Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors (HAVEN 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02622321
First received: December 2, 2015
Last updated: April 21, 2017
Last verified: April 2017
  Purpose
This multicenter, open-label study will evaluate the safety, efficacy and pharmacokinetics of prophylactic emicizumab treatment in participants previously treated with episodic or prophylactic bypassing agents. Episodic bypassing agent participants 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 participants will have the opportunity to switch to emicizumab prophylaxis after 24 weeks on-study. Prophylactic bypassing agent participants will switch to emicizumab prophylaxis (Arm C) from the start of the trial; enrollment will be extended for 24 weeks after the last participant has enrolled in Arms A or B or until approximately 50 participants have enrolled in Arm C, whichever occurs first. Episodic bypassing agent participants who previously participated in the non-interventional study BH29768 (NCT02476942) or prophylactic bypassing agent participants who were unable to enroll in Arms A, B, or C prior to their closure will have the opportunity to enroll in Arm D. Like participants in Arms A and C, Arm D participants will receive emicizumab prophylaxis from the start of the trial. All participants will continue to receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with rFVIIa at the lowest expected dose to achieve hemostasis.

Condition Intervention Phase
Hemophilia A
Drug: Emicizumab
Drug: rFVIIa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Arms A and B: Number of Bleeds Over Time [ Time Frame: Baseline up to 24 weeks or discontinuation from the study, whichever occurs first ]

Secondary Outcome Measures:
  • Arm A and B: Reduction in Number of All Bleeds (Whether Treated or not Treated by Coagulation Factors) From Baseline to 24 Weeks [ Time Frame: Baseline, 24 weeks ]
  • Arm A and B: Reduction in Number of Spontaneous Bleeds From Baseline to 24 Weeks [ Time Frame: Baseline, 24 weeks ]
  • Arm A and B: Reduction in Number of Joint Bleeds From Baseline to 24 Weeks [ Time Frame: Baseline, 24 weeks ]
  • Arm A and B: Reduction in Number of Target Joint Bleeds From Baseline to 24 Weeks [ Time Frame: Baseline, 24 weeks ]
  • Arm A and B: Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Score in Adult (>/= 18 years of age) Participants [ Time Frame: 24 weeks ]
  • Arm A and B: Haemo-QoL-Short Form (SF) Questionnaire Score in Adolescent (12 to 17 years of age) Participants [ Time Frame: 24 weeks ]
  • Arm A and B: European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score [ Time Frame: 24 weeks ]
  • Arms A and C: Reduction in Number of All Bleeds (Whether Treated or not Treated by Coagulation Factors) From Pre-study to 24 Weeks [ Time Frame: Up to 52 weeks before study entry (will be assessed retrospectively at baseline), 24 weeks ]
  • Arms A and C: Reduction in Number of Treated Bleeds From Pre-study to 24 Weeks [ Time Frame: Up to 52 weeks before study entry (will be assessed retrospectively at baseline), 24 weeks ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approxiamtely 26 months ]
  • Percentage of Participants With Anti- Emicizumab Antibodies [ Time Frame: Baseline up to approximately 26 months ]
  • Trough Plasma Concentration (Ctrough) of emicizumab [ Time Frame: Pre-dose (Hour 0) 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 26 months) ]

Enrollment: 113
Actual Study Start Date: November 18, 2015
Estimated Study Completion Date: July 31, 2018
Primary Completion Date: October 25, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Episodic Treatment): Emicizumab
Participants who received episodic treatment with bypassing agents prior to study entry will be randomized to receive prophylactic emicizumab. Participants will continue to receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with recombinant activated factor VII (rFVIIa) at the lowest expected dose to achieve hemostasis.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Drug: rFVIIa
In case of a breakthrough bleed, participants will receive a bypassing agent, preferably rFVIIa, at the lowest expected dose to achieve hemostasis (no more than 90 micrograms per kilogram as an initial dose).
Other Name: NovoSeven®
Active Comparator: Arm B (Episodic Treatment): No Emicizumab
Participants who received episodic treatment with bypassing agents prior to study entry will be randomized to not receive prophylaxis. These participants will have the opportunity to switch to emicizumab prophylaxis after 24 weeks on-study. Participants will continue to receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with rFVIIa at the lowest expected dose to achieve hemostasis.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Drug: rFVIIa
In case of a breakthrough bleed, participants will receive a bypassing agent, preferably rFVIIa, at the lowest expected dose to achieve hemostasis (no more than 90 micrograms per kilogram as an initial dose).
Other Name: NovoSeven®
Experimental: Arm C (Prophylactic Treatment): Emicizumab
Participants on prophylactic bypassing agents prior to study entry will be enrolled to receive prophylactic emicizumab. Participants may receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with rFVIIa at the lowest expected dose to achieve hemostasis.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Drug: rFVIIa
In case of a breakthrough bleed, participants will receive a bypassing agent, preferably rFVIIa, at the lowest expected dose to achieve hemostasis (no more than 90 micrograms per kilogram as an initial dose).
Other Name: NovoSeven®
Experimental: Arm D (Episodic or Prophylactic Treatment): Emicizumab
Participants on episodic bypassing agents prior to study entry, who participated in Study BH29768 but were unable to enroll in Arms A or B, or participants on prophylactic bypassing agents who were unable to enroll in Arm C, will be enrolled in this arm to receive prophylactic emicizumab. Participants will continue to receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with rFVIIa at the lowest expected dose to achieve hemostasis.
Drug: Emicizumab
Emicizumab will be administered subcutaneously at a dose of 3 milligrams per kilogram per week (mg/kg/week) for 4 weeks followed by 1.5 mg/kg/week up to the end of the study.
Other Name: ACE910; RO5534262
Drug: rFVIIa
In case of a breakthrough bleed, participants will receive a bypassing agent, preferably rFVIIa, at the lowest expected dose to achieve hemostasis (no more than 90 micrograms per kilogram as an initial dose).
Other Name: NovoSeven®

  Eligibility

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

Inclusion Criteria:

  • Body weight >/= 40 kg at the time of screening
  • Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor ( that is [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, hepatic and 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:

  • Participants with inherited or acquired bleeding disorder other than hemophilia A
  • Participants with ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of participants 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
  • Participants with other conditions (example [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 cluster of differentiation 4 (CD4) count < 200 cells/microliter within 24 weeks prior to screening
  • Use of systemic immunomodulators (e.g., interferon or rituximab) at enrolment or planned use during the study, with the exception of antiretroviral therapy
  • 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 judgment
  • 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 participant'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 participant
  • 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

  Show 46 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: April 21, 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

ClinicalTrials.gov processed this record on April 26, 2017