Hemophilia A With InhibitorPhase 2NCT03407651
Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B
A Phase 2 study testing Coagulation Factor VIIa variant in people with Hemophilia A With Inhibitor and Hemophilia B With Inhibitor, run by Catalyst Biosciences at 9 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia A With Inhibitor, Hemophilia B With Inhibitor
- What is being tested?
- Coagulation Factor VIIa variant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 18 Dec 2017to 13 Apr 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe congenital hemophilia A or B with an inhibitor.
- History of frequent spontaneous bleeding episodes.
- Male, age 18 or older.
- Affirmation of informed consent with signature confirmation before any trial-related activities.
Who cannot join
- Receiving prophylaxis treatment.
- Previous participation in a clinical trial evaluating a modified rFVIIa agent.
- Known positive antibody to FVII or FVIIa detected by central laboratory at screening.
- Have a coagulation disorder other than hemophilia A or B.
- Significant contraindication to participation.
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Georgia3 sites
JSC "K.Eristavi National Center of Experimental and Clinical Surgery"
Tbilisi
LTD M.Zodelava Hematology Centre
Tbilisi
LTD Medinvest - Institute of Hematology and Transfusiology
Tbilisi
Russia3 sites
Regional Clinical Hospital
Kemerovo
FGU Kirov Scientific Research
Kirov
Center for Hemophilia Treatment
Saint Petersburg
About this study
Official title: Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of a Daily Subcutaneous Treatment Regimen With Marzeptacog Alfa (Activated) for Bleeding Prophylaxis in Adult Subjects With Hemophilia A and B Subjects With an Inhibitor
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.
Read the detailed description
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.
- Being tested
- Coagulation Factor VIIa variant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coagulation Factor VIIa variantBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Part 1a | Experimental | Coagulation Factor VIIa variant, 18 µg/kg by intravenous route Receives: Biological: Coagulation Factor VIIa variant |
| Part 1b | Experimental | Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route Receives: Biological: Coagulation Factor VIIa variant |
| Part 2 | Experimental | Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route Receives: Biological: Coagulation Factor VIIa variant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 of final MarzAA dose level - Day 50
Secondary outcomes (8)
Occurrence of Breakthrough Bleeding
Occurrence of breakthrough bleeds requiring escalation to higher dose level
Measured: From Day 5 of dose level until occurrence of event
Occurrence of Clinical Thrombotic Event
Occurrence of clinical thrombotic event not attributable to another cause
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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
Measured: From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start18 Dec 2017
- Primary completion15 Mar 2019
- Study completion13 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia A With InhibitorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catalyst Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Howard Levy, MD, PhD, MMM, Study director, Catalyst Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03407651
- Sponsor's protocol ID
- MAA-201
- Status last verified
- Jun 2021
- First submitted
- 4 Jan 2018
- Last updated
- 23 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: This is an open label study so each investigator will have full access to all study subject data that is entered into the database
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of a Daily Subcutaneous Treatment Regimen With Marzeptacog Alfa (Activated) for Bleeding Prophylaxis in Adult Subjects With Hemophilia A and B Subjects With an Inhibitor
- ClinicalTrials.gov ID
- NCT03407651
- Acronym / sponsor ID
- MAA-201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Catalyst BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 15 Mar 2019 (actual)
- Study completion
- 13 Apr 2019 (actual)
- First posted
- 23 Jan 2018 (actual)
- Results
- Posted 23 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1a | Experimental | Biological: Coagulation Factor VIIa variantCoagulation Factor VIIa variant, 18 µg/kg by intravenous route |
| Part 1b | Experimental | Biological: Coagulation Factor VIIa variantCoagulation Factor VIIa variant, 30 µg/kg by subcutaneous route |
| Part 2 | Experimental | Biological: Coagulation Factor VIIa variantCoagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Severe congenital hemophilia A or B with an inhibitor.
- History of frequent spontaneous bleeding episodes.
- Male, age 18 or older.
- Affirmation of informed consent with signature confirmation before any trial-related activities.
Key exclusion criteria (5 listed)
- Receiving prophylaxis treatment.
- Previous participation in a clinical trial evaluating a modified rFVIIa agent.
- Known positive antibody to FVII or FVIIa detected by central laboratory at screening.
- Have a coagulation disorder other than hemophilia A or B.
- Significant contraindication to participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coagulation Factor VIIa variantSingle 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. | Biological | Part 1a, Part 1b, Part 2 |
Primary outcome
Bleeding Episode Prevention Success
Time frame: Day 1 of final MarzAA dose level - Day 50
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.
8 secondary outcomes
Occurrence of Breakthrough Bleeding
Time frame: From Day 5 of dose level until occurrence of event
Occurrence of Clinical Thrombotic Event
Time frame: From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50
Coagulation Assessment - Prothrombin Time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50.
Thrombogenicity Assessment
Time frame: From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. This is an open label study so each investigator will have full access to all study subject data that is entered into the database
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard Levy, MD, PhD, MMM study director
Catalyst Biosciences
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Coagulation Factor VIIa variant in people with Hemophilia A With Inhibitor and Hemophilia B With Inhibitor, run by Catalyst Biosciences at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Georgia, Russia, Armenia, Poland, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bleeding Episode Prevention Success (time frame: Day 1 of final MarzAA dose level - Day 50). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2021.