Phase 1
N=11
Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
Hemophilia A · Hemophilia B · Hemophilia A With Inhibitor · Hemophilia B With Inhibitor · Hemophilia A Without Inhibitor
Bottom Line
View on ClinicalTrials.gov: NCT04072237 ↗Enrolled (actual)
11
Serious AEs
0.0%
Results posted
Jul 2021
Primary outcome: Primary: Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last — 1390.0; 516.4; 849.4; 1060.0 h*ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MarzAA (marzeptacog alfa [activated]) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Catalyst Biosciences
- Primary completion
- Apr 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last |
1390.0; 516.4; 849.4; 1060.0; 1025.6; 1487.9 | — |
| PRIMARY Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose |
76.81; 14.32; 15.40; 15.37; 15.57; 14.70 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax |
419.49; 18.96; 32.91; 41.88; 40.75; 54.29 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax |
0.17; 7.50; 7.38; 8.25; 6.75; 7.12 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα |
1.73; NA; NA; NA; NA; NA | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z |
3.3; 18.55; 19.26; 15.70; 13.05; 15.50 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - CL |
14.22; 63.33; 57.85; 58.88; 63.92; 65.13 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1 |
53.41; 1868.28; 1651.05; 1400.41; 1344.19; 1577.63 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs |
100; 19.47; 21.52; 21.32; 20.87; 19.84 | — |
| SECONDARY Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time |
3.77; 28.25; 28.10; 23.79; 20.96; 23.42 | — |
| SECONDARY Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose |
15.3687; 15.5688 | — |
| SECONDARY Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc |
1060.0; 1025.6; 922.1; 934.1 | — |
| SECONDARY Change in Coagulation Parameters - Prothrombin Time (PT) |
-1.36; -1.41; -1.16; -1.09; -1.29; -1.07 | — |
| SECONDARY Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT) |
-11.69; 1.91; -2.33; -2.18; -2.51; -2.85 | — |
| SECONDARY Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak |
64.0; 14.9; 28.3; 42.3; 45.4; 33.0 | — |
| SECONDARY Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak |
-1.30; -1.21; -1.11; -1.42; -1.38; -1.07 | — |
| SECONDARY Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential |
215.9; 158.6; 94.3; 149.5; 211.0; 133.0 | — |
| SECONDARY Change in Thrombogenicity Parameter - Fibrinogen |
-13.2; 13.3; -23.6; 16.0; 7.6; -31.0 | — |
| SECONDARY Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2 |
1903.5; 206.3; 56.0; 76.5; 383.9; 974.5 | — |
| SECONDARY Change in Thrombogenicity Parameter - Thrombin/Antithrombin |
105.09; 62.34; 10.41; 63.57; 138.19; 56.79 | — |
| SECONDARY Change in Thrombogenicity Parameter - D-Dimer |
0.141; -0.054; 0.110; 0.039; 0.285; 0.200 | — |
| SECONDARY Occurrence of an Antibody Response to MarzAA |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Occurrence of Clinical Thrombotic Event |
0; 0; 0; 0; 0; 0 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04072237). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.