Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia

September 9, 2021 updated by: Catalyst Biosciences

Phase 1 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Ascending Doses of Subcutaneous Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Plovdiv, Bulgaria
        • Medical Center "Hippocrates - N"
      • Sofia, Bulgaria
        • Specialized Hospital for Active Treatment of Hematological Diseases
  • Russian Federation
      • Kirov, Russian Federation
        • Kirov Research Institute of Hematology and Blood Transfusion
      • Moscow, Russian Federation
        • National Medical Hematology Research Center
      • Saint Petersburg, Russian Federation
        • Municipal Policlinic # 37, City Center for Hemophilia Treatment

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last
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.
Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups
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 MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose
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.
Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups
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.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax
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.
Change in Cmax at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - Tmax
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.
Change in Tmax at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα
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.
Change in T1/2eqα at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z
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.
Change in T1/2λ-z at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - CL
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.
Change in CL at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - Vd1
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.
Change in Vd1 at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - BAabs
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.
Change in BAabs at each stage for each dose group
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 MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time
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.
Change in Mean Residence Time at each stage for each dose group
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.
Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose
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.

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)
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.
Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc
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.

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)
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 Coagulation Parameters - Prothrombin Time (PT)
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).
Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Thrombogenicity Parameter - Fibrinogen
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Thrombogenicity Parameter - Thrombin/Antithrombin
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Change in Thrombogenicity Parameter - D-Dimer
Time Frame: 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
From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Occurrence of an Antibody Response to MarzAA
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.
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 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
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.
Occurrence of clinical thrombotic event not attributable to another cause
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Catalyst Biosciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Howard Levy, MD, PhD, MMM, Sponsor GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 24, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 17, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 22, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 13, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MAA-102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is an open label study so each investigator will have full access to all study subject data that is entered into the database.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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