Study of the Efficacy and Safety PF-06741086 in Adult and Teenage Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B
Hemophilia A, Hemophilia B
About this trial
This is an interventional treatment trial for Hemophilia A focused on measuring Factor VIII, Factor IX, Inhibitors, Anti-Tissue Factor Pathway Inhibitor (TFPI), Subcutaneous (sc), Prophylaxis, On-Demand, BASIS, Inhibitor, SC, Subcutaneous, Injection, On demand, aTFPI, Anti-TFPI, Severe hemophilia, Severe bleeding, Hemophilia, PF-06741086, PF 06741086, Marstacimab
Eligibility 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.
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.
Sites / Locations
- USF Health Morsani Center For Advanced Healthcare
- University of IowaRecruiting
- Northwell Health HTCRecruiting
- Washington Institute for CoagulationRecruiting
- National Specialized Hospital for the Active Treatment of Hematological Diseases - EAD, Sofia
- UMHAT "Prof.Dr. Stoyan Kirkovich"
- McMaster Children's HospitalRecruiting
- McMaster University Medical Centre - Hamilton Health Sciences
- McMaster Children's Hospital
- McMaster University
- The Hospital For Sick Children
- Nanfang Hospital, Southern Medical University
- The Affiliated Hospital of Guizhou Medical UniversityRecruiting
- Jiangxi Provincial People's Hospital
- Institute of Hematology, Chinese Academy of Medical SciencesRecruiting
- Beijing Children's Hospital, Capital Medical UniversityRecruiting
- Klinicki bolnicki centar Zagreb
- Klinicki bolnicki centar ZagrebRecruiting
- Hôpital Necker Enfants Malades
- Prince of Wales Hospital
- Queen Mary Hospital
- Nirmal Hospital Pvt, LtdRecruiting
- Sahyadri Clinical Research and Development CenterRecruiting
- Sahyadri Super Speciality HospitalRecruiting
- Christian Medical College
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
- Università degli Studi di Roma "Sapienza"-Policlinico Umberto I
- Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della
- Nagoya University Hospital - Transfusion MedicineRecruiting
- Sapporo Tokushukai HospitalRecruiting
- Saitama Medical University HospitalRecruiting
- Tokyo Metropolitan Children's Medical Center
- Ogikubo Hospital
- Hiroshima University HospitalRecruiting
- Kyungpook National University Hospital
- Severance Hospital, Yonsei University Health SystemRecruiting
- Kyung Hee University Hospital At Gangdong
- Hospital Universitario "Dr Jose Eleuterio Gonzalez"
- Centro Multidisciplinario para el Desarrollo Especializado de la Inv. Clínica en Yucatán, S.C.P.Recruiting
- Sultan Qaboos University Hospital
- FGBOU VO "Samara State Medical University" of MoH of Russia
- King Abdulaziz University Hospital
- King Faisal Specialist Hospital & Research CenterRecruiting
- Clinical Center of Serbia
- Institute for Mother and Child healthcare "Dr Vukan Cupic"
- Clinical Center Kragujevac
- Clinical Center Nis
- Charlotte Maxeke Johannesburg Academic HospitalRecruiting
- Hospital Universitario A Coruna
- Hospital Universitario Vall d´Hebron
- Hospital Universitario La Paz
- Hospital Universitario de Salamanca
- Hospital Universitario Miguel Servet
- ChangHua Christian Hospital
- Taichung Veterans General Hospital
- Acibadem Adana HospitalRecruiting
- Hacettepe University Medical FacultyRecruiting
- Hacettepe University Medical Faculty
- Gazi University Health Research and Practice Center Gazi HospitalRecruiting
- Akdeniz University Medical Faculty
- Gaziantep University Sahinbey Research and Training Hospital
- Istanbul University Oncology InstituteRecruiting
- Ege University Medical Faculty
- Ege University Medical FacultyRecruiting
- Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital
- Erciyes University Medical Faculty
- Ondokuz Mayıs University Medical FacultyRecruiting
- Karadeniz Technical University Medical Faculty
Arms of the Study
Arm 1
Experimental
PF-06741086
Participants will be assigned to treatment with PF-06741086 after a 6 month Observation Phase on their current hemophilia regimen.