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A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Patients With Inhibitors (HAVEN 1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Hoffmann-La Roche
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02622321
First received: December 2, 2015
Last updated: November 4, 2016
Last verified: November 2016
  Purpose
This multicenter, open-label study will evaluate the safety, efficacy and pharmacokinetics of prophylactic emicizumab treatment in patients previously treated with episodic or prophylactic bypassing agents. Episodic bypassing agent patients will be randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) versus no prophylaxis (Arm B) and will be stratified across Arms A and B according to the number of bleeds they experienced over the last 24 weeks prior to study entry (less than [<] 9 or greater than or equal to [>=] 9 bleeds); Arm B patients will have the opportunity to switch to emicizumab prophylaxis after 24 weeks on-study. Prophylactic bypassing agent patients will switch to emicizumab prophylaxis (Arm C) from the start of the trial; enrollment will be extended for 24 weeks after the last patient has enrolled in Arms A or B or until approximately 50 patients have enrolled in Arm C, whichever occurs first. Episodic bypassing agent patients who previously participated in a Non-Interventional Study BH29768 but were unable to enroll in Arms A or B prior to their closure will have the opportunity to enroll in Arm D until 24 weeks after the last patient has enrolled in Arms A or B or until approximately 35 patients have enrolled in Arm D, whichever occurs first. Like patients in Arms A and C, Arm D patients will receive emicizumab prophylaxis from the start of the trial. All patients will continue to receive standard of care/background treatment with their usual episodic bypassing agent therapy to treat breakthrough bleeds, as needed.

Condition Intervention Phase
Hemophilia A
Drug: Emicizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Multi-Center, Open-Label Phase III Clinical Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Patients With Inhibitors (HAVEN 1)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of bleeds over time [ Time Frame: 24 weeks or discontinuation from the study, whichever occurrs first (up to approximately 26 months) ]

Secondary Outcome Measures:
  • Number of all bleeds (whether treated or not treated by coagulation factors) over time [ Time Frame: 24 weeks or discontinuation from the study, whichever occurs first (up to approximately 26 months) ]
  • Reduction in number of all bleeds over time [ Time Frame: Baseline, 24 weeks ]
  • Reduction in number of bleeds over time [ Time Frame: Baseline, 24 weeks ]
  • Reduction in number of joint bleeds over time [ Time Frame: Baseline, 24 weeks ]
  • Reduction in number of target joint bleeds over time [ Time Frame: Baseline, 24 weeks ]
  • Hemophilia-Specific Quality of Life (Haem-A-QoL) (adults) [ Time Frame: Baseline, 24 weeks ]
  • Haemo-QoL-Short Form (adolescents) [ Time Frame: Baseline, 24 weeks ]
  • European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) score [ Time Frame: Baseline, 24 weeks ]
  • Trough plasma concentration (Ctrough) of emicizumab [ Time Frame: (Pre-dose) Every week during Weeks 1-4, every 2 weeks during Weeks 5-8, every 4 weeks during Weeks 9-24, every 8 weeks during Weeks 25-48, every 12 weeks thereafter while on emicizumab until the end of the study (approximately 108 weeks) ]

Estimated Enrollment: 118
Study Start Date: November 2015
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Episodic Treatment+Study Drug (Emicizumab Prophylaxis)
Patients with inhibitors who received episodic treatment with bypassing agents prior to study entry will be randomized to receive emicizumab prophylaxis when they start the trial.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 mg/kg/week for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Active Comparator: Arm B: Episodic Treatment (No Prophylaxis)
Patients with inhibitors who received episodic treatment with bypassing agents prior to study entry will be randomized to continue episodic bypassing agent treatment when they start the trial; they will have the opportunity to switch to emicizumab prophylaxis after 24 weeks on-study.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 mg/kg/week for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Experimental: Arm C: Study Drug (Emicizumab Prophylaxis)+Episodic Treatment
Patients with inhibitors who received prophylactic treatment with bypassing agents prior to study entry will receive emicizumab prophylaxis when they start the trial.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 mg/kg/week for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Experimental: Arm D: Study Drug (Emicizumab Prophylaxis)+Episodic Treatment
Episodic bypassing agent patients who previously participated in a Non-Interventional Study BH29768 but were unable to enroll in Arms A or B prior to their closure will have the opportunity to enroll in Arm D, in which they will receive emicizumab prophylaxis when they start the trial.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 mg/kg/week for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262

  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 12 years or older at the time of informed consent
  • Body weight >=40 kg at the time of screening
  • Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (i.e., >=5 Bethesda Units [BU])
  • Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks
  • >=6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing agent regimen) or >=2 bleeds in the last 24 weeks prior to screening (if on a prophylactic bypassing agent regimen)
  • Adequate hematologic function
  • Adequate hepatic function
  • Adequate renal function
  • For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective contraceptive methods

Exclusion Criteria:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of patients who have received a treatment regimen of FVIII prophylaxis with concurrent bypassing agent prophylaxis
  • Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
  • Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
  • History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
  • Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/microliter within 24 weeks prior to screening
  • Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
  • Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
  • Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
  • Receipt of Emicizumab in 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 within last 30 days or 5 half-lives, whichever is shorter An investigational drug concurrently
  • Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority)
  • Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient
  • Pregnancy or lactation, or intent to become pregnant during the study
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02622321

Contacts
Contact: Reference Study ID Number: BH29884 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 47 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: NCT02622321     History of Changes
Other Study ID Numbers: BH29884
2015-002866-21 ( EudraCT Number )
Study First Received: December 2, 2015
Last Updated: November 4, 2016

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

ClinicalTrials.gov processed this record on March 24, 2017