Health Condition 1: D67- Hereditary factor IX deficiency Health Condition 2: D66- Hereditary factor VIII deficiency
Conditions
Interventions
Intervention1: PF-06741086 (marstacimab
anti-TFPI): 300 milligrams(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 Intervention
Sponsors
Pfizer Inc
Eligibility
Inclusion criteria
Inclusion criteria: (1) Participants with a diagnosis of severe hemophilia A or B (2) Participant or legally authorized representative or participants caregiver capable of giving signed informed consent (or minor assent, when applicable) (3) Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria: (a) No detectable or documented history of inhibitors. (b) Participants outside the US and Canada with FVIII/FIX replacement, and willing to continue to receive routine prophylaxis treatment with FVIII/FIX replacement during the Observational Phase. Participants in the US and Canada receiving routine prophylaxis treatment not eligible to be enrolled. (c) Participants with on-demand treatment regimen with >=6 acute bleeding episodes (spontaneous and/or traumatic) that required coagulation factor infusion during the 6 months period prior to Screening and willing to continue to receive on demand treatment during the Observational Phase. (d) 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 approval from the Pfizer Medical Monitor. (4) Participants who are enrolled into the Inhibitor Cohort must also meet the following criteria: (a) Documentation of current high titer inhibitor (>=5 BU/mL) or current low titer inhibitor ( (b) Participants with on-demand treatment regimen with >=6 bleeding episodes (spontaneous and/or traumatic) necessitating treatment with bypass factor for at least 6 months prior to screening and willing to continue to receive on-demand treatment during the Observational Phase.
Exclusion criteria
Exclusion criteria: (1) Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease (2) Known planned surgical procedure during the planned study period (3) Known hemostatic defect other than hemophilia A or B (4) Abnormal renal or hepatic function (5) Current unstable liver or biliary disease (6) Abnormal hematologic parameters (7) Abnormal coagulation activity (8) 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 (9) Current routine prophylaxis with bypassing agent or non-coagulation non-factor- replacement therapy (10) Regular, concomitant therapy with immunomodulatory drugs (11) Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the Active Treatment Phase (12) Previous exposure to PF 06741086 during to participation in studies B7841002 and B7841003 (13) Participation in other studies involving investigational drug(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry and/or during study participation (14) CD4 cell count (15) Clinically relevant ECG abnormalities that may affect participant safety or interpretation of study results (16) Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention (17) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Annualized bleeding rate (ABR) of treated bleeding events Derived for each subject for each treatment period 2.Incidence and severity of thrombotic events 3.Incidence of anti drug antibody [ADA] against PF-06741086 4.Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086 5.Incidence and severity of injection site reaction 6.Number of participants with clinically significant changes from baseline in physical examTimepoint: 1.Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months 2.Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months 3.Throughout Active Treatment Phase (12 months) 4.Throughout Active Treatment Phase (12 months) 5.Throughout Active Treatment Phase (12 months) 6.From Baseline through Observation and Active Treatment (approximately 18 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in (Haemophilia Adult Quality of Life Questionnaire (Haem-A-QoL)Timepoint: 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)Timepoint: 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)Timepoint: 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)Timepoint: 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)Timepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Change from baseline in the Hemophilia Joint Health Score (HJHS)Timepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Incidence of joint bleedsTimepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Incidence of spontaneous bleedsTimepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Incidence of target joint bleedsTimepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Incidence of total bleeds (treated and untreated)Timepoint: Through Observational and Active Treatment Phases (18 Months);Patient Global Impression of Change - Hemophilia (PGIC-H)Timepoint: Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months;Percentage of participants with no bleed | — |
Countries
Australia, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, France, Germany, Hong Kong, India, Ireland, Italy, Japan, Mexico, Oman, Republic of Korea, Russian Federation, Saudi Arabia, Serbia, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Seema Pai
Pfizer Limited
Outcome results
None listed