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A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors (HAVEN 2)

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ClinicalTrials.gov Identifier: NCT02795767
Recruitment Status : Active, not recruiting
First Posted : June 10, 2016
Last Update Posted : November 9, 2018
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This non-randomized, multicenter, open-label, Phase III clinical study will evaluate the efficacy, safety, and pharmacokinetics of emicizumab administered subcutaneously initially once weekly (QW) in pediatric participants with hemophilia A with FVIII inhibitors. This study will open two additional non-randomized cohorts to investigate Q2W and Q4W regimens in pediatric participants.

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: Emicizumab Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors
Actual Study Start Date : July 22, 2016
Actual Primary Completion Date : April 30, 2018
Estimated Study Completion Date : February 5, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
Experimental: Cohort A: Emicizumab QW
Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.
Drug: Emicizumab
Emicizumab will be administered as per the schedule specified in the respective arm.
Other Name: RO5534262

Experimental: Cohort B: Emicizumab Q2W
Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.
Drug: Emicizumab
Emicizumab will be administered as per the schedule specified in the respective arm.
Other Name: RO5534262

Experimental: Cohort C: Emicizumab Q4W
Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.
Drug: Emicizumab
Emicizumab will be administered as per the schedule specified in the respective arm.
Other Name: RO5534262




Primary Outcome Measures :
  1. Number of Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]

Secondary Outcome Measures :
  1. Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time [ Time Frame: Baseline up to 52 weeks ]
  2. Number of Treated Spontaneous Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  3. Number of Treated Joint Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  4. Number of Treated Target Joint Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  5. Cohort A: Reduction From Baseline in Number of Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  6. Cohort A: Reduction From Baseline in Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time [ Time Frame: Baseline up to 52 weeks ]
  7. Cohort A: Reduction From Baseline in Number of Treated Spontaneous Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  8. Cohort A: Reduction From Baseline in Number of Treated Joint Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  9. Cohort A: Reduction From Baseline in Number of Treated Target Joint Bleeds Over Time [ Time Frame: Baseline up to 52 weeks ]
  10. Number of Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to 52 weeks ]
  11. Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time Based on Up-Titration [ Time Frame: Baseline up to 52 weeks ]
  12. Number of Treated Spontaneous Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to 52 weeks ]
  13. Number of Treated Joint Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to 52 weeks ]
  14. Number of Treated Target Joint Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to 52 weeks ]
  15. Percentage of Participants With Adverse Events (AEs) [ Time Frame: From Baseline up to end of study (up to approximately 152 weeks) ]
  16. Percentage of Participants With Anti-Emicizumab Antibodies [ Time Frame: Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until end of study or 24 weeks after treatment discontinuation (up to approximately 152 weeks) ]
  17. Plasma Trough Concentration (Ctrough) of Emicizumab [ Time Frame: Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57; then every 12 weeks until end of study or 24 weeks after treatment discontinuation (up to approximately 152 weeks) ]
  18. Change From Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37; every 8 weeks from Week 41, every 12 weeks from Week 57 until end of study or 24 weeks after treatment discontinuation (up to approximately 152 weeks) ]
  19. Change From Baseline in FVIII Activity [ Time Frame: Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37; every 8 weeks from Week 41, every 12 weeks from Week 57 until end of study or 24 weeks after treatment discontinuation (up to approximately 152 weeks) ]
  20. Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Score, as Completed by Participants of 8 to 17 Years of Age [ Time Frame: Weeks 1, 13, 25, 37, 49, 57; then every 24 weeks until end of study (up to approximately 152 weeks) ]
  21. Adapted Hemophilia-Specific Quality of Life for Participants with Inhibitors Including Aspects of Caregiver Burden (Inhib-QoL) Questionnaire Score, as Completed by Caregivers [ Time Frame: Weeks 1, 13, 25, 37, 49, 57; then every 24 weeks until end of study (up to approximately 152 weeks) ]


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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children less than (<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh <40 kilograms (kg) (Cohort A only); and participants <2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)
  • Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is [i.e.], greater than or equal to [>/=] 5 bethesda units [BU])
  • Requires treatment with bypassing agents
  • Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII
  • Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
  • Other disease that may increase risk of bleeding or thrombosis
  • History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection
  • Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus
  • Use of systemic immunomodulators at enrollment or planned use during the study period
  • Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
  • Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)
  • Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement

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): NCT02795767


  Show 29 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02795767     History of Changes
Other Study ID Numbers: BH29992
2016-000073-21 ( EudraCT Number )
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Antibodies, Bispecific
Coagulants
Immunologic Factors
Physiological Effects of Drugs