Prophylaxis Study of Marstacimab in Pediatric Hemophilia Participants With or Without Inhibitors

Phase 1

Recruiting

Conditions: Haemophilia
MedDRA version: 20.0Level: LLTClassification code: 10018939Term: Haemophilia B (Factor IX) Class: 10010331
MedDRA version: 20.0Level: LLTClassification code: 10018938Term: Haemophilia A (Factor VIII) Class: 10010331
MedDRA version: 20.0Level: LLTClassification code: 10018937Term: Haemophilia A Class: 10010331
Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]

Registration Number: CTIS2022-500495-65-00

Lead Sponsor: Pfizer Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Male

Target Recruitment: 100

Inclusion Criteria

Participants must be male, of appropriate age, and of a minimum body weight at the time of signing the informed consent/assent as follows: •For enrollment in the first age group, participant must be =12 to <18 years of age with a minimum body weight of 25 kg at the time of informed consent/assent. •For enrollment in the second age group, participant must be =6 to <12 years of age with a minimum body weight of 19 kg at the time of informed consent/assent. •For enrollment in the third age group, participant must be =1 to <6 years of age at the time of informed consent/assent. The minimum body weight for this age group will be determined based on emerging data from prior enrolled age groups., Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B (FVIII activity <1% or FIX activity =2%, respectively) documented by historical evidence prior to Day 1 Pre-Dose (Visit 2). If the participant’s historical factor activity is not available or documented, the severity of the participant’s hemophilia may be confirmed by a local clinical laboratory or the central laboratory for this study prior to Day 1 Pre-Dose (Visit 2)., Participants who have at least 1 year of diary information 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 informed consent/assent., 4.Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria: •No detectable inhibitor (=0.6 BU/mL at the central testing lab) against FVIII or FIX prior to Day 1 Pre-Dose (Visit 2). •No documented history of high titer inhibitors (=5 BU/mL or greater than the ULN for the testing laboratory) against FVIII or FIX in the 5 years prior to the time of informed consent/assent. •No low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with recovery <60% of expected in the 5 years prior to the time of informed consent/assent. •For participants who have undergone ITI, successful completion of ITI at least 5 years prior to the time of informed consent/assent and no evidence of inhibitor recurrence (permanent or temporary) as indicated by detection of an inhibitor, or FVIII or FIX recovery <60% since completing ITI. •Participants who have at least 50 documented exposure days to FVIII/FIX replacement product (recombinant, plasma-derived, or long-acting FIX product). •Participants must be on a stable routine prophylaxis regimen (defined as treatment by IV injection of factor concentrate to prevent bleeding) with FVIII/FIX replacement and have demonstrated at least 80% compliance with a stable prophylaxis regimen. a.Participants must be on a stable prophylaxis regimen during the 12 months prior to informed consent/assent. b.Exogenous FVIII/FIX replacement infusions and hemophilic bleeding episodes were documented over the previous 12 months prior to the time of informed consent/assent., 5.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 informed consent/assent. •Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the high quantitative i

Exclusion Criteria

Known coronary artery, thrombotic, or ischemic disease, including congenital or acquired thrombophilic disease such as Anti-thrombin III, Factor V Leiden mutation, prothrombin 20210 mutation, protein C activity, protein S activity and antiphospholipid syndrome., 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., Screening 12-lead ECG, interpreted by a central reader, that demonstrates clinically relevant abnormalities 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., Known planned surgical procedure during the planned study period., Known hemostatic defect other than hemophilia A or B., Abnormal renal or hepatic function as defined by any of the following laboratory results at screening: a.ALT >2 × ULN. b.Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). c.Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -eg, presence of HBsAg or positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention) is acceptable if the participant otherwise meets entry criteria. d.Serum albumin less than the LLN. e.Adolescents (=12 to <18 years) with estimated CrCl <30 ml/min (by Cockcroft-Gault Formula performed by central lab; see Appendix 2 Table 3 for calculation); f.Children (=6 to <12 years) with estimated CrCl <30 ml/min/1.73m2 (by Modified Schwartz Equation performed by central lab; see Appendix 2 Table 3 for calculation)., Abnormal hematology values as defined by the following laboratory tests at Screening: •Platelet count <100,000/uL •Hemoglobin level <10 g/dL •Fibrinogen level 1.25 × ULN., Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality 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, would make the participant inappropriate for entry into this study., Individuals with known allergic reaction or hypersensitivity to hamster protein or other components of the study intervention., Current routine prophylaxis with bypassing agent (eg, aPCC, BYCLOT, PCC, or rFVIIa), 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 will be considered on a case-by-case basis, only afte

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the efficacy and safety of marstacimab for routine prophylaxis in severe hemophilia A or moderately severe to severe hemophilia B (FVIII activity <1% or FIX activity =2%, respectively) participants 1 to <18 years of age with or without inhibitors.;Secondary Objective: To evaluate additional efficacy of marstacimab., To evaluate the effect of marstacimab on HRQoL.;Primary end point(s): The primary efficacy endpoint is the ABR of treated bleeding events., Safety Endpoints:•AEs and SAEs •Incidence and severity of thrombotic events •Incidence and severity of thrombotic microangiopathy •Disseminated intravascular coagulation/consumption coagulopathy •Immunogenicity (incidence of ADA and clinically significant persistent NAb against marstacimab) •Incidence and severity of injection site reaction •Incidence of severe hypersensitivity and anaphylactic reactions

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):The following parameters will be assessed: •Incidence of joint bleeds (treated) •Incidence of spontaneous bleeds (treated) •Incidence of target joint bleeds (treated) •Incidence of total bleeds (treated and untreated) •Number of target joints •Change from baseline in joint health as measured by the HJHS for participants =4 years of age;Secondary end point(s):HRQoL: •Haem-A-QoL (=17 years of age)/Haemo-QoL (age-dependent versions =12 to <17 years of age and 8 to <12 years of age) •pedHAL (children/teenager version 8 to =17 years of age, parent proxy version 4 to <8 years of age) •PGIC-H for participants =4 years of age •Health Utilities Measure (EQ-5D-Y) for participants =4 years of age