Emicizumab PUPs and Nuwiq ITI Study

• Status: Recruiting
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study prospectively investigates the safety, FVIII immunogenicity, and hemostatic efficacy of prophylactic HEMLIBRA® given with a concomitant low dose recombinant factor VIII (rFVIII) known as NUWIQ®, in HA infants and children <3 years old who have had little to no previous exposure to FVIII. In addition, the study investigates the safety and efficacy of a novel FVIII ITI regimen in children <21 with existing low and high titer inhibitors (LTI and HTI).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: Genentech, Inc.
• Treatments: Antibodies, Bispecific; Factor VIII

Criteria

Inclusion Criteria - Part A:

• Moderately severe (≤2% FVIII) hemophilia A

• <3 Years of age at the time of informed consent

• Caregiver (parent or legal guardian) has provided written informed consent

• ≤2 EDs to pdFVIII, rFVIII, or a single dose of FFP, Cryoprecipitate or PRBCs.

• Adequate hematologic function (HgB >8 g/dL and platelet count >100,000 µL)

• Adequate hepatic function (total bilirubin ≤1.5x ULN and both AST/ALT ≤3x ULN at screening (excluding known Gilbert's)

• Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)

• Negative test for inhibitor (<0.6 BU/mL) with a 72-hour washout within 4 weeks of enrollment

• No documented FVIII inhibitor since birth *Participants will be encouraged to co-enroll in the ATHN 8 Study

Inclusion Criteria - Part B

• Moderately severe (≤2% FVIII) hemophilia A

• <21 Years of age at the time of informed consent

• Documented on 2 occasions a persistent low (>0.6 BU/mL) or high titer inhibitor (>5 BU/mL) with a 72-hour washout within 8 weeks of enrollment after either the first time ITI or after single attempt of <6 months of continuous 3x/week factor ITI

• Caregiver and/or participant provided written informed consent

• Adequate hematologic function (HgB >8 g/dL and platelet count >100,000 µL)

• Adequate hepatic function (total bilirubin ≤1.5x ULN and both AST/ALT ≤3x ULN at screening (excluding known Gilbert's)

• Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)

Exclusion Criteria - Part A and B

• Inherited or acquired bleeding disorder other than severe hemophilia A (participants with previous documentation of low von Willebrand factor (vWF) defined as vWF antigen and vWF ristocetin cofactor both between 40-50 will be permitted)

• Previous or current treatment for thromboembolic disease or signs of thromboembolic disease

• Conditions that may increase risk of bleeding or thrombosis. Will not require or request a thrombophilia evaluation

• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the HEMLIBRA® injection (with the exception of rituximab)

• Known HIV infection with CD4 count <200 cells/µL within 24 weeks prior to screening. Testing not required if can demonstrate negative testing in mother prior to pregnancy

• Use of systemic immunomodulators at enrollment or planned use during the study

• Participants who are at high risk for thrombotic microangiopathy (TMA) (for example, have a previous medical or family history of TMA), in the investigator's judgment

• Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study

• Planned surgery (excluding minor procedures or central line placement) during the study

• Receipt of HEMLIBRA® as part of a prior investigational study; an investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration; a non-hemophilia-related investigational drug concurrently, within last 30 days or 5 half-lives, whichever is shorter