Brief Title
Emicizumab PUPs and Nuwiq ITI Study
Official Title
Emicizumab PUPs and Nuwiq ITI Study
Brief 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).
Detailed Description
Hemophilia A (HA) is a congenital bleeding disorder caused by deficient or dysfunctional factor VIII (FVIII) which leads to bleeding correlated with severity. Management is focused on FVIII replacement in reaction to a bleed or preventive as prophylaxis. Effective treatment is complicated by the: (1) difficulty to administer standard replacement therapy via intravenous injection especially in infants and young children; and (2) development of inhibitors (FVIII neutralizing antibodies). Inhibitors can increase morbidity and mortality and exponentially raise the cost of health care. Although inherited and environmental risk factors for inhibitor formation have been identified, there is no effective strategy to prevent inhibitors from developing. Emicizumab (HEMLIBRA®) was recently approved by the Food and Drug Administration (FDA) in infants, children, and adults with congenital hemophilia A, with and without inhibitors, and offers hemostatic efficacy while reducing the burden of administration since it is given weekly, biweekly (every 2 weeks), or monthly via subcutaneous (SQ) route compared to the intravenous (IV) route of FVIII. 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).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Cumulative incidence of inhibitors to FVIII
Secondary Outcome
Number of target joint bleeding events over time (≥3 bleeds in the same joint over the last 24 weeks)
Condition
Hemophilia A
Intervention
Nuwiq (low dose protocol)
Study Arms / Comparison Groups
Untreated/minimally treated moderate HA no inhibitors
Description: Previously untreated patients (PUPs) and minimally treated patients (MTPs) <3 years of age with moderately severe (≤2% FVIII) HA and no inhibitors.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
February 17, 2022
Completion Date
April 2025
Primary Completion Date
April 2025
Eligibility 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
Gender
All
Ages
N/A - 21 Years
Accepts Healthy Volunteers
No
Contacts
Robert Sidonio, MD, 404-785-1637, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04030052
Organization ID
IRB00111805
Responsible Party
Principal Investigator
Study Sponsor
Emory University
Collaborators
Genentech, Inc.
Study Sponsor
Robert Sidonio, MD, Principal Investigator, Emory University
Verification Date
February 2022