A Safety, Tolerability, and Pharmacokinetics Study of a S... | NCT03205163

NCT03205163

ID	Type	Description	Link
242HA101	Other Identifier	Bioverativ, a Sanofi company

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Low Dose Cohort: Advate 25 IU/kg Then BIVV001 25 IU/kg	Experimental	Participants received a single intravenous (IV) dose of Advate 25 international units per kilogram (IU/kg) on Day 1 of Advate treatment period (3 days) followed by a single IV dose of BIVV001 25 IU/kg in BIVV001 treatment period (BTP) (28 days). Advate treatment period (ATP) consisted of a washout of at least 72 hours which was started from the time of Advate dosing.	Biological: Advate (Low Dose) Biological: BIVV001 (Low Dose)
High Dose Cohort: Advate 65 IU/kg Then BIVV001 65 IU/kg	Experimental	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days) followed by a single IV dose of BIVV001 65 IU/kg in BTP (28 days). ATP consisted of a washout of at least 96 hours which was started from the time of Advate dosing.	Biological: Advate (High Dose) Biological: BIVV001 (High Dose)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Advate (Low Dose)	Biological	Participants received a single IV low dose of Advate 25 IU/kg.	Low Dose Cohort: Advate 25 IU/kg Then BIVV001 25 IU/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During Advate Treatment Period	AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the single dose of Advate but before the single dose of BIVV001. Serious AE (SAE) was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.	Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During BIVV001 Treatment Period	AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the study treatment (BIVV001) and within 28 days after BIVV001 administration. SAE was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.	Up to 28 days after BIVV001 administration
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During Advate Treatment Period	Number of Participants with Clinically Significant Abnormalities in Laboratory tests (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.	Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During BIVV001 Treatment Period

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (Low Dose Comparison)	Cmax of Advate and BIVV001 at low dose was assessed and compared based on One-stage activated partial thromboplastin time (aPTT)-based clotting assay.	For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Ability of the participant, or his legally authorized representative (e.g., parent or legal guardian) if applicable in accordance with local regulations, to understand the purpose and risks of the study and provide signed and dated informed consent/assent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
Severe hemophilia A, defined as less than (<) 1 international units per deciliter (IU/dL) (<1 percent [%]) endogenous FVIII at screening as determined by the one-stage clotting assay from the central laboratory. If the initial screening result was greater than or equal to (>=) 1%, then a repeat endogenous FVIII activity level was performed using the one stage clotting assay from the central laboratory. If the repeated result was < 1 IU/dL (<1%), then the participant met this inclusion requirement.
Previous treatment for hemophilia A, defined as at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
Platelet count >=100,000 cells/ microliter (mcL) at screening (test performed by the central laboratory and reviewed prior to the Day 1 Advate dose).
A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to Day 1 Advate dose: cluster of differentiation 4 (CD4) lymphocyte count greater than (>) 200 cells/millimeter (mm)^3; viral load of <400 copies/mL.

Exclusion Criteria:

Medical History:

Any concurrent clinically significant major disease that, in the opinion of the Investigator, made the participant unsuitable for enrollment.
Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening.
Other known coagulation disorder(s) in addition to hemophilia A.
History of hypersensitivity or anaphylaxis associated with any FVIII product.
Known or suspected allergy to mice, hamsters, or any ingredient in Advate.
History of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors not excluded the participant.

Medications and Procedures:

- Current enrollment or participation within 30 days prior to screening in any other investigational study.

Other:

Inability to comply with study requirements as assessed by the Investigator.
Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
University of California Los Angeles Medical Center		Los Angeles	California	90007	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32905674	Derived	Konkle BA, Shapiro AD, Quon DV, Staber JM, Kulkarni R, Ragni MV, Chhabra ES, Poloskey S, Rice K, Katragadda S, Fruebis J, Benson CC. BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A. N Engl J Med. 2020 Sep 10;383(11):1018-1027. doi: 10.1056/NEJMoa2002699.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Low Dose Cohort (LDC): Advate 25 IU/kg Then BIVV001 25 IU/kg	Participants received a single intravenous (IV) dose of Advate 25 International Units per kilogram (IU/kg) on Day 1 of Advate treatment period (ATP) (3 days) followed by a single IV dose of BIVV001 25 IU/kg in BIVV001 treatment period (BTP) (28 days). ATP consisted of a washout of at least 72 hours which was started from the time of Advate dosing.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 4, 2018	Nov 11, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Number of participants with clinically significant abnormalities (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.

FG0007 subjects
FG0019 subjects

Baseline population included all enrolled participants.

Arm/Group Information

ID	Title	Description
BG000	LDC: Advate 25 IU/kg Then BIVV001 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 of ATP (3 days) followed by a single IV dose of BIVV001 25 IU/kg in BTP (28 days). ATP consisted of a washout of at least 72 hours which was started from the time of Advate dosing.
BG001	HDC: Advate 65 IU/kg Then BIVV001 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days) followed by a single IV dose of BIVV001 65 IU/kg in BTP (28 days). ATP consisted of a washout of at least 96 hours which was started from the time of Advate dosing.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00033.0± 13.81 BG00144.0± 11.65 BG00239.2± 13.43

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

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

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During Advate Treatment Period

AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the single dose of Advate but before the single dose of BIVV001. Serious AE (SAE) was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.

Analysis was performed on safety analysis set which included all participants who received at least 1 dose of Advate.

Posted

Count of Participants

Participants

Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 of ATP (3 days).
OG001	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days).

Units	Counts
Participants	OG0007 OG0019

Title

Denominators

Categories

TEAE

Title	Measurements
	OG0002 OG0011

TESAE

Title	Measurements
	OG000

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During BIVV001 Treatment Period

AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the study treatment (BIVV001) and within 28 days after BIVV001 administration. SAE was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.

Analysis was performed on safety analysis set which included all participants who received at least 1 dose of BIVV001.

Posted

Count of Participants

Participants

Up to 28 days after BIVV001 administration

ID	Title	Description
OG000	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts

Primary

Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During Advate Treatment Period

Number of Participants with Clinically Significant Abnormalities in Laboratory tests (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.

Analysis was performed on safety analysis set.

Posted

Count of Participants

Participants

Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 of ATP (3 days).
OG001	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days).

Units	Counts
Participants	OG000

Primary

Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During BIVV001 Treatment Period

Number of participants with clinically significant abnormalities (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.

Analysis was performed on safety analysis set.

Posted

Count of Participants

Participants

Up to 28 days after BIVV001 administration

ID	Title	Description
OG000	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Primary

Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay

Development of an inhibitor was defined as a neutralizing antibody value of greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL) identified and confirmed by a second test on an independent sample, collected within 2 to 4 weeks of the first positive sample, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.

Analysis was performed on safety analysis set.

Posted

Number

percentage of participants

Up to 28 days after BIVV001 administration

ID	Title	Description
OG000	Low Dose Cohort (LDC): Advate 25 IU/kg Then BIVV001 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 of ATP (3 days) followed by a single IV dose of BIVV001 25 IU/kg in BTP (28 days). ATP consisted of a washout of at least 72 hours which was started from the time of Advate dosing.
OG001	High Dose Cohort (HDC): Advate 65 IU/kg Then BIVV001 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days) followed by a single IV dose of BIVV001 65 IU/kg in BTP (28 days). Advate treatment period consisted of a washout of at least 96 hours which was started from the time of Advate dosing.

Secondary

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (Low Dose Comparison)

Cmax of Advate and BIVV001 at low dose was assessed and compared based on One-stage activated partial thromboplastin time (aPTT)-based clotting assay.

Analysis was performed on pharmacokinetic analysis set (PKAS) which included participants who had adequate blood sample collections (following Advate or BIVV001 administration), to assess key PK parameters, as determined by the PK scientist.

Posted

Geometric Mean

95% Confidence Interval

International unit/deciliter (IU/dL)

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants

Secondary

PK: Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (High Dose Comparison)

Cmax of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

IU/dL

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Half-Life (t1/2) for Advate and BIVV001 (Low Dose Comparison)

Half-life is defined as time required for the concentration of the drug to reach half of its original value. t1/2 of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Half-Life for Advate and BIVV001 (High Dose Comparison)

Half-life is defined as time required for the concentration of the drug to reach half of its original value. t1/2 of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Total Body Clearance (CL) for Advate and BIVV001 (Low Dose Comparison)

Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

milliliter/hour/kilogram (mL/hr/kg)

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Total Body Clearance (CL) for Advate and BIVV001 (High Dose Comparison)

Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

mL/hr/kg

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Volume of Distribution at Steady State (Vss) for Advate and BIVV001 (Low Dose Comparison)

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 plasma concentration of a drug. Vss of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

milliliter/kilogram (mL/kg)

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants

Secondary

PK: Volume of Distribution at Steady State (Vss) for Advate and BIVV001 (High Dose Comparison)

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 plasma concentration of a drug. Vss of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

mL/kg

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants

Secondary

PK: Area Under the Concentration Time Curve (AUC) From Time 0 to Infinity (AUCinfinity) for Advate and BIVV001 (Low Dose Comparison)

AUCinfinity of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hour*international unit/deciliter

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinfinity) for Advate and BIVV001 (High Dose Comparison)

AUCinfinity of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hour*international unit/deciliter

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Mean Residence Time (MRT) for Advate and BIVV001 (Low Dose Comparison)

The average time at which the number of absorbed molecules reside in the body, after single-dose administration. MRT of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Mean Residence Time (MRT) for Advate and BIVV001 (High Dose Comparison)

The average time at which the number of absorbed molecules reside in the body, after single-dose administration. MRT of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Incremental Recovery (IR) for Advate and BIVV001 (Low Dose Comparison)

Incremental Recovery is defined as the increase in the circulating FVIII activity level for one unit (IU) of the FVIII product per kilogram body weight. IR of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

IU/dL per IU/kg

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Incremental Recovery (IR) for Advate and BIVV001 (High Dose Comparison)

Incremental Recovery is defined as the increase in the circulating FVIII activity level for one unit (IU) of the FVIII product per kilogram body weight. IR of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

IU/dL per IU/kg

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Time to 1% Above Baseline for FVIII Activity for Advate and BIVV001 (Low Dose Comparison)

Time to 1% activity is the time required from the start of dosing for the FVIII activity to reach 1 IU/dL (1%) above their baseline levels. Time to 1% above baseline for FVIII Activity of Advate and BIVV001 at low dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

ID	Title	Description
OG000	Advate 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 in ATP (3 days).
OG001	BIVV001 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants	OG000

Secondary

PK: Time to 1% Above Baseline for FVIII Activity for Advate and BIVV001 (High Dose Comparison)

Time to 1% activity is the time required from the start of dosing for the FVIII activity to reach 1 IU/dL (1%) above their baseline levels. Time to 1% above baseline for FVIII Activity of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.

Analysis was performed on PKAS.

Posted

Geometric Mean

95% Confidence Interval

hours

For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, 240, 288, and 336 hours

ID	Title	Description
OG000	Advate 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 in ATP (4 days).
OG001	BIVV001 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Advate Dose Level: 25 IU/kg	Participants received a single IV dose of Advate 25 IU/kg on Day 1 of ATP (3 days).	7	1	7	1	7
EG001	Advate Dose Level: 65 IU/kg	Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days).	9	0	9	1	9
EG002	BIVV001 Dose Level: 25 IU/kg	Participants received a single IV dose of BIVV001 25 IU/kg on Day 1 in BTP (28 days).	6	1	6	3	6
EG003	BIVV001 Dose Level: 65 IU/kg	Participants received a single IV dose of BIVV001 65 IU/kg on Day 1 in BTP (28 days).	9	0	9	6	9

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0021 affected6 at risk EG0030 affected9 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG0031 affected9 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0021 affected6 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0021 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Coagulation test abnormal	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Fibrin d dimer increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected9 at risk EG0020 affected6 at risk EG003
Thrombin-antithrombin iii complex increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected9 at risk EG0021 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0020 affected6 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0021 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected9 at risk EG0021 affected6 at risk EG003

ID	Term
D006467	Hemophilia A

Ancestor Terms

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Term
D005169	Factor VIII
C000710888	BIVV001

Units	Counts
Participants	OG0007 OG0019

ID	Term
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011498	Protein Precursors
D001685	Biological Factors