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

NCT03938792 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: B78410052018-003660-31
• Study Type: interventional
• Target: 189
• Locations: 20 countries
• Sites: 62

Brief Summary

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.

Conditions

Hemophilia A; Hemophilia B

Keywords

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

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (11)

• 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

Study Arms (1)

PF-06741086

EXPERIMENTAL

Participants will be assigned to treatment with PF-06741086 after a 6 month Observation Phase on their current hemophilia regimen.

Drug: PF-06741086

Interventions

PF-06741086 DRUG

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.

PF-06741086

Eligibility Criteria

• Age: 12 Years - 74 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (62)

USF Health Morsani Center For Advanced Healthcare

Tampa, Florida, 33612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Northwell Health HTC

New Hyde Park, New York, 11040, United States

Location

Washington Institute for Coagulation

Seattle, Washington, 98101, United States

Location

National Specialized Hospital for the Active Treatment of Hematological Diseases - EAD, Sofia

Sofia, 1756, Bulgaria

Location

UMHAT "Prof.Dr. Stoyan Kirkovich"

Stara Zagora, 6003, Bulgaria

Location

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8S 4K1, Canada

Location

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

The Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550004, China

Location

Jiangxi Provincial People's Hospital

Nanchang, Jiangxi, 306113, China

Location

Institute of Hematology, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

Beijing Children's Hospital, Capital Medical University

Beijing, 100045, China

Location

Klinicki bolnicki centar Zagreb

Zagreb, 10000, Croatia

Location

Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Nirmal Hospital Pvt, Ltd

Surat, Gujarat, 395002, India

Location

Sahyadri Clinical Research and Development Center

Pune, Maharashtra, 411004, India

Location

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411004, India

Location

Christian Medical College

Vellore, Tamil Nadu, 632004, India

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Milan, 20122, Italy

Location

Università degli Studi di Perugia, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della

Perugia, PERUGIA, 06156, Italy

Location

Università degli Studi di Roma "Sapienza"-Policlinico Umberto I

Roma, RM, 00161, Italy

Location

Nagoya University Hospital - Transfusion Medicine

Nagoya, Aichi-ken, 466-8560, Japan

Location

Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551, Japan

Location

Sapporo Tokushukai Hospital

Sapporo, Hokkaido, 004-0041, Japan

Location

Saitama Medical University Hospital

Iruma-gun, Saitama, 350-0495, Japan

Location

Hospital Universitario "Dr Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 64460, Mexico

Location

Centro Multidisciplinario para el Desarrollo Especializado de la Inv. Clínica en Yucatán, S.C.P.

Mérida, Yucatán, 97130, Mexico

Location

Sultan Qaboos University Hospital

Muscat, 123, Oman

Location

FGBOU VO "Samara State Medical University" of MoH of Russia

Samara, 443079, Russia

Location

King Abdulaziz University Hospital

Jeddah, 21589, Saudi Arabia

Location

King Faisal Specialist Hospital & Research Center

Riyadh, Saudi Arabia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute for Mother and Child healthcare "Dr Vukan Cupic"

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center Nis

Niš, 18000, Serbia

Location

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, 2193, South Africa

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Kyung Hee University Hospital At Gangdong

Seoul, 05278, South Korea

Location

Hospital Universitario A Coruna

A Coruña, A CORUNA, 15006, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, BARCELONA, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca

Salamanca, SALAMANCA, 37007, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, ZARAGOZA, 50009, Spain

Location

ChangHua Christian Hospital

Changhua, CHANGHUA COUNTY, 500, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Acibadem Adana Hospital

Adana, 01130, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06230, Turkey (Türkiye)

Location

Gazi University Health Research and Practice Center Gazi Hospital

Ankara, 06500, Turkey (Türkiye)

Location

Akdeniz University Medical Faculty

Antalya, 07060, Turkey (Türkiye)

Location

Gaziantep University Sahinbey Research and Training Hospital

Gaziantep, 27310, Turkey (Türkiye)

Location

Istanbul University Oncology Institute

Istanbul, 34093, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35040, Turkey (Türkiye)

Location

Dr. Behcet Uz Child Diseases Surgery Education and Research Hospital

Izmir, 35210, Turkey (Türkiye)

Location

Erciyes University Medical Faculty

Kayseri, 38039, Turkey (Türkiye)

Location

Ondokuz Mayıs University Medical Faculty

Samsun, 55280, Turkey (Türkiye)

Location

Karadeniz Technical University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

Related Publications (2)

• Matino D, Acharya S, Taylor CT, Sun P, Agathon D, Raje S, Gould T, Palladino A, Mahlangu J. Efficacy and Safety of Marstacimab Prophylaxis in Hemophilia A/B With Inhibitors: Results from the Phase 3 BASIS Trial. Blood. 2025 Dec 6:blood.2025031065. doi: 10.1182/blood.2025031065. Online ahead of print.

  PMID: 41351884 DERIVED

• 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.

  PMID: 40608864 DERIVED

Related Links

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

MeSH Terms

Conditions

Hemophilia A; Hemophilia B; Hemorrhage

Interventions

marstacimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a one way Cross-Over Prevention study with 1 Arm that has No masking.

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 6, 2019
• Study Start: March 9, 2020
• Primary Completion: April 29, 2025
• Study Completion: April 29, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (4); BU (2); FR (1); ES (5); HK (2); TW (2); IN (4); SA (2); KR (3); ME (2); IT (3); TU (11); ZA (1); CR (1); CN (5); JP (4); RU (1); CA (4); OM (1); SE (4)