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Preventing Inhibitor Recurrence Indefinitely (PRIORITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04621916
Recruitment Status : Active, not recruiting
First Posted : November 9, 2020
Last Update Posted : March 9, 2022
Sponsor:
Collaborator:
Grifols Biologicals, LLC
Information provided by (Responsible Party):
Guy Young, Children's Hospital Los Angeles

Brief Summary:

This study will enroll children who have hemophilia A with inhibitors who successfully completed immune tolerance induction per the ISTH criteria (negative inhibitor titer, recovery >66% of expected, and half-life of >6 hours with their current FVIII concentrate). Previous to emicizumab, there was only one option for these patients which was to continue FVIII therapy in a prophylaxis mode to prevent bleeding. There was a sense that the ongoing FVIII served to maintain tolerance however no evidence for this notion exists and in fact what limited data is available suggests that continuing FVIII may not be necessary simply to maintain tolerance.

To figure out this question, this will be a randomized, controlled 2 arm study which will randomize patients post-successful ITI to emicizumab plus weekly FVIII (for maintenance of tolerance) versus emicizumab alone. Patients will be followed for up to 2 years. We aim to enroll 52 subjects. The FVIII weekly arm can use any factor VIII concentrate and emicizumab is standard of care for inhibitor and non-inhibitor patients.


Condition or disease Intervention/treatment Phase
Hemophilia A Immune Tolerance Drug: FVIII Drug: Emicizumab Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multi-center, Prospective Study Evaluating the Rate of Inhibitor Recurrence Following Successful ITI in Patients Receiving Ongoing Once Per Weekly Factor VIII Therapy Along With Emicizumab and in Patients Who Discontinue FVIII Therapy and Are on Emicizumab for Prophylaxis
Actual Study Start Date : September 21, 2020
Estimated Primary Completion Date : September 21, 2022
Estimated Study Completion Date : September 21, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
Active Comparator: Emicizumab + FVIII weekly
In addition to emicizumab prophylaxis,participants will receive non-prophylactic exposure to FVIII concentrates through weekly 50 IU/kg ±10% doses - the choice of FVIII concentrate is at the discretion of the PI.
Drug: FVIII
This study will evaluate the inhibitor recurrence with or without ongoing FVIII exposure in patients with hemophilia A on emicizumab prophylaxis after a successful immune tolerance induction.

Drug: Emicizumab
This study will evaluate the inhibitor recurrence with or without ongoing FVIII exposure in patients with hemophilia A on emicizumab prophylaxis after a successful immune tolerance induction.

Active Comparator: Emicizumab only
Participants will only receive emicizumab prophylaxis.
Drug: Emicizumab
This study will evaluate the inhibitor recurrence with or without ongoing FVIII exposure in patients with hemophilia A on emicizumab prophylaxis after a successful immune tolerance induction.




Primary Outcome Measures :
  1. Inhibitor recurrence [ Time Frame: The goal is to complete all study procedures in 2 years. ]
    FVIII inhibitor level will be checked on certain time points during the study.



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Ages Eligible for Study:   up to 12 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Since Hemophilia is a X-linked bleeding disorder occurring mostly in males we expected to mostly enroll male-identified subjects.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≤12 years at the time of signing the informed consent
  2. Male patients with severe (<1%) or moderate (<2%) hemophilia A
  3. History of a high titer (>5 BU) inhibitor
  4. Within 1 year of successful ITI, according to ISTH definitions (inhibitor titer <0.6 BU, recovery more than 60% of expected, and half-life of >6 hours). Successful ITI has been achieved with any FVIII concentrate.
  5. Currently on emicizumab or willing to alter their prophylaxis treatment to emicizumab per study protocol.

Exclusion Criteria:

  1. Age >12 years at the time of signing the informed consent
  2. Partial tolerance (not meeting criteria for complete tolerance per ISTH)
  3. History of anti-drug antibodies to emicizumab
  4. Unwilling to receive exposure to intravenous FVIII concentrates.
  5. History per the investigator's discretion of non-compliance to prior therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04621916


Locations
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United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Grifols Biologicals, LLC
Investigators
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Principal Investigator: Guy Young, MD Professor of Pediatrics, Director of Hemostasis and Thrombosis Center
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Responsible Party: Guy Young, MD, professor, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT04621916    
Other Study ID Numbers: CHLA-20-00189
First Posted: November 9, 2020    Key Record Dates
Last Update Posted: March 9, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All individual participant data will be in the results of the study publication.
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Recurrence
Disease Attributes
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn