Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1a | Experimental | Coagulation Factor VIIa variant, 18 µg/kg by intravenous route |
|
| Part 1b | Experimental | Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route |
|
| Part 2 | Experimental | Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Coagulation Factor VIIa variant | Biological | 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 | Description | Time Frame |
|---|---|---|
| Bleeding Episode Prevention Success | 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. | Day 1 of final MarzAA dose level - Day 50 |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Breakthrough Bleeding | Occurrence of breakthrough bleeds requiring escalation to higher dose level | From Day 5 of dose level until occurrence of event |
| Occurrence of Clinical Thrombotic Event |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Howard Levy, MD, PhD, MMM | Catalyst Biosciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hematology Center after Prof. R. Yeolyan | Yerevan | Armenia | ||||
| JSC "K.Eristavi National Center of Experimental and Clinical Surgery" |
This is an open label study so each investigator will have full access to all study subject data that is entered into the database
Not provided
Not provided
Not provided
Not provided
Not provided
A total of 11 subjects participated in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1: Part 1a |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 25, 2018 | Jun 25, 2021 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Occurrence of clinical thrombotic event not attributable to another cause
| From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50 |
| Coagulation Assessment - Prothrombin Time | 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. | 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) |
| Coagulation Assessment - Activated Partial Thromboplastin Time | 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. | From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2) |
| Coagulation Assessment - Fibrinogen | Change in coagulation parameter (fibrinogen) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints. | From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2). |
| Number of Events of Antibody Formation | Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII) or Factor VII activated (FVIIa) | From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50 |
| Number of Events of an Antibody Response | 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. | From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50. |
| Thrombogenicity Assessment | 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 | From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50. |
| Tbilisi |
| Georgia |
| LTD M.Zodelava Hematology Centre | Tbilisi | Georgia |
| LTD Medinvest - Institute of Hematology and Transfusiology | Tbilisi | Georgia |
| Gabinet Lekarski, Bartosz Korczowski | Rzeszów | Poland |
| Regional Clinical Hospital | Kemerovo | Russia |
| FGU Kirov Scientific Research | Kirov | Russia |
| Center for Hemophilia Treatment | Saint Petersburg | Russia |
| Haemophilia Comprehensive Care Centre | Johannesburg | South Africa |
| COMPLETED |
|
| NOT COMPLETED |
|
| Period 2: Part 1b |
|
| Period 3: Part 2 |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Safety Population | Safety Population |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Height | This assessment was not available for one subject in the study. | Safety Population | Mean | Standard Deviation | cm |
| |||||||||||||||
| Weight | This assessment was not available for one subject in the study. | Safety Population | Mean | Standard Deviation | kg |
| |||||||||||||||
| BMI | This assessment was not available for one subject in the study. | Safety Population | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Bleeding Episode Prevention Success | 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. | Overall number of participants analyzed was based on the Intent-to-Treat Population. | Posted | Mean | Standard Deviation | score on a scale | Day 1 of final MarzAA dose level - Day 50 |
|
|
| |||||||||||||||||||||||||
| Secondary | Occurrence of Breakthrough Bleeding | Occurrence of breakthrough bleeds requiring escalation to higher dose level | 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. | Posted | Number | number of breakthrough bleeds | From Day 5 of dose level until occurrence of event |
| ||||||||||||||||||||||||||||
| Secondary | Occurrence of Clinical Thrombotic Event | Occurrence of clinical thrombotic event not attributable to another cause | 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. | Posted | Number | number of events | From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50 |
| ||||||||||||||||||||||||||||
| Secondary | Coagulation Assessment - Prothrombin Time | 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. | 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. | Posted | Median | Full Range | seconds | 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) |
| |||||||||||||||||||||||||||
| Secondary | Coagulation Assessment - Activated Partial Thromboplastin Time | 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. | 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. | Posted | Median | Full Range | seconds | From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2) |
| |||||||||||||||||||||||||||
| Secondary | Coagulation Assessment - Fibrinogen | Change in coagulation parameter (fibrinogen) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints. | 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. | Posted | Median | Full Range | mg/dL | From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2). |
| |||||||||||||||||||||||||||
| Secondary | Number of Events of Antibody Formation | Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII) or Factor VII activated (FVIIa) | 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. | Posted | Number | 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 |
| ||||||||||||||||||||||||||||
| Secondary | Number of Events of an Antibody Response | 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. | 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. | Posted | Number | number of events of antibody response | From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50. |
| ||||||||||||||||||||||||||||
| Secondary | Thrombogenicity Assessment | 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 | Overall number of participants analyzed was based on the Intent-to-Treat Population. | Posted | Number | participants | From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50. |
|
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MarzAA IV 18 μg/kg | IV infusion of 18 ug/kg MarzAA, Part 1 of study | 0 | 10 | 0 | 10 | 1 | 10 |
| EG001 | MarzAA SC 30 μg/kg | SC infusion of MarzAA SC 30 μg/kg, Part 1 of study | 0 | 9 | 0 | 9 | 1 | 9 |
| EG002 | MarzAA 30 ug/kg | SC infusion of MarzAA 30 ug/kg, Part 2 of study | 1 | 10 | 1 | 10 | 8 | 10 |
| EG003 | MarzAA 60 ug/kg | SC infusion of MarzAA 60 ug/kg, Part 2 of study | 0 | 2 | 0 | 2 | 1 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemorrhagic stroke | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Blepharitis | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemorrhagic stroke | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Panic attack | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemorrhagic vasculitis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
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
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Howard Levy, Chief Medical Officer | Catalyst Biosciences | +1.650.266.6871 | hlevy@catbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 5, 2018 | Jun 25, 2021 | SAP_001.pdf |
Not provided
|
| Unknown or Not Reported |
|
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
|
|
MarzAA 60 µg/kg by subcutaneous injection daily if dose escalation required, up to Day 50
|
|
|
|
|
|
|
|
|