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

• ClinicalTrials.gov Identifier: NCT05145127
• Recruitment Status: Recruiting
• First Posted: December 6, 2021
• Last Update Posted: January 23, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 11, 2021
• First Posted Date: December 6, 2021
• Last Update Posted Date: January 23, 2023
• Actual Study Start Date: November 17, 2021
• Estimated Primary Completion Date: July 31, 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 13, 2021)

• Number of subject reporting Adverse Events [ Time Frame: Baseline up to 7 years ]
• Number of subjects reporting Serious Adverse Events [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of thrombotic events [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of thrombotic microangiopathy [ Time Frame: Baseline up to 7 years ]
• Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy [ Time Frame: Baseline up to 7 years ]
• Incidence of clinically significant persistent NAb against marstacimab [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of injection site reaction [ Time Frame: Baseline up to 7 years ]
• Clinically significant changes in vital signs from baseline [ Time Frame: Baseline up to 7 years ]
• Incidence of clinically significant laboratory value abnormalities [ Time Frame: Baseline up to 7 years ]
• Incidence of severe hypersensitivity and anaphylactic reactions [ Time Frame: Baseline up to 7 years ]

Original Primary Outcome Measures (submitted: December 1, 2021)

• Number of subject reporting Adverse Events [ Time Frame: Baseline up to 7 years ]
• Number of subjects reporting Serious Adverse Events [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of thrombotic events [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of thrombotic microangiopathy [ Time Frame: Baseline up to 7 years ]
• Number of subjects reporting Disseminated intravascular coagulopathy/consumption coagulopathy [ Time Frame: Baseline up to 7 years ]
• Incidence of clinically significant persistent NAb against marstacimab [ Time Frame: Baseline up to 7 years ]
• Incidence and severity of injection site reaction [ Time Frame: Baseline up to 7 years ]
• Clinically significant changes in vital signs from baseline [ Time Frame: Baseline up to 7 years ]
• Incidence of clinically significant laboratory value abnormalities [ Time Frame: Baseline up to 7 years ]
• Incidence of severe hypersensitivity and anaphylactic reactions [ Time Frame: Baseline up to 7 years ]

Current Secondary Outcome Measures (submitted: January 19, 2023)

• Annualized rate of bleeding episodes [ Time Frame: Baseline up to 7 years ]
  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)
• Total coagulation factor product consumption [ Time Frame: Baseline up to 7 years ]
• Incidence of joint bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of spontaneous bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of target joint bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of total bleeds (treated and untreated) [ Time Frame: Baseline up to 7 year ]
• Change in joints measured by the HJHS [ Time Frame: Baseline up to 7 years ]
• Change in number of target joints per subject from baseline [ Time Frame: Baseline up to 7 years ]
• Changes in Health Utilities Measure questionnaire data [ Time Frame: Baseline up to 7 years ]
• Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age [ Time Frame: Baseline up to 7 years ]
• Changes in Haemo-QoL questionnaire data for participants 12 to <17 years of age [ Time Frame: Baseline up to 7 years ]
• Total bypass product consumption [ Time Frame: Baseline up to 7 years ]

Original Secondary Outcome Measures (submitted: December 1, 2021)

• Annualized rate of bleeding episodes [ Time Frame: Baseline up to 7 years ]
  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)
• Total coagulation factor product consumption [ Time Frame: Baseline up to 7 years ]
• Incidence of joint bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of spontaneous bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of target joint bleeds [ Time Frame: Baseline up to 7 years ]
• Incidence of total bleeds (treated and untreated) [ Time Frame: Baseline up to 7 year ]
• Percentage of participants with no bleeding episodes [ Time Frame: Baseline up to 7 years ]
• Change in joints measured by the HJHS [ Time Frame: Baseline up to 7 years ]
• Change in number of target joints per subject from baseline [ Time Frame: Baseline up to 7 years ]
• Changes in Health Utilities Measure questionnaire data [ Time Frame: Baseline up to 7 years ]
• Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age [ Time Frame: Baseline up to 7 years ]
• Changes in Haemo-QoL questionnaire data for participants 12 to <17 years of age [ Time Frame: Baseline up to 7 years ]
• Total bypass product consumption [ Time Frame: Baseline up to 7 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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. 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 this study during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab). The dosing regimen of marstacimab is 150 mg SC once weekly.

All participants will be provided the PFP for administration of marstacimab in the study. Use of the 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. In addition, an optional, open-label, single arm, substudy using the PFP will be administered to the first approximately 20 participants rolling over from Study B7841005 who agree to participate in the substudy.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hemophilia A
• Hemophilia B

Intervention

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.

Other Name: marstacimab

Study Arms

Experimental: 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.

Intervention: Drug: PF-06741086

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 1, 2021): 145
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2030
• Estimated Primary Completion Date: July 31, 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• All participants will have a minimum body weight of 35 kg
• Participants have successfully completed participation in study B7841005, defined as did not require "Early Termination" from study B7841005

Exclusion Criteria:

• Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade >3), or ischemic disease (except catherter-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 study B7841005
• 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

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Male participants only

• Ages: 12 Years to 74 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Canada, Croatia, France, Hong Kong, India, Japan, Korea, Republic of, Mexico, Oman, Serbia, Spain, Taiwan, Turkey, United States
• Removed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT05145127
• Other Study ID Numbers: B7841007; PHASE 3 ANTI-TFPI OLE ( Other Identifier: Alias Study Number ); 2022-500470-33-00 ( Registry Identifier: CTIS(EU) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2023