Trial Outcomes & Findings for Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B (NCT NCT03407651)

Last Updated: 2021-09-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Day 1 of final MarzAA dose level - Day 50

Results posted on

2021-09-23

Participant Flow

A total of 11 subjects participated in the study.

Participant milestones

Participant milestones
Measure	Overall Study Population 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 1: Part 1a STARTED	11
Period 1: Part 1a COMPLETED	10
Period 1: Part 1a NOT COMPLETED	1
Period 2: Part 1b STARTED	9
Period 2: Part 1b COMPLETED	9
Period 2: Part 1b NOT COMPLETED	0
Period 3: Part 2 STARTED	11
Period 3: Part 2 COMPLETED	8
Period 3: Part 2 NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Population n=11 Participants Safety Population
Age, Continuous	31.0 years STANDARD_DEVIATION 9.21 • n=11 Participants
Sex: Female, Male Female	0 Participants n=11 Participants
Sex: Female, Male Male	11 Participants n=11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=11 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=11 Participants
Race (NIH/OMB) Asian	0 Participants n=11 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=11 Participants
Race (NIH/OMB) Black or African American	0 Participants n=11 Participants
Race (NIH/OMB) White	11 Participants n=11 Participants
Race (NIH/OMB) More than one race	0 Participants n=11 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=11 Participants
Height	171.57 cm STANDARD_DEVIATION 11.061 • n=10 Participants • Safety Population
Weight	69.05 kg STANDARD_DEVIATION 21.255 • n=10 Participants • Safety Population
BMI	23.091 kg/m^2 STANDARD_DEVIATION 5.1478 • n=10 Participants • Safety Population

PRIMARY outcome

Timeframe: Day 1 of final MarzAA dose level - Day 50

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

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Bleeding Episode Prevention Success	1.4640 score on a scale Standard Deviation 3.08638	—	—	—

SECONDARY outcome

Timeframe: From Day 5 of dose level until occurrence of event

Population: 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.

Occurrence of breakthrough bleeds requiring escalation to higher dose level

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=11 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Occurrence of Breakthrough Bleeding	0 number of breakthrough bleeds	0 number of breakthrough bleeds	5 number of breakthrough bleeds	0 number of breakthrough bleeds

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=11 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Occurrence of Clinical Thrombotic Event	0 number of events	0 number of events	0 number of events	0 number of events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=10 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Coagulation Assessment - Prothrombin Time	-3.70 seconds Interval -5.3 to 1.5	-2.80 seconds Interval -4.8 to -0.3	-3.0 seconds Interval -6.5 to 1.2	-4.80 seconds Interval -4.8 to 3.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=9 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=10 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Coagulation Assessment - Activated Partial Thromboplastin Time	-10.60 seconds Interval -57.4 to 140.8	1.30 seconds Interval -30.65 to 50.1	-8.30 seconds Interval -47.3 to 30.3	-15.00 seconds Interval -20.15 to 2.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=9 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=10 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Coagulation Assessment - Fibrinogen	-10.0 mg/dL Interval -173.0 to 51.0	-15.00 mg/dL Interval -133.0 to 108.0	-4.0 mg/dL Interval -112.0 to 146.0	-4.0 mg/dL Interval -84.0 to 116.0

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=11 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Number of Events of Antibody Formation	0 number of events of antibody formation	0 number of events of antibody formation	0 number of events of antibody formation	0 number of events of antibody formation

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg n=11 Participants MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg n=2 Participants MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Number of Events of an Antibody Response	0 number of events of antibody response	0 number of events of antibody response	0 number of events of antibody response	0 number of events of antibody response

SECONDARY outcome

Timeframe: From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.

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

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

Outcome measures

Outcome measures
Measure	Part 2 n=10 Participants 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.	Part 1b, MarzAA SC 30 µg/kg n=9 Participants Single subcutaneous injection of MarzAA 30 µg/kg	Part 2, MarzAA 30 µg/kg MarzAA 30 µg/kg by subcutaneous injection daily for 50 days	Part 2, MarzAA 60 µg/kg MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
Thrombogenicity Assessment	0 participants	0 participants	—	—

Adverse Events

MarzAA IV 18 μg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

MarzAA SC 30 μg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

MarzAA 30 ug/kg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 1 deaths

MarzAA 60 ug/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MarzAA IV 18 μg/kg n=10 participants at risk IV infusion of 18 ug/kg MarzAA, Part 1 of study	MarzAA SC 30 μg/kg n=9 participants at risk SC infusion of MarzAA SC 30 μg/kg, Part 1 of study	MarzAA 30 ug/kg n=10 participants at risk SC infusion of MarzAA 30 ug/kg, Part 2 of study	MarzAA 60 ug/kg n=2 participants at risk SC infusion of MarzAA 60 ug/kg, Part 2 of study
Nervous system disorders Haemorrhagic stroke	0.00% 0/10 • 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 events and serious adverse events are based on the Safety Population.	0.00% 0/9 • 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 events and serious adverse events are based on the Safety Population.	10.0% 1/10 • Number of events 1 • 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 events and serious adverse events are based on the Safety Population.	0.00% 0/2 • 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 events and serious adverse events are based on the Safety Population.
Vascular disorders Hypertension	0.00% 0/10 • 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 events and serious adverse events are based on the Safety Population.	0.00% 0/9 • 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 events and serious adverse events are based on the Safety Population.	10.0% 1/10 • Number of events 1 • 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 events and serious adverse events are based on the Safety Population.	0.00% 0/2 • 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 events and serious adverse events are based on the Safety Population.

Other adverse events

Additional Information

Howard Levy, Chief Medical Officer

Catalyst Biosciences

Phone: +1.650.266.6871

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place