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): 188
• 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 Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology, Chinese Academy of Medical Sciences
• Croatia
  • Zagreb, Croatia, 10000
    • Klinicki bolnicki centar Zagreb
• France
  • Paris, France, 75015
    • Hôpital 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
    • Milan, Milan, Italy, 20122
      • Fondazione IRCCS Cà 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-ken
    • Nagoya, Aichi-ken, 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
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, 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
• Russia
  • Samara, Russia, 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
  • Niš, Serbia, 18000
    • Clinical Center Niš
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 05278
    • Kyung Hee University Hospital at Gangdong
• Spain
  • A Coruña, 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, Changhua County, Taiwan, 500
      • Changhua Christian Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Acibadem Adana Hospital
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Health Research and Practice Center Gazi Hospital
  • Antalya, Turkey (Türkiye), 07060
    • Akdeniz University Medical Faculty
  • Gaziantep, Turkey (Türkiye), 27310
    • Gaziantep University Sahinbey Research and Training Hospital
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul University Oncology Institute
  • Izmir, Turkey (Türkiye), 35040
    • Ege University Medical Faculty
  • Izmir, Turkey (Türkiye), 35210
    • Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes University Medical Faculty
  • Samsun, Turkey (Türkiye), 55280
    • Ondokuz Mayıs University Medical Faculty
  • Trabzon, Turkey (Türkiye), 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
Model-Based Annualized Bleeding Rate (ABR) of Treated Bleeding Events: Inhibitor Cohort (Participants With Prior OD Therapy at OP)	ABR is defined as number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If a participant did not complete a treatment period, days on treatment ended at last dosing date + 6 days. Treated bleed: If a bleed was treated with factor replacement or bypass agents within 48 hours of start of bleeding, regardless of the type of treatment (preventive, prophylaxis or OD medication). A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Model-Based ABR of Treated Bleeding Events: Non-Inhibitor Cohort (Participants With Prior OD Therapy at OP)	ABR is defined as number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If a participant did not complete a treatment period, days on treatment ended at last dosing date + 6 days. Treated bleed: If a bleed was treated with factor replacement or bypass agents within 48 hours of start of bleeding, regardless of the type of treatment (preventive, prophylaxis or OD medication). A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Model-Based ABR of Treated Bleeding Events: Non-Inhibitor Cohort (Participants With RP at OP)	ABR is defined as number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If a participant did not complete a treatment period, days on treatment ended at last dosing date + 6 days. Treated bleed: If a bleed was treated with factor replacement or bypass agents within 48 hours of start of bleeding, regardless of the type of treatment (preventive, prophylaxis or OD medication). A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Number of Participants With Adverse Events (AEs): Inhibitor and Non-Inhibitor Cohort	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious AEs and all other AEs.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Serious Adverse Events (SAEs): Inhibitor and Non-Inhibitor Cohort	AE: any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE: any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Thrombotic Events: Inhibitor and Non-Inhibitor Cohort	Thrombotic events are when a blood clot (thrombus) forms in a blood vessel in the arm, leg, lung, or head and can be life-threatening. A thrombus can occur in veins (venous thrombosis) or arteries (arterial thrombosis).	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Thrombotic Microangiopathy: Inhibitor and Non-Inhibitor Cohort	Thrombotic microangiopathy: pathological state where micro-vessels are occluded by platelet rich thrombi leading to thrombocytopenia (low platelets) and microangiopathic haemolytic anaemia (red blood cell destruction) and potential end organ damage.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Disseminated Intravascular Coagulation/ Consumption Coagulopathy: Inhibitor and Non-Inhibitor Cohort	Disseminated intravascular coagulation is characterized by widespread clotting in small blood vessels, and consumption of platelets and clotting factors by the clots, leading to bleeding.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF- 06741086: Inhibitor and Non-Inhibitor Cohort	ADA positive: A participant with >=1 treatment induced or treatment-boosted ADA response. NAb positive: An ADA positive participant with >=1 treatment induced or treatment boosted NAb response.	During prophylaxis treatment in ATP (12 months)
Number of Participants With Transient and Persistent ADA and NAb Against PF-06741086: Inhibitor and Non-Inhibitor Cohort	Persistent ADA: participant with treatment-induced or treatment-boosted ADA detected at 2 or more times during treatment including any follow-up, where first and last ADA positive samples separated by >=16 weeks. Transient ADA: treatment-induced or treatment-boosted ADA detected at only 1 time during treatment or follow-up. Persistent NAb: NAb-positive participant with first and last positive NAb samples detected >=16 weeks posttreatment, irrespective of any negative samples in between. Transient NAb: NAb-positive participant with (1) treatment-induced/treatment-boosted NAb sample detected at only 1 time posttreatment or (2) treatment-induced/treatment-boosted NAb samples detected at 2 or more times where first and last positive samples separated by <16 weeks, and participant's last sample was NAb or ADA negative.	During prophylaxis treatment in ATP (12 months)
Number of Participants With Injection Site Reactions (ISRs): Inhibitor and Non-Inhibitor Cohort	ISR included: injection site haematoma, injection site pain, injection site bruising, injection site erythema, injection site induration, injection site oedema, Injection site pruritus and Injection site swelling. ISR graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 where grade 1: tenderness with or without associated symptoms (warmth, erythema, itching), grade 2: pain, lipodystrophy, edema, phlebitis, grade 3: ulceration or necrosis, severe tissue damage, operative intervention indicated, grade 4: life-threatening consequences, urgent intervention indicated and grade 5: death. In this outcome measure only categories with non-zero values reported.	During prophylaxis treatment in ATP (12 months)
Number of Participants With Clinically Significant Changes in Physical Examinations: Inhibitor and Non-Inhibitor Cohort	Physical examination included assessments of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Height and weight were also measured and recorded. Clinical significance in physical examinations was determined by investigator.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Clinically Significant Changes in Vital Signs: Inhibitor and Non-Inhibitor Cohort	Vital signs included temperature, pulse rate, respiratory rate, and blood pressure. Blood pressure and pulse rate were measured in a supine position using completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Respiratory rate was measured by observing and counting the respirations of the participant for 30 seconds and multiplied by 2. Clinical significance of vital signs was determined by investigator.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters: Inhibitor and Non-Inhibitor Cohort	Hematology included: hemoglobin; leukocytes; neutrophils; and platelets. Chemistry included: potassium; aspartate aminotransferase; creatinine; alkaline phosphatase; total bilirubin; albumin; calcium corrected, estimated decreased; sodium; and calcium. Clinical significance of laboratory parameters was determined by investigator.	OP reporting group: Up to 6 months; ATP reporting group: up to 13 months (includes 28-35 days of safety follow-up post last dose of study drug)
Number of Participants With Severe/ Systematic Hypersensitivity and Anaphylactic Reactions: Inhibitor and Non-Inhibitor Cohort	Systemic hypersensitivity is a complex immune response where the immune system reacts excessively to an antigen, often leading to severe allergic reactions, including widespread symptoms (which may affect multiple organs), such as rash, swelling of your face, lips, mouth, or tongue, trouble breathing, wheezing, dizziness, fainting, fast heartbeat, pounding in your chest or sweating. Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy causing substance.	During prophylaxis treatment in ATP (12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model-Based ABR of Joint Bleeds: Inhibitor and Non-Inhibitor Cohort	ABR: number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If a participant did not complete a treatment period, days on treatment ended at last dosing date + 6 days. Joint bleed: bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of the following: pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Model-Based ABR of Spontaneous Bleeds: Inhibitor and Non-Inhibitor Cohort	ABR: number of bleeding episodes per year. ABR was calculated as the number of bleeds requiring treatments/ (days on treatment period/365.25). If a participant did not complete a treatment period, the days on treatment ended at the last dosing date + 6 days. Spontaneous bleed: Bleeding for no apparent/known reason particularly into the joints, muscles, and soft tissues. A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Model-Based ABR of Target Joint Bleeds: Inhibitor and Non-Inhibitor Cohort	ABR: number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If participant did not complete a treatment period, days on treatment ended at last dosing date + 6 days. Target joint: a major joint into which repeated bleeds occurred. Joint bleed: bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of following: pain or unusual sensation in joint, palpable swelling, and warmth of the skin over joint. A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Model-Based ABR of Total Bleeds: Inhibitor and Non-Inhibitor Cohort	ABR: number of bleeding episodes per year. ABR was calculated as number of bleeds requiring treatments/ (days on treatment period/365.25). If participant did not complete treatment period, days on treatment ended at last dosing date + 6 days. Treated bleed: If a bleed was treated with factor replacement or bypass agents within 48 hours of start of bleeding, regardless of the type of treatment (preventive, prophylaxis or on-demand medication). Untreated bleed: If a bleed was untreated with factor replacement or bypass agents within 48 hours of start of bleeding, regardless of the type of treatment (preventive, prophylaxis or on-demand medication), it was considered as an untreated bleed. Total bleeds: Treated bleeds + untreated bleeds. A model-based ABR using a repeated measures negative binomial model is reported for this outcome measure.	OP reporting group: Up to 6 months; ATP reporting group: up to 12 months
Change From Baseline in Hemophilia Joint Health Score (HJHS) at Month 6: Non-Inhibitor Cohort	HJHS evaluated total joint score for 6 joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) and the global gait score. Joint total score per joint ranged from 0 to 20 (evaluated as: swelling [0-3], duration of swelling [0-1], muscle atrophy [0-2], crepitus on motion [0-2], flexion loss [0-3], extension loss [0-3], joint pain [0-2], and strength [0-4]). Global gait score ranged from 0 to 4 based on walking, stairs, running, and hopping on 1 leg. HJHS total score was sum of total joint score for 6 joints (0 to 120) and global gait score (0 to 4). The total HJHS score ranged from 0 to 124, where higher scores indicated worse joint health.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in HJHS at Month 6: Inhibitor Cohort	HJHS evaluated total joint score for 6 joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) and the global gait score. Joint total score per joint ranged from 0 to 20 (evaluated as: swelling [0-3], duration of swelling [0-1], muscle atrophy [0-2], crepitus on motion [0-2], flexion loss [0-3], extension loss [0-3], joint pain [0-2], and strength [0-4]). Global gait score ranged from 0 to 4 based on walking, stairs, running, and hopping on 1 leg. HJHS total score was sum of total joint score for 6 joints (0 to 120) and global gait score (0 to 4). The total HJHS score ranged from 0 to 124, where higher scores indicated worse joint health.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) Total Score and Physical Health Domain at Month 6: Non-Inhibitor Cohort, Participants >=17 Years	Haem-A-QoL assessed health-related quality of life (QoL) in adult participants (>=17 years of age) with hemophilia. It contained 46 items with 10 domains that assessed health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with haemophilia; treatment; future; family planning; partnership and sexuality. All items were based on a 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring was performed by averaging non-missing item responses for each domain, then each domain score was rescaled from 0 to 100, lower scores signified higher QoL. Total Haem-A-QoL score was averaged across the 46 items values and then rescaled from 0 to 100, lower Haem-A-QoL scores signified better QoL.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Haem-A-QoL Total Score and Physical Health Domain at Month 6: Inhibitor Cohort, Participants >=17 Years	Haem-A-QoL assessed health-related quality of life (QoL) in adult participants (>=17 years of age) with hemophilia. It contained 46 items with 10 domains that assessed health in the following areas: physical health; feelings; view of self; sports and leisure; work and school; dealing with haemophilia; treatment; future; family planning; partnership and sexuality. All items were based on a 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring was performed by averaging non-missing item responses for each domain, then each domain score was rescaled from 0 to 100, lower scores signified higher QoL. Total Haem-A-QoL score was averaged across the 46 items values and then rescaled from 0 to 100, lower Haem-A-QoL scores signified better QoL.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Hemophilia Quality of Life Questionnaire for Children (Haemo-QoL) Total Score at Month 6: Non-Inhibitor Cohort, Participants 12 to <17 Years	Haemo-QoL assessed health-related QoL in adolescent participants (12 to <17 years of age) with hemophilia. It contains 12 items with 77 domains that assesses health in the following areas: physical health; feelings; attitude/view; family; friends; other people; sport and school; coping/dealing; treatment; perceived support; future and relationship. All items were based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring was performed by averaging non-missing item responses for each domain, then rescaled from 0 to 100, lower scores signified higher QoL. Total Haem-A QoL score was averaged across the 77 items values and then rescaled from 0 to 100, lower Haemo-QoL scores signified better QoL.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Haemo-QoL Total Score at Month 6: Inhibitor Cohort, Participants 12 to <17 Years	Haemo-QoL assessed health-related QoL in adolescent participants (12 to <17 years of age) with hemophilia. It contains 12 items with 77 domains that assesses health in the following areas: physical health; feelings; attitude/view; family; friends; other people; sport and school; coping/dealing; treatment; perceived support; future and relationship. All items were based on 5-point Likert type scale (1= never, 2= rarely, 3= sometimes, 4= often, 5= all the time). Scoring was performed by averaging non-missing item responses for each domain, then rescaled from 0 to 100, lower scores signified higher QoL. Total Haem-A QoL score was averaged across the 77 items values and then rescaled from 0 to 100, lower Haemo-QoL scores signified better QoL.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Hemophilia Activities List (HAL) Total Score at Month 6: Non-Inhibitor Cohort, Participants >=17 Years	The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults (>=17 years of age). The 7 domains of this instrument contained 42 items in total, as follows: lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was sum of all items and scored 42 to 252, which were transformed to 0 - 100, where higher scores indicated better functional status.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in HAL Total Score at Month 6: Inhibitor Cohort, Participants >=17 Years	The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults (>=17 years of age). The 7 domains of this instrument contained 42 items in total, as follows: lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. HAL total score was sum of all items and scored 42 to 252, which were transformed to 0 - 100, where higher scores indicated better functional status.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in Pediatric Hemophilia Activities List (pedHAL) Total Score at Month 6: Non-Inhibitor Cohort, Participants 12 to <17 Years	The pedHAL was a multiple domain measure of the impact of hemophilia on functional abilities in adolescents (12 to <17 years of age). The 7 domains of this instrument contained 53 items in total, as follows: sitting/kneeling/standing; functions of the legs; functions of the arms; use of transportation; self-care; household tasks; leisure activities and sports. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. pedHAL total score was normalized in a range of 0 - 100, where higher scores indicated better functional status.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in pedHAL Total Score at Month 6: Inhibitor Cohort, Participants 12 to <17 Years	The pedHAL was a multiple domain measure of the impact of hemophilia on functional abilities in adolescents (12 to <17 years of age). The 7 domains of this instrument contained 53 items in total, as follows: sitting/kneeling/standing; functions of the legs; functions of the arms; use of transportation; self-care; household tasks; leisure activities and sports. Items were rated on 6-point scale 1 (impossible) to 6 (never) that described difficulty due to hemophilia. pedHAL total score was normalized in a range of 0 - 100, where higher scores indicated better functional status.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Patient Global Impression of Change-Hemophilia (PGIC-H) at Month 6: Non-Inhibitor Cohort	The PGIC-H was a single item assessment of the participant's overall impression of change in their life with hemophilia, on a 7-point scale (1= greatly improved to 7= greatly worsened, where lower scores indicated better improvement).	Month 6
PGIC-H at Month 6: Inhibitor Cohort	The PGIC-H was a single item assessment of the participant's overall impression of change in their life with hemophilia, on a 7-point scale (1= greatly improved to 7= greatly worsened, where lower scores indicated better improvement).	Month 6
Change From Baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Index and VAS Scores at Month 6: Non-Inhibitor Cohort	EQ-5D-5L consisted of participant completed questionnaire with 2 components: health state profile index and visual analogue scale (VAS). EQ-5D health state profile index has 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), with 5 levels (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extreme problems). Responses to 5 dimensions comprised health state index value. E.g. if a participant responds "no problems" for each 5 dimensions, then health state was coded as "11111" with predefined index value to it. EQ-5D-5L index score ranged from -0.594 to 1, United Kingdom look-up value was applied to all participants, higher scores indicated better health states. The EQ- VAS measured participant's self-rated health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by VAS, where higher scores indicated better heath states.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6
Change From Baseline in EQ-5D-5L Index and VAS Scores at Month 6: Inhibitor Cohort	EQ-5D-5L consisted of participant completed questionnaire with 2 components: health state profile index and visual analogue scale (VAS). EQ-5D health state profile index has 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), with 5 levels (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extreme problems). Responses to 5 dimensions comprised health state index value. E.g. if a participant responds "no problems" for each 5 dimensions, then health state was coded as "11111" with predefined index value to it. EQ-5D-5L index score ranged from -0.594 to 1, United Kingdom look-up value was applied to all participants, higher scores indicated better health states. The EQ- VAS measured participant's self-rated health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by VAS, where higher scores indicated better heath states.	OP reporting group: Baseline (Day 1, day of study enrollment), Month 6; ATP reporting group: Baseline (before dose on Day 1 of ATP), Month 6

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Matino D, Acharya SS, Taylor CT, Sun P, Agathon D, Raje S, Gould T, Palladino A, Mahlangu J, Lissitchkov T, Todorova M, Chan A, Carcao M, Sun J, Yang R, Wu R, Jin C, Zeng X, Boban A, Bilic E, Frenzel L, Fung Chan GC, Kong Li C, Apte S, Choraria N, Chistolini A, Marchesini E, Peyvandi F, Fujii T, Matsushita T, Kaneda M, Lyu CJ, Park YS, Kim S, Martinez LV, Adrian JM, Wali Y, Al Khabori M, Kurtov I, Alzahrani H, Zaher G, Micic D, Miljic P, Kostic G, Vucic M, Djurdjevic P, Hidalgo OB, Porras JG, Jimenez-Yuste V, Calvo Villas JM, Lopez Fernandez MF, Albayrak C, Okan V, Balkan C, Sahin F, Antmen A, Unal E, Visweshwar N, Sharathkumar A, Kruse-Jarres R. Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial. Blood. 2026 Feb 26;147(9):920-931. doi: 10.1182/blood.2025031065.
• Matino D, Palladino A, Taylor CT, Hwang E, Raje S, Nayak S, McDonald R, Acharya SS, Mahlangu J, Jimenez-Yuste V, Choraria N, Yang R, Li CK, Al-Khabori M, Wali Y, Morales Adrian J, Park YS, Zulfikar OB, Teeter J. Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial. Blood. 2025 Oct 2;146(14):1654-1663. doi: 10.1182/blood.2024027468.

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): August 14, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

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: Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemophilia A; Hemorrhage; Hemophilia B; marstacimab
• 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