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Study of the Efficacy and Safety PF-06741086 in Adult and Teenage Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B

Basic Information

Recruitment status	recruiting
Health condition(s) or Problem(s) studied	Bleeding tendency in hemophilia A and B patients with and without inhibitors
Date of first enrollment	08/07/2020
Target sample size	145
Countries of recruitment	Japan,Asia except Japan,North America,South America,Europe,Oceania
Study type	Interventional
Intervention(s)	investigational material(s) Generic name etc : PF-06741086 (marstacimab): 150 mg (potency of 150 mg/mL) in a pre-filled syringe INN of investigational material : marstacimab Therapeutic category code : 634 Human blood preparations Dosage and Administration for Investigational material : Drug: PF-06741086 300 mg subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria. control material(s) Generic name etc : - INN of investigational material : - Therapeutic category code : Dosage and Administration for Investigational material : -

Outcome(s)

Primary Outcome

safety efficacy Annualized bleeding rate (ABR) of treated bleeding events [Time Frame: Through Observational Phase (6months) and Active Treatment Phase (12 months) for total of approximately 18 months] Derived for each subject for each treatment period by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25) Incidence and severity of thrombotic events [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Incidence of anti drug antibody [ADA] against PF-06741086 [Time Frame: Throughout Active Treatment Phase (12 months)] Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086 [Time Frame: Throughout Active Treatment Phase (12 months)] Incidence and severity of injection site reaction [Time Frame: Throughout Active Treatment Phase (12 months)] Number of participants with clinically significant changes from baseline in physical exam [Time Frame: From Baseline through Observation and Active Treatment (approximately 18 months)] Incidence of clinically significant laboratory value abnormalities [Time Frame: From Screening through Observation and Active Treatment (approximately 18 months)] Incidence of severe hypersensitivity and anaphylactic reactions [Time Frame: From Screening through Observational and Active Treatment (approximately 18 months)] Incidence of adverse events and serious adverse events [Time Frame: From screening through Observation and Active treatment (approximately 18 months)] Number of participants with clinically significant changes from baseline in vital signs [Time Frame: From Baseline through Observation and Active Treatment (approximately 18 months)] Incidence and severity of thromboticangiopathy [Time Frame: Throughout Active Treatment Phase (12 months)] Incidence of intravascular coagulation/consumption coagulopathy [Time Frame: Throughout Active Treatment Phase (12 months)]

Secondary Outcome

safety efficacy Incidence of joint bleeds [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Incidence of spontaneous bleeds [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Incidence of target joint bleeds [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Incidence of total bleeds (treated and untreated) [Time Frame: Through Observational and Active Treatment Phases (18 Months)] Change from baseline in the Hemophilia Joint Health Score (HJHS) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Change from baseline in (Haemophilia Adult Quality of Life Questionnaire (Haem-A-QoL) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Change from baseline in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Change from baseline in Hemophilia Adult Activities List (HAL) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Change from baseline in Hemophilia Pediatric Activities List (PedHAL) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Patient Global Impression of Change - Hemophilia (PGIC-H) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months] Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) [Time Frame: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months]

Key inclusion & exclusion criteria

Age minimum	>= 12age old
Age maximum	<= 74age old
Gender	Male
Include criteria	Inclusion Criteria * Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B with a minimum weight of 35 kg at screening. * Participant or legally authorized representative, or participant's caregiver capable of giving signed informed consent (or minor assent, when applicable). Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria: * No detectable or documented history of inhibitors * Participants on FVIII/FIX routine prophylaxis who have demonstrated at least 80% compliance with scheduled prophylaxis regimen during 6 months prior to enrollment and are willing to continue to receive routine prophylaxis treatment with FVIII/FIX replacement during the Observational Phase. * Participants with on-demand treatment regimen with >=6 acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 6 months period prior to enrollment and willing to continue to receive on demand treatment during the Observational Phase. 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 6 months prior to enrolment into the Observational Phase * Hemophilia A participants with on-demand treatment regimen with >=6 bleeding episodes or hemophilia B participants with >=4 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor during the 6 months prior to Enrollment into Observational Phase and willing to continue to receive on-demand treatment during the Observational Phase. * Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the 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 prior agreement from the Pfizer Medical Monitor * Participants who meet the bleeding criteria noted above and who are on routine prophylaxis (defined as treatment by IV injection of bypass factor to prevent bleeding) and have demonstrated at least 80% compliance with scheduled prophylaxis regimen during the 6 months prior to enrollment, may be considered for eligibility on a case-by-case basis with discussion and agreement from the Pfizer medical monitor.
Exclude criteria	Exclusion Criteria * Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease * Known planned surgical procedure during the planned study period. * Known hemostatic defect other than hemophilia A or B. * Abnormal renal or hepatic function * Current unstable liver or biliary disease * Abnormal hematologic parameters * Other acute or chronic medical or psychiatric condition or laboratory abnormality 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, * Current routine prophylaxis with bypassing agent or non-coagulation non-factor- replacement therapy, or any previous treatment with a gene therapy product for treatment of hemophilia (participants treated with prophylaxis using bypassing agents or who had prior treatment with non-factor products may be considered on a case-by-case basis). Regular, concomitant therapy with immunomodulatory drugs - Ongoing or planned use of immune tolerance induction during the Observational Phase or Active Treatment Phase, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention during the Active Treatment Phase * Previous exposure to PF 06741086 during participation in studies B7841002 and B7841003. * Participation in other studies involving investigational drug(s) or investigational vaccines within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry and/or during study participation. * CD4 cell count <=200/uL if human immunodeficiency virus (HIV)-positive * Screening ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. * Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention. * Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.