Emicizumab PUPs and Nuwiq ITI Study

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

Start Date

May 2021

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

April 2021