Hemophilia A or B MedDRA version: 20.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: PF-06741086, MARSTACIMAB 150mg/ml
Product Code: PF-06741086
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Marstacimab
Current Sponsor code: PF-06
Sponsors
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be male and 12 to =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Previous or current treatment for or history of coronary artery diseases, venous or arterial thrombosis (Common Terminology Criteria for Adverse Events [CTCAE] Grade >1), or ischemic disease (except treatment for catheter associated thrombosis). 2. Known planned surgical procedure during the planned study period. 3. Known hemostatic defect other than hemophilia A or B. 4. Abnormal renal or hepatic function as defined by the following laboratory results at Screening: a. Alanine transaminase (ALT) >2 × upper limit of normal (ULN) b. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 450 msec for male participants or QTc >480 msec in participants with bundle branch block. 8. Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention. Prior/Concomitant Therapy 9. Current routine prophylaxis with bypassing agent (eg, aPCC, BYCLOT, Prothrombin Complex Concentrates [PCC], or rFVIIa) or non-coagulation non-factor replacement therapy (eg, emicizumab). 10. Regular, concomitant therapy with immunomodulatory drugs (eg, IV immunoglobulin [IVIG], and routine systemic corticosteroids, rituximab). 11. Ongoing or planned use of immune tolerance induction during the Observational Phase or Active Treatment Phase, or prophylaxis with FVIII or FIX replacement during the Active Treatment Phase. Prior/Concurrent Clinical Study Experience 12. Participation in other studies involving investigational drug(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation. 13. Previous exposure to PF 06741086 during to participation in studies B7841002 and B7841003. Diagnostic assessments 14. CD4 cell count =200/uL if human immunodeficiency virus (HIV)-positive 15. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study result
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy and safety of PF06741086 for routine prophylaxis in severe (FVIII or FIX activity <1%) hemophilia A or B patients 12 to <75 years of age with or without inhibitors;Secondary Objective: To evaluate additional efficacy of PF06741086;Primary end point(s): Primary Efficacy Endpoint The primary efficacy endpoint is the annualized bleeding rate (ABR) of treated bleeding events, which is derived for each participant for each treatment period by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25). The statistical objective and strategy of demonstrating the efficacy in each cohort is shown below. Inhibitor Cohort: In all regions, to demonstrate superiority in ABR of PF-06741086 prophylaxis observed over the 12 month Active Treatment Phase versus on demand treatment with bypass therapy during the 6 months prior to receiving study intervention. Non-Inhibitor Cohort: For regions outside the European Union (EU), superiority in ABR of PF 06741086 prophylaxis observed over the 12-month Active Treatment Phase versus on-demand treatment with FVIII- or FIX- replacement during the Observational Phase prior to receiving study intervention. For the EU, non-inferiority in ABR of PF 06741086 prophylaxis observed over the 12 month Active Treatment Phase versus prophylaxis treatment with FVIII- or FIX-replacement during the Observational Phase prior to receiving study intervention. Safety Endpoints Type I error control would not be applied to the following safety endpoints: Adverse events (AEs) and SAEs Incidence and severity of thrombotic events Incidence and severity of thrombotic microangiopathy Disseminated intravascular coagulation/consumption coagulopathy Immunogenicity (incidence of anti drug antibody [ADA] and clinically significantly persistent neutralizing antibody [NAb] against PF 06741086) Incidence and severity of injection site reaction Changes in physical examination an | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints The following parameters will be assessed for comparison between PF-06741086 prophylaxis observed over the 12-month Active Treatment Phase versus a respective control group corresponding to each of the 3 statistical objectives (inhibitors, non-inhibitors for regions outside EU, and non-inhibitors for the EU). For the Non-Inhibitor Cohort, all the primary and secondary endpoints for regions outside of the EU will be part of the secondary endpoints for the EU and vice versa. Total coagulation factor or bypass product consumption Incidence of joint bleeds Incidence of spontaneous bleeds Incidence of target joint bleeds Incidence of total bleeds (treated and untreated). Percentage of participants with no bleeding episodes Change in joints as measured by the Hemophilia Joint Health Score (HJHS) HRQoL: • Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) (=17 years of age)/Hemophilia Quality of Life Questionnaire for Children (Haemo-QoL); (Adolescents 12 to <17 years of age); • Hemophilia Activities List (HAL) (Adult =17 years of age)/Pediatric Hemophilia Activities List (pedHAL) (Adolescents 12 to <17 years of age); • Patient Global Impression of Change – Hemophilia (PGIC-H) (Observational Phase and Active Treatment Phase) • Health Utilities Measure (EuroQol 5 Dimensions 5 Level [EQ-5D-5L]) Tertiary/Exploratory Objectives Analysis of PF 06741086 (marstacimab) concentrations (trough as well as post-dose) over the duration of the study Analysis of changes in biomarkers: TFPI (total and free), peak thrombin generation [PKT], prothrombin fragment 1+2 [PF1+2], D-dimer, and dilute prothrombin time over duration of the study ;Timepoint(s) of evaluation of this end point: Timepoints are all listed in the list of primary endpoints. | — |
Countries
Australia, Brazil, Bulgaria, Canada, China, Croatia, France, Germany, Hong Kong, India, Ireland, Italy, Japan, Korea, Republic of, Mexico, Oman, Russian Federation, Saudi Arabia, Serbia, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed