A Clinical Trial of Study Medicine (Marstacimab) in Pediatric Patients With Hemophilia A or Hemophilia B

JRCT ID: jRCT2071220116

Registered date:14/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hemophilia A Hemophilia B
• Date of first enrollment: 18/07/2023
• Target sample size: 100
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Brazil,Japan,Canada,Japan,China,Japan,Denmark,Japan,France,Japan,Germany,Japan,India,Japan,Israel,Japan,Italy,Japan,Korea, Republic of,Japan,Saudi Arabia,Japan,Slovakia,Japan,South Africa,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: marstacimab
marstacimab
Other Name: PF-06741086

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Annualized bleeding rate (ABR) of treated bleeding events [ Time Frame: Baseline to end of 12-month treatment period ]
Derived for each subject for each period (historical and study treatment) by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25)
2.Incidence of adverse events and serious adverse events [ Time Frame: Screening through end of follow-up period (approximately 14 months) ]
3.Incidence and severity of thrombotic events [ Time Frame: Baseline to end of 12-month treatment period ]
4.Incidence and severity of thrombotic microangiopathy [ Time Frame: Baseline to end of 12-month treatment period ]
5.Incidence and severity of disseminated intravascular coagulation/consumption coagulopathy events [ Time Frame: Baseline to end of 12-month treatment period ]
6.Immunogenicity (incidence of ADA and clinically significant persistent NAb against marstacimab) [ Time Frame: Baseline to end of 12-month treatment period ]
7.Incidence and severity of injection site reaction [ Time Frame: Baseline to end of 12-month treatment period ]
8.Incidence of severe hypersensitivity and anaphylactic reactions [ Time Frame: Baseline to end of 12-month treatment period ]

Secondary Outcome

Secondary Outcome Measures :
1.Incidence of joint bleeds (treated) [ Time Frame: Baseline to end of 12-month treatment period ]
2.Incidence of spontaneous bleeds (treated) [ Time Frame: Baseline to end of 12-month treatment period ]
3.Incidence of target joint bleeds (treated) [ Time Frame: Baseline to end of 12-month treatment period ]
4.Incidence of total bleeds (treated and untreated) [ Time Frame: Baseline to end of 12-month treatment period ]
5.Number of target joints [ Time Frame: Baseline to end of 12-month treatment period ]
6.Change from baseline in joint health as measured by the HJHS for participants >=4 years of age [ Time Frame: Baseline to end of 12-month treatment period ]
7.Changes in quality of life measured by Haem-A-QoL/Haemo-QoL (using age-dependent versions for participants >=8 years of age) [ Time Frame: Baseline to end of 12-month treatment period ]
8.Changes in quality of life measured by pedHAL (using age-dependent versions for participants >=4 years of age) [ Time Frame: Baseline to end of 12-month treatment period ]
9.Changes in quality of life measured by Patient Global Impression of Change - Hemophilia for participants >=4 years of age [ Time Frame: Baseline to end of 12-month treatment period ]
10.Changes in quality of life measured by Health Utilities Measure (EQ-5D-Y) for participants >=4 years of age [ Time Frame: Baseline to end of 12-month treatment period ]

Key inclusion & exclusion criteria

• Age minimum: >= 1age old
• Age maximum: < 18age old
• Gender: Male

Include criteria

Inclusion Criteria:
*Male participants of appropriate age and required minimum weight
*Participants aged 12 to 17 years must be at least 25 kgs at time of consent.
*Participants aged 6 to 11 years must be at least 19 kgs at time of consent.
*Minimum weight requirement for participants aged 1 to 5 years is to be determined.
*Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B
*Participants must have at least 1 year of diary and/or medical records available in which exogenous FVIII or FIX replacement or bypass agent infusions and hemophilic bleeding episodes were consistently documented over the 12 months prior to the time of consent.
Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:
*No current detectable inhibitor and no documented history of inhibitors in the 5 years prior to consent
*Must have at least 50 exposure days to FVIII/FIX replacement products
*Must be at least 80% compliant with a stable and effective routine prophylaxis regimen with FVIII/FIX replacement products, for at least 12 months prior to consent
Participants who are enrolled into the Inhibitor Cohort must also meet the following criteria:
*Documentation of current high titer inhibitor (>=5 BU/mL); or current low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX recovery <60% of expected within previous 12 months prior to the time of consent
*Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the high quantitative inhibitor criteria described in the prior bullet at the time of screening (eg, participant with a previously documented high-titer inhibitor >=5 BU/mL) and whose condition precludes re-challenge with FVIII or FIX replacement may be considered for eligibility on a case-by-case basis with discussion and agreement from the Pfizer medical monitor.
*Hemophilia A participants with on-demand treatment regimen with >=12 bleeding episodes or hemophilia B participants with on-demand treatment regimen with >=8 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor in the 12 months prior to informed consent
*Participants must be on an on-demand bypass treatment regimen during the 12 months prior to informed consent

Exclude criteria

Exclusion Criteria:
*Known coronary artery, thrombotic, or ischemic disease, including congenital or acquired thrombophilic disease such as Anti-thrombin III, Factor V Leiden mutation, prothrombin 20210 mutation, protein C activity, protein S activity and antiphospholipid syndrome
*Known planned surgical procedure during the planned study period
*Known hemostatic defect other than hemophilia A or B
*Abnormal hematology, renal or hepatic function laboratory results at screening
*Other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator
*Individuals with known allergic reaction or hypersensitivity to hamster protein or other components of the study intervention
*Current routine prophylaxis with bypassing agent, non-coagulation non-factor replacement therapy (eg, emicizumab), or any previous treatment with a gene therapy product for treatment of hemophilia
*Participants with inhibitors who are being treated using a prophylaxis treatment regimen with a bypass agent, and, participants who have previously received non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) will be considered on a case-by-case basis, only after discussion and agreement between the investigator and the Pfizer medical monitor
*Regular use of immunomodulatory medications (eg, IVIG, routine systemic corticosteroids, rituximab)
*Use of systemic antifibrinolytics, medications that may increase the risk of bleeding, and certain non-steroidal anti-inflammatory drugs within 120 hours of first dose of study intervention and while on study
*Ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention
*Participation in other studies involving investigational drug(s) or investigational vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation
*Previous exposure to marstacimab during participation in other marstacimab clinical studies
*CD4 cell count <=200/uL if HIV-positive
*Abnormal ECG of clinical relevance that may affect participant safety or interpretation of study results
*Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05611801