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

An Open-Label Study in Adolescent and Adult Severe (Coagulation Factor Activity <1%) Hemophilia A Participants With or Without Inhibitors or Moderately Severe to Severe Hemophilia B Participants (Coagulation Factor Activity ≤2%) With or Without Inhibitors Comparing Standard Treatment to PF-06741086 Prophylaxis

Treatment with PF-06741086 is anticipated to demonstrate a clinically relevant advantage and/or a major contribution to patient care in comparison to current methods of treatment for hemophilia A or B because it works differently than factor replacement products and will work in the presence of inhibitors. The potential for once weekly (QW) subcutaneous (SC) administration provides for treatment options in the absence of reliable vascular access, increased convenience and may enable better compliance. Combined, these qualities should result in a reduction of bleeding episodes.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Drug: PF-06741086

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1756
    • National Specialized Hospital for the Active Treatment of Hematological Diseases - EAD, Sofia
  • Stara Zagora, Bulgaria, 6003
    • UMHAT "Prof.Dr. Stoyan Kirkovich"
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster Children's Hospital
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre - Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• China
  • Beijing, China, 100045
    • Beijing Children's Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • The Affiliated Hospital of Guizhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 306113
      • Jiangxi Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology, Chinese Academy of Medical Sciences
• Croatia
  • Zagreb, Croatia, 10000
    • Klinicki bolnicki centar Zagreb
• France
  • Paris, France, 75015
    • Hopital Necker Enfants Malades
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• India
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital Pvt, Ltd
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Clinical Research And Development Center
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College
• Italy
  • Perugia, Italy, 06156
    • Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della
  • Milan
    • Milano, Milan, Italy, 20122
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • RM
    • Roma, RM, Italy, 00161
      • Università degli Studi di Roma "Sapienza"-Policlinico Umberto I
• Japan
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital - Transfusion Medicine
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 004-0041
      • Sapporo Tokushukai Hospital
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05278
    • Kyung Hee University Hospital at Gangdong
• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario "Dr Jose Eleuterio Gonzalez"
  • Yucatán
    • Mérida, Yucatán, Mexico, 97130
      • Centro Multidisciplinario para el Desarrollo Especializado de la Inv. Clínica en Yucatán, S.C.P.
• Oman
  • Muscat, Oman, 123
    • Sultan Qaboos University Hospital
• Russian Federation
  • Samara, Russian Federation, 443079
    • FGBOU VO "Samara State Medical University" of MoH of Russia
• Saudi Arabia
  • Jeddah, Saudi Arabia, 21589
    • King AbdulAziz University Hospital
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital & Research Center
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Institute for Mother and Child healthcare "Dr Vukan Cupic"
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Nis, Serbia, 18000
    • Clinical Center Nis
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• Spain
  • A Coruna, Spain, 15006
    • Hospital Universitario A Coruna
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d´Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Changhua County
    • Changhua City, Changhua County, Taiwan, 500
      • Changhua Christian Hospital
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hospital
  • Ankara, Turkey, 06230
    • Hacettepe University Medical Faculty
  • Ankara, Turkey, 06500
    • Gazi University Health Research and Practice Center Gazi Hospital
  • Antalya, Turkey, 07060
    • Akdeniz University Medical Faculty
  • Gaziantep, Turkey, 27310
    • Gaziantep University Sahinbey Research and Training Hospital
  • Istanbul, Turkey, 34093
    • Istanbul University Oncology Institute
  • Izmir, Turkey, 35040
    • Ege University Medical Faculty
  • Izmir, Turkey, 35210
    • Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital
  • Kayseri, Turkey, 38039
    • Erciyes University Medical Faculty
  • Samsun, Turkey, 55280
    • Ondokuz Mayıs University Medical Faculty
  • Trabzon, Turkey, 61080
    • Karadeniz Technical University Medical Faculty
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • USF Health Morsani Center For Advanced Healthcare
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • New York
    • New Hyde Park, New York, United States, 11040
      • Northwell Health HTC
  • Washington
    • Seattle, Washington, United States, 98101
      • Washington Institute for Coagulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 74 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06741086; Participants will be assigned to treatment with PF-06741086 after a 6 month Observation Phase on their current hemophilia regimen.	Drug: PF-06741086; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized bleeding rate (ABR) of treated bleeding events	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)	Through Observational Phase (6months) and Active Treatment Phase (12 months) for total of approximately 18 months
Incidence and severity of thrombotic events		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		Throughout Active Treatment Phase (12 months)
Incidence of clinically significant persistent neutralizing antibody [NAb] against PF-06741086		Throughout Active Treatment Phase (12 months)
Incidence and severity of injection site reaction		Throughout Active Treatment Phase (12 months)
Number of participants with clinically significant changes from baseline in physical exam		From Baseline through Observation and Active Treatment (approximately 18 months)
Incidence of clinically significant laboratory value abnormalities		From Screening through Observation and Active Treatment (approximately 18 months)
Incidence of severe hypersensitivity and anaphylactic reactions		From Screening through Observational and Active Treatment (approximately 18 months)
Incidence of adverse events and serious adverse events		From screening through Observation and Active treatment (approximately 18 months)
Number of participants with clinically significant changes from baseline in vital signs		From Baseline through Observation and Active Treatment (approximately 18 months)
Incidence and severity of thromboticangiopathy		Throughout Active Treatment Phase (12 months)
Incidence of intravascular coagulation/consumption coagulopathy		Throughout Active Treatment Phase (12 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of joint bleeds	Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Incidence of spontaneous bleeds	Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Incidence of target joint bleeds	Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months
Incidence of total bleeds (treated and untreated)	Through Observational and Active Treatment Phases (18 Months)
Change from baseline in the Hemophilia Joint Health Score (HJHS)	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)	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)	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)	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)	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)	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)	Through Observational Phase (6 months) and Active Treatment Phase (12 months) for total of approximately 18 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2020
• Primary Completion (Actual): April 29, 2025
• Study Completion (Actual): April 29, 2025

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Subcutaneous; Prophylaxis; On-Demand; Factor VIII; Hemophilia; Injection; Factor IX; Inhibitors; Inhibitor; PF-06741086; Marstacimab; Anti-TFPI; SC; Anti-Tissue Factor Pathway Inhibitor (TFPI); Subcutaneous (sc); On demand; aTFPI; Severe hemophilia; Severe bleeding; BASIS; PF 06741086
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: B7841005; 2018-003660-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No