Clinical trial NCT05611801: A Clinical Trial of Study Medicine (Marstacimab) in Pediatric Patients With Hemophilia A or Hemophilia B
Official title: AN OPEN-LABEL STUDY IN PEDIATRIC (<18 YEARS OF AGE), SEVERE HEMOPHILIA A PARTICIPANTS (COAGULATION FACTOR ACTIVITY <1%) WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY =2%) WITH OR WITHOUT INHIBITORS COMPARING 12 MONTHS OF HISTORICAL STANDARD TREATMENT TO MARSTACIMAB PROPHYLAXIS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemophilia A
Hemophilia B
Keywords: Factor VIII Inhibitor
Factor IX Inhibitor
PF-06741086
Marstacimab
Anti-TFPI
Factor VIII
Factor IX
Inhibitors
Anti-Tissue Factor Pathway Inhibitor (TFPI)
Subcutaneous (sc)
Prophylaxis
On-Demand
BASIS KIDS
Inhibitor
SC
Subcutaneous
Injection
On demand
aTFPI
Severe hemophilia
Severe bleeding
Hemophilia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-11-10
Enrollment: 100
Sex: MALE
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called marstacimab) for the potential treatment of hemophilia in pediatric patients.

This study will enroll pediatric participants from ages 1 to 17 years in a sequential manner. The study will open enrollment to adolescent participants aged 12 to 17 years first. Then children aged 6 to 11 years will be permitted to enroll. Lastly, children aged 1 to 5 years will be permitted to enroll.

This study will enroll participants who:

* have severe Hemophilia A or moderately severe to severe Hemophilia B (with or without inhibitors)
* have accurate historical records documenting all factor VIII, factor IX, or bypass agent infusions and hemophilia bleed events for at least 1 year prior to entering the study
* if a non-inhibitor patient, must be on a stable routine prophylaxis regimen with factor VIII or factor IX replacement products for at least 12 months prior to study entry
* if an inhibitor patient, must be on an on-demand bypass treatment regimen during the 12 months prior to study entry

All participants in this study will receive marstacimab to use prophylactically. Marstacimab will be given once a week as a subcutaneous (under the skin) shot. The first dose of marstacimab will be given at the study site by the study site staff. During the 12-month treatment period, weekly doses of marstacimab can be given at home, or if preferred, the doses may be given by the study site staff.

To help us determine if the study medicine is safe and effective, we will compare participant experiences when they are taking the study medicine to a historical period when they were not. Researchers want to see if the study medicine works to prevent the bleeding episodes commonly experienced by patients with Hemophilia.

Participants will be in this study for about 14 months (approximately 1 month in a Screening period, 12 months receiving treatment, and 1 month in a follow-up period) during which they will visit the study site at least 10 times. If preferred, and if local regulations allow it, 2 of the study visits can be completed at the participant's home instead of at the study site. There will also be 6 scheduled telephone calls approximately every 2 months.


Eligibility criteria: Inclusion Criteria:

* Male participants of appropriate age and required minimum weight
* Participants aged 12 to 17 years must be at least 25 kgs at time of consent.
* Participants aged 6 to 11 years must be at least 19 kgs at time of consent.
* Minimum weight requirement for participants aged 1 to 5 years is to be determined.
* Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B
* Participants must have at least 1 year of diary and/or medical records available in which exogenous FVIII or FIX replacement or bypass agent infusions and hemophilic bleeding episodes were consistently documented over the 12 months prior to the time of consent.

Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:

* No current detectable inhibitor and no documented history of inhibitors in the 5 years prior to consent
* Must have at least 50 exposure days to FVIII/FIX replacement products
* Must be at least 80% compliant with a stable and effective routine prophylaxis regimen with FVIII/FIX replacement products, for at least 12 months prior to consent

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 12 months prior to the time of consent
* Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the high 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 discussion and agreement from the Pfizer medical monitor.
* Hemophilia A participants with on-demand treatment regimen with ≥12 bleeding episodes or hemophilia B participants with on-demand treatment regimen with ≥8 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor in the 12 months prior to informed consent
* Participants must be on an on-demand bypass treatment regimen during the 12 months prior to informed consent

Exclusion Criteria:

* Known coronary artery, thrombotic, or ischemic disease, or current evidence of congenital or acquired thrombophilic disease such as Anti-thrombin III deficiency, Factor V Leiden mutation, prothrombin 20210 mutation, protein C deficiency, protein S deficiency and antiphospholipid syndrome.
* Known planned surgical procedure during the planned study period
* Known hemostatic defect other than hemophilia A or B
* Abnormal hematology, renal or hepatic function laboratory results at screening
* Other acute or chronic medical or psychiatric condition 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
* Individuals with known allergic reaction or hypersensitivity to hamster protein or other components of the study intervention
* Current routine prophylaxis with bypassing agent, non-coagulation non-factor replacement therapy (eg, emicizumab), or any previous treatment with a gene therapy product for treatment of hemophilia
* Participants with inhibitors who are being treated using a prophylaxis treatment regimen with a bypass agent, and, participants who have previously received non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) will be considered on a case-by-case basis, only after discussion and agreement between the investigator and the Pfizer medical monitor
* Regular use of immunomodulatory medications (eg, IVIG, routine systemic corticosteroids, rituximab)
* Use of systemic antifibrinolytics, medications that may increase the risk of bleeding, and certain non-steroidal anti-inflammatory drugs within 120 hours of first dose of study intervention and while on study
* Ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention
* Participation in other studies involving investigational drug(s) or investigational vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation
* Previous exposure to marstacimab during participation in other marstacimab clinical studies
* CD4 cell count ≤200/uL if HIV-positive
* Abnormal ECG of clinical relevance that may affect participant safety or interpretation of study results
* Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members

Primary outcomes:
measure: Annualized bleeding rate (ABR) of treated bleeding events
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence of adverse events and serious adverse events
timeFrame: Screening through end of follow-up period (approximately 14 months)
measure: Incidence and severity of thrombotic events
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence and severity of thrombotic microangiopathy
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence and severity of disseminated intravascular coagulation/consumption coagulopathy events
timeFrame: Baseline to end of 12-month treatment period
measure: Immunogenicity (incidence of ADA and clinically significant persistent NAb against marstacimab)
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence and severity of injection site reaction
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence of severe hypersensitivity and anaphylactic reactions
timeFrame: Baseline to end of 12-month treatment period
Secondary outcomes:
measure: Incidence of joint bleeds (treated)
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence of spontaneous bleeds (treated)
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence of target joint bleeds (treated)
timeFrame: Baseline to end of 12-month treatment period
measure: Incidence of total bleeds (treated and untreated)
timeFrame: Baseline to end of 12-month treatment period
measure: Number of target joints
timeFrame: Baseline to end of 12-month treatment period
measure: Change from baseline in joint health as measured by the HJHS for participants ≥4 years of age
timeFrame: Baseline to end of 12-month treatment period
measure: Changes in quality of life measured by Haem-A-QoL/Haemo-QoL (using age-dependent versions for participants ≥8 years of age)
timeFrame: Baseline to end of 12-month treatment period
measure: Changes in quality of life measured by pedHAL (using age-dependent versions for participants ≥4 years of age)
timeFrame: Baseline to end of 12-month treatment period
measure: Changes in quality of life measured by Patient Global Impression of Change - Hemophilia for participants ≥4 years of age
timeFrame: Baseline to end of 12-month treatment period
measure: Changes in quality of life measured by Health Utilities Measure (EQ-5D-Y) for participants ≥4 years of age
timeFrame: Baseline to end of 12-month treatment period
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Intermountain - Primary Children's Hospital
state: Utah
city: Mendoza
country: Argentina
facility: Arbesu Hematología
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Vienna
country: Austria
facility: Medizinische Universität Wien
state: Wien
city: Vitoria
country: Brazil
facility: HEMOES
state: Espírito Santo
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - McMaster University Medical Centre
state: Ontario/canada
city: Beijing
country: China
facility: Beijing Children's hospital, Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of HUST/Pediatric Hematology Department Pharmacy
state: Hubei
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Tianjin
country: China
facility: Institute of hematology&blood disease hospital
state: Tianjin
city: Tianjin
country: China
facility: Institute of hematology&blood disease hospital
state: Tianjin
city: Brno
country: Czechia
facility: Detska nemocnice FN Brno
state: Brno-město
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Hovedstaden
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby
state: Midtjylland
city: Paris
country: France
facility: Hôpital Universitaire Necker Enfants Malades
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Surat
country: India
facility: Nirmal Hospital Pvt Ltd.
state: Gujarat
city: Mumbai
country: India
facility: K.J. Somaiya Hospital
state: Maharashtra
city: Kolkata
country: India
facility: Nil Ratan Sircar Medical College and Hospital
state: WEST Bengal
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
state: Liguria
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù IRCCS
state: Roma
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
city: Kobe
country: Japan
facility: Hyogo prefectural Kobe Children's Hospital
state: Hyogo
city: Azumino
country: Japan
facility: Nagano Children's Hospital
state: Nagano
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Saitama-shi
country: Japan
facility: Saitama Prefectural Children's Medical Center
state: Saitama
city: Saga
country: Japan
facility: Saga University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
state: Seoul-teukbyeolsi [seoul]
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Taegu-kwangyǒkshi
city: Veracruz
country: Mexico
facility: Arké SMO S.A de C.V
city: Dammam
country: Saudi Arabia
facility: King Fahad Specialist Hospital - Dammam
state: ASH Sharqīyah
city: An Narjis
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda
city: Kosice
country: Slovakia
facility: Detska fakultna nemocnica Kosice
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials
state: Gauteng
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Haemophilia Comprehensive Care Centre
state: Gauteng
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Changhua County
country: Taiwan
facility: Changhua Christian Hospital
state: Changhua
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: İstanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi
state: İ̇stanbul
city: Izmir
country: Turkey
facility: Ege Universitesi Hastanesi
state: İ̇zmir
city: Talas
country: Turkey
facility: Erciyes University
state: Kayseri
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Gazi University Health Research and Application Center Gazi Hospital
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tıp Fakultesi Hastaneleri
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: