Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05145127
• Other study ID #: B7841007
• Secondary ID: PHASE 3 ANTI-TFP
• Status: Recruiting
• Phase: Phase 3
• Start date: November 17, 2021
• Est. completion date: July 31, 2030

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 145
• Est. completion date: July 31, 2030
• Est. primary completion date: July 31, 2030
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 1 Year to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Drug:
• PF-06741086
For participants aged =12 years 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. For participants aged =6 to <12 years is marstacimab 150 mg SC for initial loading dose followed by 75 mg SC QW. 150 mg sc qw is prescribed for participants who meet dose escalation criteria.

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences - McMaster University Medical Centre	Hamilton	Ontario
Canada	Hamilton Health Sciences - McMaster University Medical Centre	Hamilton	Ontario
China	Beijing Children's Hospital, Capital Medical University	Beijing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Institute of hematology&blood disease hospital	Tianjin	Tianjin
Croatia	Klinicki bolnicki centar Zagreb	Zagreb
France	Hôpital Universitaire Necker Enfants Malades	Paris
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
India	K.J. Somaiya Hospital	Mumbai	Maharashtra
India	Sahyadri Super Speciality Hospital	Pune	Maharashtra
India	Nirmal Hospital Pvt Ltd.	Surat	Gjuarat
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	AOU Policlinico Umberto I	Roma	RM
Japan	Hiroshima University Hospital	Hiroshima
Japan	Nagoya University Hospital - Transfusion Medicine	Nagoya	Aichi
Korea, Republic of	Kyungpook National University Hospital	Daegu	Taegu-kwangyokshi
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi[seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [seoul]
Mexico	Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan	Merida	Yucatán
Mexico	Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatán S.	Merida	Yucatán
Oman	Sultan Qaboos University Hospital	Muscat
Serbia	Institute for Mother and Child healthcare "Dr Vukan Cupic"	Belgrade
Serbia	Clinical Center Nis	Nis
South Africa	Worthwhile Clinical Trials	Benoni	Gauteng
South Africa	Worthwhile Clinical Trials	Benoni
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
Spain	Hospital Universitario A Coruna	A Coruna
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	ChangHua Christian Hospital	Changhua City	Changhua County
Taiwan	Taichung Veterans General Hospital	Taichung
Turkey	Acibadem Adana Hospital	Adana
Turkey	Gazi University Health Research and Application Center Gazi Hospital	Ankara
Turkey	Hacettepe University Faculty of Medicine	Ankara
Turkey	Gaziantep University Sahinbey Research and Practice Hospital	Gaziantep
Turkey	Istanbul University Oncology Institute	Istanbul
Turkey	Ege University Faculty of Medicine	Izmir
Turkey	Ege University Faculty of Medicine	Izmir
Turkey	Erciyes University Faculty of Medicine	Kayseri
Turkey	Ondokuz Mayis University Healthcare Practice and Research Center	Samsun
United States	University of Iowa	Iowa City	Iowa
United States	Northwell Health HTC	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  China,  Croatia,  France,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Oman,  Serbia,  South Africa,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subject reporting Adverse Events		Baseline up to 7 years
Primary	Number of subjects reporting Serious Adverse Events		Baseline up to 7 years
Primary	Incidence and severity of thrombotic events		Baseline up to 7 years
Primary	Incidence and severity of thrombotic microangiopathy		Baseline up to 7 years
Primary	Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy		Baseline up to 7 years
Primary	Incidence of clinically significant persistent NAb against marstacimab		Baseline up to 7 years
Primary	Incidence and severity of injection site reaction		Baseline up to 7 years
Primary	Clinically significant changes in vital signs from baseline		Baseline up to 7 years
Primary	Incidence of clinically significant laboratory value abnormalities		Baseline up to 7 years
Primary	Incidence of severe hypersensitivity and anaphylactic reactions		Baseline up to 7 years
Secondary	Annualized rate of bleeding episodes	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)	Baseline up to 7 years
Secondary	Total coagulation factor product consumption		Baseline up to 7 years
Secondary	Incidence of joint bleeds		Baseline up to 7 years
Secondary	Incidence of spontaneous bleeds		Baseline up to 7 years
Secondary	Incidence of target joint bleeds		Baseline up to 7 years
Secondary	Incidence of total bleeds (treated and untreated)		Baseline up to 7 year
Secondary	Change in joints measured by the HJHS	Change in joints as measured by the HJHS for participants =4 years of age	Baseline up to 7 years
Secondary	Change in number of target joints per subject from baseline		Baseline up to 7 years
Secondary	Changes in Health Utilities Measure questionnaire data		Baseline up to 7 years
Secondary	Changes in Haem-A-QoL questionnaire data for participants =17 years of age		Baseline up to 7 years
Secondary	Changes in Haemo-QoL questionnaire data	Haemo-QoL CII (Ages 8 to <12 years), Haemo-QoL (Ages 12 to <17),	Baseline up to 7 years
Secondary	Total bypass product consumption		Baseline up to 7 years
Secondary	Changes in EQ-5D questionnaire data	EQ-5D-Y Proxy (Ages = 4 to = 6 years), EQ-5D-Y Self (Ages = 7 to = 11 years), EQ-5D-5L (Ages =12)	Baseline up to 7 years

External Links

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