapolated from the last data point to infinity. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| DNAUC as Measured by Two-Stage Chromogenic Clotting Assay | Dose normalized area under the FVIII activity-time curve. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Vz as Measured by Two-Stage Chromogenic Clotting Assay | The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
| Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay | An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. An exact 95% confidence interval (CI) for the proportion of subjects with a confirmed inhibitor was calculated using the Clopper-Pearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall. | Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only) |
| Salt Lake City |
| Utah |
| 84101 |
| United States |
| Research Site | Seattle | Washington | United States |
| Research Site | Herston | Australia |
| Research Site | Perth | Australia |
| Research Site | Basingstoke | United Kingdom |
| Research Site | Cambridge | United Kingdom |
| Research Site | London | United Kingdom |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| BG001 | rFVIIIFc 3000 / 1000 | Following the minimum 4-day washout, participants received a single injection 50 IU/kg at strength of 3000 IU/vial of rFVIIIFc (on Injection 1 Day 1) with 96 hours of PK assessments followed by a minimum of a 5-day washout prior to a second single injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial (on Injection 2 Day 1) with 96 hours of PK assessments. After completing the PK assessment, all participants began 1 of 3 continued treatment regimens for up to 6 months:
|
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | rFVIIIFc 3000 IU | a single injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial |
|
|
| Primary | Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay | Maximum measured concentration of rFVIIIFc. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Half-life (t½) as Measured by aPTT Clotting Assay | Time required for the concentration of the drug to reach half of its original value. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Clearance (CL) as Measured by the aPTT Clotting Assay | The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/h/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay | The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.) | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay | The average time at which the number of absorbed molecules reside in the body, after single-dose administration. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Time of Cmax (Tmax) as Measured by aPTT Clotting Assay | Time at which maximum activity (Cmax) is observed. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay | Area under the plasma concentration time-curve from zero to the last measured concentration. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay | First order rate constant associated with the terminal portion of the curve (lambda z) . | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | 1/h | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay | Percentage of AUCinf extrapolated from the last data point to infinity. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | percentage of AUCinf | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay | Dose normalized area under the FVIII activity-time curve. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL per IU/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT | The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU/dL per IU/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Cmax as Measured by Two-Stage Chromogenic Clotting Assay | Maximum measured concentration of rFVIIIFc. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | t½ as Measured by Two-Stage Chromogenic Clotting Assay | Time required for the concentration of the drug to reach half of its original value. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | CL as Measured by Two-Stage Chromogenic Clotting Assay | The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/h/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Vss as Measured by Two-Stage Chromogenic Clotting Assay | The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.) | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | MRT as Measured by Two-Stage Chromogenic Clotting Assay | The average time at which the number of absorbed molecules reside in the body, after single-dose administration. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Tmax as Measured by Two-Stage Chromogenic Clotting Assay | Time at which maximum activity (Cmax) is observed. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | hours | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | AUClast as Measured by Two-Stage Chromogenic Clotting Assay | Area under the plasma concentration time-curve from zero to the last measured concentration. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay | First order rate constant associated with the terminal portion of the curve (lambda z). | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | 1/h | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | AUCext as Measured by Two-Stage Chromogenic Clotting Assay | Percentage of AUCinf extrapolated from the last data point to infinity. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | percentage of AUCinf | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | DNAUC as Measured by Two-Stage Chromogenic Clotting Assay | Dose normalized area under the FVIII activity-time curve. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | IU*h/dL per IU/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Vz as Measured by Two-Stage Chromogenic Clotting Assay | The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay. | Posted | Geometric Mean | 95% Confidence Interval | mL/kg | Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection |
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| Secondary | Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay | An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. An exact 95% confidence interval (CI) for the proportion of subjects with a confirmed inhibitor was calculated using the Clopper-Pearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall. | The Safety Analysis Set included participants who received at least 1 dose of rFVIIIFc. | Posted | Number | 95% Confidence Interval | percentage of participants | Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only) |
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| 2 |
| 19 |
| 12 |
| 19 |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Post procedural cellulitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Vitamin d deficiency | Metabolism and nutrition disorders | MedDRA 15.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
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Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |