Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B

• Sponsor: Catalyst Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03407651
• Collaborator: (none)
• Enrollment: 11
• Locations: 9
• Arms: 3
• Actual Duration (Months): 15.8
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 2, multi-center, open-label study designed to evaluate the PK, bioavailability, PD, efficacy and safety of a daily subcutaneous [SC] treatment regimen with MarzAA for bleeding prophylaxis in 12 adult subjects with hemophilia A or B with an inhibitor and history of frequent spontaneous bleeding episodes.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A With Inhibitor; Hemophilia B With Inhibitor	Biological: Coagulation Factor VIIa variant	Phase 2

Detailed Description

Multi-center, open-label Phase 2 study to evaluate the PK, bioavailability, PD, efficacy and safety of a daily SC treatment regimen with MarzAA for bleeding prophylaxis in adult subjects with hemophilia A or B with an inhibitor. The study will enroll and dose, both intravenously and subcutaneously, a total of 12 adult male subjects with severe congenital hemophilia A or B with an inhibitor, and history of frequent bleeding episodes during the 6 months prior to enrollment, as per the individual's bleeding and treatment records.

Once a subject is enrolled into the trial, the study will be conducted in three parts (occurring consecutively):

Part 1a (24 hours): Single IV administration of MarzAA; Part 1b (48 hours): Single SC administration of MarzAA; Part 2: Daily SC administration. Dose escalation in Part 2 will occur if breakthrough bleeding occurs. Subjects are treated for 50 days at the final dose level required.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of a Daily Subcutaneous Treatment Regimen With Marzeptacog Alfa (Activated) for Bleeding Prophylaxis in Adult Subjects With Hemophilia A and B Subjects With an Inhibitor
• Actual Study Start Date: Dec 18, 2017
• Actual Primary Completion Date: Mar 15, 2019
• Actual Study Completion Date: Apr 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1a Coagulation Factor VIIa variant, 18 µg/kg by intravenous route	Biological: Coagulation Factor VIIa variant; Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.
Experimental: Part 1b Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route	Biological: Coagulation Factor VIIa variant; Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.
Experimental: Part 2 Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route	Biological: Coagulation Factor VIIa variant; Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.

Outcome Measures

Primary Outcome Measures

1. Bleeding Episode Prevention Success [Day 1 of final MarzAA dose level - Day 50]

   Annualized bleed rate (ABR; spontaneous and total) during Part 2 when on final MarzAA dose level versus recorded historical ABR. The analysis of the primary endpoint (annualized bleeding rate ABR for spontaneous and traumatic bleeds) of the final dose of MarzAA each subject was treated was based on the 1-sample test compared to a predefined rate assumed for the on-demand therapy. The latter was assumed to be 12 (or 1 bleed per month), which was the minimum ABR for each subject according to inclusion criterion 2 (defined as the H0), with no maximum value. A higher score indicated a worse outcome. ABR is on a scale of 0 to 365, with a lower score reflective of a lower number of bleeding events in a year.

Secondary Outcome Measures

1. Occurrence of Breakthrough Bleeding [From Day 5 of dose level until occurrence of event]

   Occurrence of breakthrough bleeds requiring escalation to higher dose level

2. Occurrence of Clinical Thrombotic Event [From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50]

   Occurrence of clinical thrombotic event not attributable to another cause

3. Coagulation Assessment - Prothrombin Time [From date of pre-dose to 24 hours (Part 1a), pre-dose to 48 hours (Part 1b), and pre-dose to Day 50 (Part 2)]

   Change in coagulation parameter (prothrombin time [PT]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.

4. Coagulation Assessment - Activated Partial Thromboplastin Time [From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2)]

   Change in coagulation parameter (activated partial thromboplastin time [aPTT]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.

5. Coagulation Assessment - Fibrinogen [From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2).]

   Change in coagulation parameter (fibrinogen) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.

6. Number of Events of Antibody Formation [From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50]

   Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII) or Factor VII activated (FVIIa)

7. Number of Events of an Antibody Response [From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50.]

   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.

8. Thrombogenicity Assessment [From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.]

   Number of participants with clinically significant levels of thrombogenicity markers (D-dimer, Prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex [TAT]), based on standard laboratory tests and clinical examination with a specific search for any signs of thrombosis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Severe congenital hemophilia A or B with an inhibitor.

• History of frequent spontaneous bleeding episodes.

• Male, age 18 or older.

• Affirmation of informed consent with signature confirmation before any trial-related activities.

Exclusion Criteria:

• Receiving prophylaxis treatment.

• Previous participation in a clinical trial evaluating a modified rFVIIa agent.

• Known positive antibody to FVII or FVIIa detected by central laboratory at screening.

• Have a coagulation disorder other than hemophilia A or B.

• Significant contraindication to participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology Center after Prof. R. Yeolyan	Yerevan		Armenia
2	JSC "K.Eristavi National Center of Experimental and Clinical Surgery"	Tbilisi		Georgia
3	LTD M.Zodelava Hematology Centre	Tbilisi		Georgia
4	LTD Medinvest - Institute of Hematology and Transfusiology	Tbilisi		Georgia
5	Gabinet Lekarski, Bartosz Korczowski	Rzeszów		Poland
6	Regional Clinical Hospital	Kemerovo		Russian Federation
7	FGU Kirov Scientific Research	Kirov		Russian Federation
8	Center for Hemophilia Treatment	Saint Petersburg		Russian Federation
9	Haemophilia Comprehensive Care Centre	Johannesburg		South Africa

Sponsors and Collaborators

• Catalyst Biosciences

Investigators

• Study Director: Howard Levy, MD, PhD, MMM, Catalyst Biosciences

Study Documents (Full-Text)

• Study Protocol - Aug 25, 2018
• Statistical Analysis Plan - Nov 5, 2018

More Information

Publications

None provided.

• Responsible Party: Catalyst Biosciences
• ClinicalTrials.gov Identifier: NCT03407651
• Other Study ID Numbers: MAA-201
• First Posted: Jan 23, 2018
• Last Update Posted: Sep 23, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemophilia A; Hemophilia B

Study Results

Participant Flow

Recruitment Details	A total of 11 subjects participated in the study.

Arm/Group Title	Overall Study Population
Arm/Group Description	Period 1: Part 1a Coagulation Factor VIIa variant, 18 µg/kg by intravenous route Coagulation Factor VIIa variant: Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Period 2: Part 1b Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route Coagulation Factor VIIa variant: Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Period 3: Part 2 Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route Coagulation Factor VIIa variant: Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.
Period Title: Period 1: Part 1a
STARTED	11
COMPLETED	10
NOT COMPLETED	1
Period Title: Period 1: Part 1a
STARTED	9
COMPLETED	9
NOT COMPLETED	0
Period Title: Period 1: Part 1a
STARTED	11
COMPLETED	8
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Safety Population
Arm/Group Description	Safety Population
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.0 (9.21)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	11 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.57 (11.061)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.05 (21.255)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.091 (5.1478)

Outcome Measures

1. Primary Outcome

Title	Bleeding Episode Prevention Success
Description	Annualized bleed rate (ABR; spontaneous and total) during Part 2 when on final MarzAA dose level versus recorded historical ABR. The analysis of the primary endpoint (annualized bleeding rate ABR for spontaneous and traumatic bleeds) of the final dose of MarzAA each subject was treated was based on the 1-sample test compared to a predefined rate assumed for the on-demand therapy. The latter was assumed to be 12 (or 1 bleed per month), which was the minimum ABR for each subject according to inclusion criterion 2 (defined as the H0), with no maximum value. A higher score indicated a worse outcome. ABR is on a scale of 0 to 365, with a lower score reflective of a lower number of bleeding events in a year.
Time Frame	Day 1 of final MarzAA dose level - Day 50

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 2
Arm/Group Description	MarzAA 30 and 60 µg/kg by subcutaneous route Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.
Measure Participants	10
Mean (Standard Deviation) [score on a scale]	1.4640 (3.08638)

2. Secondary Outcome

Title	Occurrence of Breakthrough Bleeding
Description	Occurrence of breakthrough bleeds requiring escalation to higher dose level
Time Frame	From Day 5 of dose level until occurrence of event

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a, MarzAA IV 18 µg/kg	Part 1b, MarzAA SC 30 µg/kg	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	Single intravenous injection of MarzAA 18 µg/kg	Single subcutaneous injection of MarzAA 30 µg/kg	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	10	9	11	2
Number [number of breakthrough bleeds]	0	0	5	0

3. Secondary Outcome

Title	Occurrence of Clinical Thrombotic Event
Description	Occurrence of clinical thrombotic event not attributable to another cause
Time Frame	From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1, MarzAA IV 18 µg/kg	Part 1, MarzAA SC 30 µg/kg	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	Single intravenous infusion of MarzAA 18 µg/kg	Single subcutaneous infusion of MarzAA 30 µg/kg	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	10	9	11	2
Number [number of events]	0	0	0	0

4. Secondary Outcome

Title	Coagulation Assessment - Prothrombin Time
Description	Change in coagulation parameter (prothrombin time [PT]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Time Frame	From date of pre-dose to 24 hours (Part 1a), pre-dose to 48 hours (Part 1b), and pre-dose to Day 50 (Part 2)

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a, MarzAA IV 18 µg/kg	Part 1b, MarzAA SC 30 µg/kg	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	Single intravenous infusion of MarzAA 18 µg/kg	Single subcutaneous infusion of MarzAA 30 µg/kg	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	10	9	10	2
Median (Full Range) [seconds]	-3.70	-2.80	-3.0	-4.80

5. Secondary Outcome

Title	Coagulation Assessment - Activated Partial Thromboplastin Time
Description	Change in coagulation parameter (activated partial thromboplastin time [aPTT]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Time Frame	From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2)

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a, MarzAA IV 18 µg/kg	Part 1b, MarzAA SC 30 µg/kg	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	Single intravenous infusion of MarzAA 18 µg/kg	Single subcutaneous infusion of MarzAA 30 µg/kg	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	9	9	10	2
Median (Full Range) [seconds]	-10.60	1.30	-8.30	-15.00

6. Secondary Outcome

Title	Coagulation Assessment - Fibrinogen
Description	Change in coagulation parameter (fibrinogen) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Time Frame	From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2).

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a	Part 1b	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 ug/kg
Arm/Group Description	MarzAA 18 µg/kg by intravenous injection	MarzAA 30 µg/kg by subcutaneous injection	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	9	9	10	2
Median (Full Range) [mg/dL]	-10.0	-15.00	-4.0	-4.0

7. Secondary Outcome

Title	Number of Events of Antibody Formation
Description	Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII) or Factor VII activated (FVIIa)
Time Frame	From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a	Part 1b	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	MarzAA 18 µg/kg by intravenous injection	MarzAA 30 µg/kg by subcutaneous injection	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	10	9	11	2
Number [number of events of antibody formation]	0	0	0	0

8. Secondary Outcome

Title	Number of Events of an Antibody Response
Description	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.
Time Frame	From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50.

Outcome Measure Data

Analysis Population Description

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required. Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a	Part 1b	Part 2, MarzAA 30 µg/kg	Part 2, MarzAA 60 µg/kg
Arm/Group Description	MarzAA 18 µg/kg by intravenous injection	MarzAA 30 µg/kg by subcutaneous injection	MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Measure Participants	10	9	11	2
Number [number of events of antibody response]	0	0	0	0

9. Secondary Outcome

Title	Thrombogenicity Assessment
Description	Number of participants with clinically significant levels of thrombogenicity markers (D-dimer, Prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex [TAT]), based on standard laboratory tests and clinical examination with a specific search for any signs of thrombosis
Time Frame	From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed was based on the Intent-to-Treat Population.

Arm/Group Title	Part 1a, MarzAA IV 18 µg/kg	Part 1b, MarzAA SC 30 µg/kg
Arm/Group Description	MarzAA 18 ug/kg by intravenous injection	MarzAA 30 ug/kg by subcutaneous injection
Measure Participants	10	9
Number [participants]	0 0%	0 NaN

Adverse Events

Time Frame	Members of the study team recorded all reportable events with start dates occurring any time after informed consent was obtained until study completion, or discharge, for non-serious AEs and until 30 days after the last day of study participation for SAEs. The duration of the study was 52 days.
Adverse Event Reporting Description	Adverse events and serious adverse events are based on the Safety Population.
Arm/Group Title	MarzAA IV 18 μg/kg		MarzAA SC 30 μg/kg		MarzAA 30 ug/kg		MarzAA 60 ug/kg
Arm/Group Description	IV infusion of 18 ug/kg MarzAA, Part 1 of study		SC infusion of MarzAA SC 30 μg/kg, Part 1 of study		SC infusion of MarzAA 30 ug/kg, Part 2 of study		SC infusion of MarzAA 60 ug/kg, Part 2 of study
All Cause Mortality
	MarzAA IV 18 μg/kg		MarzAA SC 30 μg/kg		MarzAA 30 ug/kg		MarzAA 60 ug/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		1/10 (10%)		0/2 (0%)
Serious Adverse Events
	MarzAA IV 18 μg/kg		MarzAA SC 30 μg/kg		MarzAA 30 ug/kg		MarzAA 60 ug/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		1/10 (10%)		0/2 (0%)
Nervous system disorders
Haemorrhagic stroke	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Vascular disorders
Hypertension	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	MarzAA IV 18 μg/kg		MarzAA SC 30 μg/kg		MarzAA 30 ug/kg		MarzAA 60 ug/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		1/9 (11.1%)		8/10 (80%)		1/2 (50%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)	0	0/9 (0%)	0	2/10 (20%)	2	0/2 (0%)	0
Eye disorders
Blepharitis	0/10 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/2 (50%)	1
Gastrointestinal disorders
Dyspepsia	0/10 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/2 (50%)	1
Vomiting	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
General disorders
Injection site reaction	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	5	0/2 (0%)	0
Infections and infestations
Respiratory tract infection	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	10	0/2 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Haemarthrosis	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Nervous system disorders
Headache	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Haemorrhagic stroke	0/10 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Psychiatric disorders
Panic attack	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Vascular disorders
Haematoma	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Haemorrhagic vasculitis	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Hypertension	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0

Limitations/Caveats

A planned outcome measure (coagulation assessment via MarzAA activity levels) of the protocol was not calculated as as a satisfactory assay could not be developed. Data is not reported for two allowed dose groups in Part 2, MarzAA 90 μg and 120 μg, as no subjects were treated at these dose levels

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.