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A Study of Once-Weekly Emicizumab in Children and Adolescents With Hemophilia A and Factor VIII (FVIII) Inhibitors (HAVEN 2)

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02795767
First Posted: June 10, 2016
Last Update Posted: July 28, 2017
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.
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This single-arm, multicenter, open-label, Phase III clinical study will enroll children (less than [<] 12 years of age) and adolescents (12 to 17 years of age) with hemophilia A and FVIII inhibitors who are currently receiving treatment with bypassing agents. Participants will receive prophylactic treatment with emicizumab as weekly subcutaneous (SC) doses for 52 weeks. All participants will continue to receive episodic treatment for breakthrough bleeds as needed. Breakthrough bleeds should preferably be treated with recombinant factor VIIa (rFVIIa) only at the lowest dose expected to achieve hemostasis and use of activated prothrombin complex concentrate (aPCC) or other bypassing agents (e.g., Byclot®) should be avoided.

Condition Intervention Phase
Hemophilia A Drug: Emicizumab Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once Weekly Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

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

Secondary Outcome Measures:
  • Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Spontaneous Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Joint Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Target Joint Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Reduction From Baseline in Number of Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Reduction From Baseline in Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Reduction From Baseline in Number of Spontaneous Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Reduction From Baseline in Number of Joint Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Reduction From Baseline in Number of Target Joint Bleeds Over Time [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over Time Based on Up-Titration [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Spontaneous Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Joint Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to approximately 52 weeks ]
  • Number of Target Joint Bleeds Over Time Based on Up-Titration [ Time Frame: Baseline up to approximately 52 weeks ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: From Baseline up to approximately 104 weeks ]
  • Percentage of Participants With Anti-Emicizumab Antibodies [ Time Frame: Predose (hour 0) at Weeks 1, 5, 17, 33, 49, every 12 weeks starting from week 57, study completion/early termination and at the 24-week safety follow-up visit (up to approximately 104 weeks) ]
  • Plasma Trough Concentration (Ctrough) of Emicizumab [ Time Frame: Pre-dose (hour 0) in 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 104 weeks) ]
  • Change From Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline, 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 104 weeks) ]
  • Change From Baseline in Factor VIII (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 104 weeks) ]
  • Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Score, as Completed by Participants 8 to 17 Years of Age [ Time Frame: Baseline, Weeks 13, 25, 37, 49, 57; then every 24 weeks until end of study (up to approximately 104 weeks) ]
  • 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: Baseline, Weeks 13, 25, 37, 49, 57; then every 24 weeks until end of study (up to approximately 104 weeks) ]

Enrollment: 60
Actual Study Start Date: July 22, 2016
Estimated Study Completion Date: July 31, 2018
Estimated Primary Completion Date: April 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hemophilia A and FVIII Inhibitors
Participants with inhibitors who received episodic or prophylactic treatment with bypassing agents prior to study entry will receive emicizumab prophylaxis on Day 1 of each week after initiating the trial.
Drug: Emicizumab
Emicizumab will be administered SC weekly dose at 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks, followed by 1.5 mg/kg/week up to 52 weeks. From 12 weeks onwards, the dose can be increased from 1.5 to 2.25 mg/kg/week or from 2.25 to 3.0 mg/kg/week if the participant has developed >/=2 bleeds in 12 weeks from Week 5 or 9, respectively.
Other Name: RO5534262

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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) and participants <2 years of age after protocol-defined interim data review criteria are met
  • Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is, 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
  • Hypersensitivity to monoclonal antibodies or components of the emicizumab injection
  • Known human immunodeficiency virus (HIV) or hepatitis B or C
  • Use of systemic immunomodulators
  • Planned surgery during study (excluding minor procedures such as tooth extraction or incision and drainage)
  • 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
  Contacts and Locations
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 27 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02795767     History of Changes
Other Study ID Numbers: BH29992
2016-000073-21 ( EudraCT Number )
First Submitted: June 7, 2016
First Posted: June 10, 2016
Last Update Posted: July 28, 2017
Last Verified: July 2017

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
Coagulants


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