Study of Coagulation Faction VIIa Variant Marzeptacog Alf... | NCT04072237

NCT04072237

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
Study Population	Experimental	MarzAA (Coagulation Factor VIIa variant) 18 µg/kg intravenously (Stage 1) followed by MarzAA 30 µg/kg subcutaneously (SC) (Stage 2), MarzAA 45 µg/kg SC (Stage 3), MarzAA 60 µg/kg SC (Stage 4), MarzAA 2x30 µg/kg SC (Stage 5), MarzAA 90 µg/kg SC (Stage 6), MarzAA 120 µg/kg SC (Stage 7), MarzAA 2×60 µg/kg SC (Stage 8), MarzAA 3x60 µg/kg SC (Stage 9)	Biological: MarzAA (marzeptacog alfa [activated])

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MarzAA (marzeptacog alfa [activated])	Biological	Single intravenous dose and ascending doses of subcutaneous injection of MarzAA (Coagulation Faction VIIa Variant)	Study Population

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last	Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups	Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.
Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose	Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups	Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

Secondary Outcomes

Measure	Description	Time Frame
Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax	Change in Cmax at each stage for each dose group	Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Howard Levy, MD, PhD, MMM	Sponsor GmbH	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Medical Center "Hippocrates - N"		Plovdiv			Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

ID	Title	Description
FG000	Overall Study Population	Coagulation Factor VIIa variant: Single intravenous dose and ascending doses of subcutaneous injection of MarzAA

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

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 25, 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

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Study Population	MarzAA (Marzeptacog Alfa [activated], Coagulation Factor VIIa variant) 18 µg/kg intravenously (Stage 1) followed by MarzAA 30 µg/kg subcutaneously (SC) (Stage 2), MarzAA 45 µg/kg SC (Stage 3), MarzAA 60 µg/kg SC (Stage 4), MarzAA 2x30 µg/kg SC (Stage 5), MarzAA 90 µg/kg SC (Stage 6), MarzAA 120 µg/kg SC (Stage 7), MarzAA 2×60 µg/kg SC (Stage 8), MarzAA 3x60 µg/kg SC (Stage 9)

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG00011
>=65 years	BG000

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000
Male	BG00011

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG0000

Region of Enrollment

Number

participants

Title

Denominators

Categories

Bulgaria

Title	Measurements
	BG0008

Russia

Title	Measurements
	BG000

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

Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last

Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups

Posted

Mean

Standard Deviation

h*ng/mL

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant
OG005	Stage 6 MarzAA 90 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG006	Stage 7 MarzAA 120 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG007	Stage 8 2×60 µg/kg SC Q3H	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours
OG008	Stage 9 3×60 µg/kg SC Q3H	Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours

Units	Counts
Participants	OG00010 OG0018 OG0028 OG003

Title

Denominators

Categories

AUC0-∞

Title	Measurements
	OG0001390.0± 433.99 OG001516.4± 170.01 OG002849.4± 275.00 OG003

Primary

Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose

Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups

Posted

Mean

Standard Deviation

h*kg/mL

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax

Change in Cmax at each stage for each dose group

Posted

Mean

Standard Deviation

ng/mL

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax

Change in Tmax at each stage for each dose group

Posted

Mean

Standard Deviation

hour

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα

Change in T1/2eqα at each stage for each dose group

Posted

Mean

Standard Deviation

hours

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z

Change in T1/2λ-z at each stage for each dose group

Posted

Mean

Standard Deviation

hours

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - CL

Change in CL at each stage for each dose group

Posted

Mean

Standard Deviation

mL/h

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1

Change in Vd1 at each stage for each dose group

Posted

Mean

Standard Deviation

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs

Change in BAabs at each stage for each dose group

Posted

Mean

Standard Deviation

Percentage

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time

Change in Mean Residence Time at each stage for each dose group

Posted

Mean

Standard Deviation

hours

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose

PK analysis by route of administration, dose level/stage of the study based on examination of AUC for each of the dose groups.

Split dose (2*30 µg/kg) vs. (60 µg/kg)

Posted

Mean

Standard Deviation

h*kg/mL

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 4 MarzAA 60μg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG001	Stage 5 MarzAA 2×30μg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Units	Counts
Participants	OG000

Secondary

Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc

PK analysis by route of administration, dose level/stage of the study based on examination of AUC for each of the dose groups.

Split dose (2*30 µg/kg) vs. (60 µg/kg)

Posted

Mean

Standard Deviation

h*ng/mL

Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

ID	Title	Description
OG000	Stage 4 MarzAA 60μg/kg SC	Single subcutaneous injection of MarzAA coagulation factor VIIa variant
OG001	Stage 5 MarzAA 2×30μg/kg SC	Two subcutaneous injections of MarzAA coagulation factor VIIa variant

Units	Counts
Participants	OG000

Secondary

Change in Coagulation Parameters - Prothrombin Time (PT)

Maximum change in PT from pre-dose

Posted

Mean

Standard Deviation

seconds

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg SC	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)

Maximum change in aPTT from pre-dose

Posted

Mean

Standard Deviation

seconds

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg SC	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak

Maximum change in TGT parameter from pre-dose

Posted

Mean

Standard Deviation

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak

Maximum change in TGT parameters from pre-dose

Posted

Mean

Standard Deviation

minutes

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential

Maximum change in TGT parameter from pre-dose

Posted

Mean

Standard Deviation

nM•minutes

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Change in Thrombogenicity Parameter - Fibrinogen

Maximum change in thrombogenicity parameter from pre-dose

Posted

Mean

Standard Deviation

mg/dL

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2

Maximum change in thrombogenicity parameter from pre-dose

Posted

Mean

Standard Deviation

pmol/L

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Thrombogenicity Parameter - Thrombin/Antithrombin

Maximum change in thrombogenicity parameter from pre-dose

Posted

Mean

Standard Deviation

µg/L

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

Secondary

Change in Thrombogenicity Parameter - D-Dimer

Maximum change in thrombogenicity parameter from pre-dose

Posted

Mean

Standard Deviation

mg/L Fibrinogen Equivalent Unit

From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Secondary

Occurrence of an Antibody Response to MarzAA

Occurrence of an antibody response to MarzAA and whether it is inhibitory and cross-reactive to wild-type recombinant coagulation FVII (wt-rFVII) or wt-FVIIa

Posted

Number

participants with an occurrence

From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant

Secondary

Occurrence of Clinical Thrombotic Event

Occurrence of clinical thrombotic event not attributable to another cause

Posted

Number

participants with an occurrence

From the date of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.

ID	Title	Description
OG000	Stage 1 MarzAA 18 µg/kg IV	Single intravenous dose of MarzAA, coagulation factor VIIa variant
OG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA, coagulation factor VIIa variant
OG004	Stage 5 MarzAA 2×30 µg/kg SC

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage 1 MarzAA 18 µg/kg SC	Single intravenous dose of MarzAA	11	11	0	11
EG001	Stage 2 MarzAA 30 µg/kg SC	Single subcutaneous injection of MarzAA	8	8	3	8
EG002	Stage 3 MarzAA 45 µg/kg SC	Single subcutaneous injection of MarzAA	8	8	0	8
EG003	Stage 4 MarzAA 60 µg/kg SC	Single subcutaneous injection of MarzAA	8	8	1	8
EG004	Stage 5 MarzAA 2×30 µg/kg SC	Two subcutaneous injections of MarzAA	8	8	1	8
EG005	Stage 6 MarzAA 90 µg/kg SC	Single subcutaneous injection of MarzAA	8	8	0	8
EG006	Stage 7 MarzAA 120 µg/kg SC	Single subcutaneous injection of MarzAA	8	8	2	8
EG007	Stage 8 MarzAA 2×60 µg/kg SC Q3H	Two subcutaneous injections of MarzAA every 3 hours	8	8	3	8
EG008	Stage 9 MarzAA 3×60 µg/kg SC Q3H	Three subcutaneous injections of MarzAA every 3 hours	8	8	2	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site reaction	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG0031 events1 affected8 at risk EG0040 events0 affected8 at risk EG0050 events0 affected8 at risk EG0062 events2 affected8 at risk EG0074 events3 affected8 at risk EG0082 events2 affected8 at risk
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 affected8 at risk EG0020 events0 affected8 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003

ID	Term
D006467	Hemophilia A
D002836	Hemophilia B

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
D040181	Genetic Diseases, X-Linked

ID	Term
C000656146	marzeptacog alfa (activated)

OG0041025.6± 328.31

OG0051487.9± 429.39

OG0062087.6± 648.85

OG0072108.0± 409.00

OG0083235.5± 735.43

Two single subcutaneous injections of MarzAA, coagulation factor VIIa variant

Two subcutaneous injections of MarzAA, coagulation factor VIIa variant

EG0040 events0 affected8 at risk

EG0050 events0 affected8 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected8 at risk

EG0081 events1 affected8 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected8 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected8 at risk

EG0080 events0 affected8 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected8 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected8 at risk

EG0080 events0 affected8 at risk