Clinical trial NCT05145127: Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Official title: AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF MARSTACIMAB PROPHYLAXIS IN 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
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-12-06
Enrollment: 245
Sex: MALE
Minimum age (years): 1
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study B7841007 is an open-label extension study to assess the long-term safety, tolerability, and efficacy of prophylaxis treatment with marstacimab in participants who did not require "Early Termination" from the Phase 3 Study B7841005 and from the Phase 3 Study B7841008.

Study B7841005: approximately 145 adolescent and adult participants 12 to \<75 years of age with severe hemophilia A or moderately severe to severe hemophilia B (defined as FVIII activity \<1% or FIX activity ≤2%, respectively) with or without inhibitors are expected to be enrolled in Study B7841005 during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab).

Study B7841008: this is an ongoing Phase 3, open-label study in pediatric participants \<18 years of age with severe hemophilia A (FVIII Coagulation Factor Activity \<1%) or moderately severe to severe hemophilia B (FIX Coagulation Factor Activity ≤2%). A sequential approach will be used in enrolling at least 100 pediatric participants, at least 20 of which will be aged ≥12 to \<18 years and at least 80 participants will be aged ≥1 to \<12 years. At the start of study B7841008, the dosing and data available in adolescent and adult participants in Study B7841005 supported the initiation of B7841008 study in participants aged ≥12 to \<18 years. Subsequently, additional safety and efficacy data from adolescent participants in Study B7841005 became available for benefit/risk assessment in support of dosing participants aged ≥6 to \<12 years. Based on the positive benefit/risk assessment conducted by both internal Pfizer review and eDMC review, dosing of the ≥6 to \<12 years age group was initiated in June 2023 in B7841008 Study. Data from participants ≥6 years from B7841008 Study and Study B7841005 will support the dosing of participants aged ≥1 to \<6 years.

All participants will be provided the prefilled pen (PFP) for administration of marstacimab in the study. Use of the prefilled syringe (PFS) will be permitted at the investigator's discretion for those participants who have difficulty with administration of the PFP. Additionally, participants will be provided the PFS for use in this study in countries where the PFS is anticipated to be the only presentation available commercially. An optional, open-label, single arm, substudy using the PFP was completed in the first 23 participants rolled over from Study B7841005 who agreed to participate in the substudy.


Eligibility criteria: Inclusion Criteria:

* All participants will have a minimum body weight as defined by parent studies
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Participants have successfully completed participation in parent studies, defined as did not require "Early Termination"

Exclusion Criteria:

* Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade \>3), or ischemic disease (except catheter-associated thrombosis)
* Abnormal renal function as defined by eGFR \<30 mL.min/1.73 m(2)
* Known planned surgical procedure during the planned study period
* Unstable hepatic function as determined by the Investigator clinical assessment and review of the participant's most recent laboratory results, which would make the participant inappropriate for the study
* For participants known to be HIV+, worsening disease status as determined by the Investigator clinical assessment and review of participant's most recent laboratory results, to include recent locally available CD4 count (if available), which would make the participant inappropriate for the study
* Regular, concomitant therapy with immunomodulatory drugs (eg, IVIG, and routine systemic corticosteroids, rituximab)
* Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study
* Participation in other study involving investigational drug(s) or investigational vaccine(s) within 30 days or 5 half-lives prior to or during study participation, with the exception of participation in parent studies
* Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the Investigator, and their respective family members

Primary outcomes:
measure: Number of subject reporting Adverse Events
timeFrame: Baseline up to 7 years
measure: Number of subjects reporting Serious Adverse Events
timeFrame: Baseline up to 7 years
measure: Incidence and severity of thrombotic events
timeFrame: Baseline up to 7 years
measure: Incidence and severity of thrombotic microangiopathy
timeFrame: Baseline up to 7 years
measure: Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy
timeFrame: Baseline up to 7 years
measure: Incidence of clinically significant persistent NAb against marstacimab
timeFrame: Baseline up to 7 years
measure: Incidence and severity of injection site reaction
timeFrame: Baseline up to 7 years
measure: Clinically significant changes in vital signs from baseline
timeFrame: Baseline up to 7 years
measure: Incidence of clinically significant laboratory value abnormalities
timeFrame: Baseline up to 7 years
measure: Incidence of severe hypersensitivity and anaphylactic reactions
timeFrame: Baseline up to 7 years
Secondary outcomes:
measure: Annualized rate of bleeding episodes
timeFrame: Baseline up to 7 years
measure: Total coagulation factor product consumption
timeFrame: Baseline up to 7 years
measure: Incidence of joint bleeds
timeFrame: Baseline up to 7 years
measure: Incidence of spontaneous bleeds
timeFrame: Baseline up to 7 years
measure: Incidence of target joint bleeds
timeFrame: Baseline up to 7 years
measure: Incidence of total bleeds (treated and untreated)
timeFrame: Baseline up to 7 year
measure: Change in joints measured by the HJHS
timeFrame: Baseline up to 7 years
measure: Change in number of target joints per subject from baseline
timeFrame: Baseline up to 7 years
measure: Changes in Health Utilities Measure questionnaire data
timeFrame: Baseline up to 7 years
measure: Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age
timeFrame: Baseline up to 7 years
measure: Changes in Haemo-QoL questionnaire data
timeFrame: Baseline up to 7 years
measure: Total bypass product consumption
timeFrame: Baseline up to 7 years
measure: Changes in EQ-5D questionnaire data
timeFrame: Baseline up to 7 years
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Hyde Park
country: United States
facility: Northwell Health HTC
state: New York
city: Seattle
country: United States
facility: Washington Institute for Coagulation d/b/a WACBD
state: Washington
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - McMaster University Medical Centre
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - McMaster University Medical Centre
state: Ontario
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical,Science & Technology
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: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
city: Paris
country: France
facility: Hôpital Universitaire Necker Enfants Malades
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Surat
country: India
facility: Nirmal Hospital Pvt Ltd.
state: Gjuarat
city: Mumbai
country: India
facility: K.J. Somaiya Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality 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: Roma
country: Italy
facility: AOU Policlinico Umberto I
state: RM
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Nagoya
country: Japan
facility: Nagoya University Hospital - Transfusion Medicine
state: Aichi
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 Children's Medical Center
state: Saitama
city: Hiroshima
country: Japan
facility: Hiroshima 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: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi[seoul]
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Taegu-kwangyǒkshi
city: Merida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan
state: Yucatán
city: Merida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatán S.
state: Yucatán
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Belgrade
country: Serbia
facility: Institute for Mother and Child healthcare "Dr Vukan Cupic"
city: Nis
country: Serbia
facility: Clinical Center Nis
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: Benoni
country: South Africa
facility: Worthwhile Clinical Trials
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
city: A Coruna
country: Spain
facility: Hospital Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron
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 City
country: Taiwan
facility: ChangHua Christian Hospital
state: Changhua County
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Ankara
country: Turkey
facility: Gazi University Health Research and Application Center Gazi Hospital
city: Gaziantep
country: Turkey
facility: Gaziantep University Şahinbey Research and Practice Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Oncology Institute
city: Izmir
country: Turkey
facility: Ege University Faculty of Medicine
city: Izmir
country: Turkey
facility: Ege University Faculty of Medicine
city: Kayseri
country: Turkey
facility: Erciyes University Faculty of Medicine
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University Healthcare Practice and Research Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: