Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
Sponsor
Catalyst Biosciences (Industry)
Overall Status
Completed
CT.gov ID
NCT04072237
Collaborator
(none)
11
5
1
8.8
2.2
0.3
Study Details
Study Description
Brief Summary
This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor. The study will enroll at least 8 adult male subjects with moderate or severe Hemophilia A or B with or without an inhibitor, in each dosing stage. Each subject will receive escalating doses of MarzAA for each stage of the study (except for Stage 5, where subjects receive the same dose as in Stage 4 split between two anatomical sites).
Study Design
Study Type:
Interventional
Actual Enrollment
:
11 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Phase 1 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Ascending Doses of Subcutaneous Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
Actual Study Start Date
:
Sep 24, 2019
Actual Primary Completion Date
:
Apr 30, 2020
Actual Study Completion Date
:
Jun 17, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study Population 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])
Single intravenous dose and ascending doses of subcutaneous injection of MarzAA (Coagulation Faction VIIa Variant)
|
Outcome Measures
Primary Outcome Measures
- Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last [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 pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups
- Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose [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 pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups
Secondary Outcome Measures
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax [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.]
Change in Cmax at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax [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.]
Change in Tmax at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα [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.]
Change in T1/2eqα at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z [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.]
Change in T1/2λ-z at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - CL [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.]
Change in CL at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1 [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.]
Change in Vd1 at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs [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.]
Change in BAabs at each stage for each dose group
- Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time [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.]
Change in Mean Residence Time at each stage for each dose group
- Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose [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.]
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)
- Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc [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.]
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)
- Change in Coagulation Parameters - Prothrombin Time (PT) [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).]
Maximum change in PT from pre-dose
- Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT) [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in aPTT from pre-dose
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in TGT parameter from pre-dose
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in TGT parameters from pre-dose
- Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in TGT parameter from pre-dose
- Change in Thrombogenicity Parameter - Fibrinogen [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in thrombogenicity parameter from pre-dose
- Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2 [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in thrombogenicity parameter from pre-dose
- Change in Thrombogenicity Parameter - Thrombin/Antithrombin [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in thrombogenicity parameter from pre-dose
- Change in Thrombogenicity Parameter - D-Dimer [From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).]
Maximum change in thrombogenicity parameter from pre-dose
- Occurrence of an Antibody Response to MarzAA [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.]
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
- Occurrence of Clinical Thrombotic Event [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.]
Occurrence of clinical thrombotic event not attributable to another cause
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Moderate or severe congenital Hemophilia A or B, with or without an inhibitor
-
Male, age 18 or older
-
Affirmation of informed consent with signature confirmation before any trial related activities
Exclusion Criteria:
-
Inability to discontinue and washout prophylaxis treatment 72 hours prior to dosing.
-
Previous participation in a trial involving SC Administration of rFVIIa or any trial using a modified amino-acid sequence FVIIa
-
Known positive antibody to FVII or FVIIa detected by central laboratory at screening
-
Have a coagulation disorder other than hemophilia A or B, with or without an inhibitor
-
Significant contraindication to participate
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical Center "Hippocrates - N" | Plovdiv | Bulgaria | ||
| 2 | Specialized Hospital for Active Treatment of Hematological Diseases | Sofia | Bulgaria | ||
| 3 | Kirov Research Institute of Hematology and Blood Transfusion | Kirov | Russian Federation | ||
| 4 | National Medical Hematology Research Center | Moscow | Russian Federation | ||
| 5 | Municipal Policlinic # 37, City Center for Hemophilia Treatment | Saint Petersburg | Russian Federation |
Sponsors and Collaborators
- Catalyst Biosciences
Investigators
- Study Director: Howard Levy, MD, PhD, MMM, Sponsor GmbH
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Catalyst Biosciences
ClinicalTrials.gov Identifier:
NCT04072237
Other Study ID Numbers:
- MAA-102
First Posted:
Aug 28, 2019
Last Update Posted:
Sep 13, 2021
Last Verified:
Sep 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:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Fourteen subjects were screened in the study and three subjects were screen failures. Two subjects failed due to having a known positive antibody at screening, and one subject failed screening due to other. |
| Arm/Group Title | Overall Study Population |
|---|---|
| Arm/Group Description | Coagulation Factor VIIa variant: Single intravenous dose and ascending doses of subcutaneous injection of MarzAA |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 11 |
| COMPLETED | 10 |
| NOT COMPLETED | 1 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
| Period Title: Stage I: MarzAA 18 µg/kg IV | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Study Population |
|---|---|
| Arm/Group Description | 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) |
| Overall Participants | 11 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
11
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
11
100%
|
| 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%
|
| Region of Enrollment (participants) [Number] | |
| Bulgaria |
8
72.7%
|
| Russia |
3
27.3%
|
Outcome Measures
| Title | Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last |
|---|---|
| Description | Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| AUC0-∞ |
1390.0
(433.99)
|
516.4
(170.01)
|
849.4
(275.00)
|
1060.0
(205.86)
|
1025.6
(328.31)
|
1487.9
(429.39)
|
2087.6
(648.85)
|
2108.0
(409.00)
|
3235.5
(735.43)
|
| AUC0-last |
1382.6
(431.45)
|
429.5
(178.30)
|
692.9
(232.53)
|
922.1
(192.38)
|
934.1
(305.32)
|
1322.6
(440.03)
|
1868.1
(651.04)
|
1939.1
(357.25)
|
3038.1
(760.56)
|
| Title | Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose |
|---|---|
| Description | Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [h*kg/mL] |
76.81
(23.97)
|
14.32
(5.94)
|
15.40
(5.17)
|
15.37
(3.206)
|
15.57
(5.09)
|
14.70
(4.89)
|
15.57
(5.43)
|
16.16
(2.98)
|
16.88
(4.23)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax |
|---|---|
| Description | Change in Cmax at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [ng/mL] |
419.49
(185.18)
|
18.96
(10.29)
|
32.91
(18.49)
|
41.88
(15.24)
|
40.75
(15.98)
|
54.29
(24.68)
|
76.70
(34.51)
|
68.04
(26.58)
|
98.33
(32.64)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax |
|---|---|
| Description | Change in Tmax at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [hour] |
0.17
(0.29)
|
7.50
(1.60)
|
7.38
(2.56)
|
8.25
(1.39)
|
6.75
(1.398)
|
7.12
(1.55)
|
8.25
(1.39)
|
8.37
(2.67)
|
12.25
(5.04)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα |
|---|---|
| Description | Change in T1/2eqα at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [hours] |
1.73
(0.55)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z |
|---|---|
| Description | Change in T1/2λ-z at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [hours] |
3.3
(0.38)
|
18.55
(5.88)
|
19.26
(6.69)
|
15.70
(3.45)
|
13.05
(5.07)
|
15.50
(5.65)
|
15.03
(4.43)
|
18.82
(5.82)
|
18.07
(6.78)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - CL |
|---|---|
| Description | Change in CL at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [mL/h] |
14.22
(4.66)
|
63.33
(19.64)
|
57.85
(18.21)
|
58.88
(13.68)
|
63.92
(20.36)
|
65.13
(18.67)
|
64.39
(26.93)
|
59.05
(12.68)
|
58.22
(13.28)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1 |
|---|---|
| Description | Change in Vd1 at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [mL] |
53.41
(18.02)
|
1868.28
(962.02)
|
1651.05
(799.32)
|
1400.41
(478.92)
|
1344.19
(557.26)
|
1577.63
(791.28)
|
1509.24
(796.50)
|
1699.49
(474.39)
|
1717.33
(629.45)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs |
|---|---|
| Description | Change in BAabs at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [Percentage] |
100
(100)
|
19.47
(8.07)
|
21.52
(10.63)
|
21.32
(7.42)
|
20.87
(6.32)
|
19.84
(7.20)
|
21.24
(9.32)
|
23.00
(8.98)
|
23.32
(6.69)
|
| Title | Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time |
|---|---|
| Description | Change in Mean Residence Time at each stage for each dose group |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [hours] |
3.77
(0.42)
|
28.25
(9.18)
|
28.10
(9.94)
|
23.79
(5.40)
|
20.96
(5.58)
|
23.42
(7.47)
|
22.80
(5.9211)
|
29.04
(7.88)
|
29.32
(8.60)
|
| Title | Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose |
|---|---|
| Description | 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) |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 4 MarzAA 60μg/kg SC | Stage 5 MarzAA 2×30μg/kg SC |
|---|---|---|
| Arm/Group Description | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant |
| Measure Participants | 8 | 8 |
| Mean (Standard Deviation) [h*kg/mL] |
15.3687
(3.20630)
|
15.5688
(5.08859)
|
| Title | Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc |
|---|---|
| Description | 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) |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 4 MarzAA 60μg/kg SC | Stage 5 MarzAA 2×30μg/kg SC |
|---|---|---|
| Arm/Group Description | Single subcutaneous injection of MarzAA coagulation factor VIIa variant | Two subcutaneous injections of MarzAA coagulation factor VIIa variant |
| Measure Participants | 8 | 8 |
| AUC Infinity Obs |
1060.0
(205.86)
|
1025.6
(328.31)
|
| AUC to Last Nonzero Conc |
922.1
(192.38)
|
934.1
(305.32)
|
| Title | Change in Coagulation Parameters - Prothrombin Time (PT) |
|---|---|
| Description | Maximum change in PT from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [seconds] |
-1.36
(0.57)
|
-1.41
(0.86)
|
-1.16
(0.68)
|
-1.09
(0.58)
|
-1.29
(0.86)
|
-1.07
(0.79)
|
-1.37
(0.54)
|
-1.36
(0.60)
|
-1.35
(0.62)
|
| Title | Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT) |
|---|---|
| Description | Maximum change in aPTT from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [seconds] |
-11.69
(3.71)
|
1.91
(3.21)
|
-2.33
(4.28)
|
-2.18
(2.63)
|
-2.51
(2.09)
|
-2.85
(1.82)
|
-2.10
(3.02)
|
-2.92
(3.01)
|
-5.13
(2.59)
|
| Title | Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak |
|---|---|
| Description | Maximum change in TGT parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [nM] |
64.0
(65.32)
|
14.9
(31.69)
|
28.3
(21.04)
|
42.3
(32.13)
|
45.4
(30.84)
|
33.0
(25.16)
|
44.3
(46.10)
|
45.6
(19.18)
|
41.3
(30.47)
|
| Title | Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak |
|---|---|
| Description | Maximum change in TGT parameters from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two single subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| TGT-Lag |
-1.30
(1.231)
|
-1.21
(0.613)
|
-1.11
(0.391)
|
-1.42
(0.645)
|
-1.38
(0.311)
|
-1.07
(0.655)
|
-1.33
(0.396)
|
-1.54
(0.507)
|
-1.13
(0.688)
|
| TGT-Time to Peak |
-3.88
(3.302)
|
-2.22
(2.309)
|
-2.76
(1.226)
|
-3.53
(2.313)
|
-3.68
(1.290)
|
-3.73
(1.926)
|
-3.73
(2.024)
|
-3.70
(1.681)
|
-3.25
(1.756)
|
| Title | Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential |
|---|---|
| Description | Maximum change in TGT parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [nM•minutes] |
215.9
(337.55)
|
158.6
(247.55)
|
94.3
(148.51)
|
149.5
(256.34)
|
211.0
(190.22)
|
133.0
(193.85)
|
216.9
(184.54)
|
164.6
(58.49)
|
-187.3
(474.61)
|
| Title | Change in Thrombogenicity Parameter - Fibrinogen |
|---|---|
| Description | Maximum change in thrombogenicity parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [mg/dL] |
-13.2
(23.83)
|
13.3
(29.65)
|
-23.6
(34.04)
|
16.0
(37.67)
|
7.6
(51.69)
|
-31.0
(42.02)
|
21.6
(56.61)
|
-12.5
(32.74)
|
-8.0
(33.72)
|
| Title | Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2 |
|---|---|
| Description | Maximum change in thrombogenicity parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [pmol/L] |
1903.5
(3809.47)
|
206.3
(545.97)
|
56.0
(158.02)
|
76.5
(118.78)
|
383.9
(324.41)
|
974.5
(2407.09)
|
1744.9
(4367.48)
|
236.5
(459.58)
|
284.9
(672.80)
|
| Title | Change in Thrombogenicity Parameter - Thrombin/Antithrombin |
|---|---|
| Description | Maximum change in thrombogenicity parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [µg/L] |
105.09
(254.951)
|
62.34
(156.899)
|
10.41
(19.586)
|
63.57
(181.409)
|
138.19
(202.946)
|
56.79
(146.603)
|
10.46
(15.648)
|
18.90
(38.191)
|
3.75
(3.231)
|
| Title | Change in Thrombogenicity Parameter - D-Dimer |
|---|---|
| Description | Maximum change in thrombogenicity parameter from pre-dose |
| Time Frame | From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC). |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Mean (Standard Deviation) [mg/L Fibrinogen Equivalent Unit] |
0.141
(0.214)
|
-0.054
(0.104)
|
0.110
(0.080)
|
0.039
(0.073)
|
0.285
(0.605)
|
0.200
(0.175)
|
0.211
(0.285)
|
0.111
(0.125)
|
0.256
(0.173)
|
| Title | Occurrence of an Antibody Response to MarzAA |
|---|---|
| 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 End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg SC Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Number [participants with an occurrence] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Occurrence of Clinical Thrombotic Event |
|---|---|
| Description | Occurrence of clinical thrombotic event not attributable to another cause |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg IV | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 2×60 µg/kg SC Q3H | Stage 9 3×60 µg/kg Q3H |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous dose of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Single subcutaneous injection of MarzAA, coagulation factor VIIa variant | Two subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours | Three subcutaneous injections of MarzAA, coagulation factor VIIa variant, every 3 hours |
| Measure Participants | 10 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
| Number [participants with an occurrence] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| Time Frame | Treatment-emergent adverse events were defined as any event that either began or worsened after the first administration of study drug and within 28 days of the last dose. | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, without any judgment about causality. An AE could arise from any use of the drug (eg, off label use, use in combination with another drug) and from any route of administration, formulation, or dose, including an overdose. | |||||||||||||||||
| Arm/Group Title | Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 MarzAA 2×60 µg/kg SC Q3H | Stage 9 MarzAA 3×60 µg/kg SC Q3H | |||||||||
| Arm/Group Description | Single intravenous dose of MarzAA | Single subcutaneous injection of MarzAA | Single subcutaneous injection of MarzAA | Single subcutaneous injection of MarzAA | Two subcutaneous injections of MarzAA | Single subcutaneous injection of MarzAA | Single subcutaneous injection of MarzAA | Two subcutaneous injections of MarzAA every 3 hours | Three subcutaneous injections of MarzAA every 3 hours | |||||||||
All Cause Mortality |
||||||||||||||||||
| Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 MarzAA 2×60 µg/kg SC Q3H | Stage 9 MarzAA 3×60 µg/kg SC Q3H | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 MarzAA 2×60 µg/kg SC Q3H | Stage 9 MarzAA 3×60 µg/kg SC Q3H | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Stage 1 MarzAA 18 µg/kg SC | Stage 2 MarzAA 30 µg/kg SC | Stage 3 MarzAA 45 µg/kg SC | Stage 4 MarzAA 60 µg/kg SC | Stage 5 MarzAA 2×30 µg/kg SC | Stage 6 MarzAA 90 µg/kg SC | Stage 7 MarzAA 120 µg/kg SC | Stage 8 MarzAA 2×60 µg/kg SC Q3H | Stage 9 MarzAA 3×60 µg/kg SC Q3H | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 3/8 (37.5%) | 0/8 (0%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/8 (0%) | 2/8 (25%) | 3/8 (37.5%) | 2/8 (25%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/11 (0%) | 0 | 1/8 (12.5%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 |
| General disorders | ||||||||||||||||||
| Injection site reaction | 0/11 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 2/8 (25%) | 2 | 3/8 (37.5%) | 4 | 2/8 (25%) | 2 |
| Pyrexia | 0/11 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 |
| Infections and infestations | ||||||||||||||||||
| Nasopharyngitis | 0/11 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 |
Limitations/Caveats
[Not Specified]
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.
Results Point of Contact
| Name/Title | Howard Levy, Chief Medical Officer |
|---|---|
| Organization | Catalyst Biosciences |
| Phone | +1.650.266.6871 |
| hlevy@catbio.com |
Responsible Party:
Catalyst Biosciences
ClinicalTrials.gov Identifier:
NCT04072237
Other Study ID Numbers:
- MAA-102
First Posted:
Aug 28, 2019
Last Update Posted:
Sep 13, 2021
Last Verified:
Sep 1, 2021