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A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks in Participants With Hemophilia A (HAVEN 4)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03020160
First Posted: January 13, 2017
Last Update Posted: September 29, 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 multicenter, open-label, non-randomized study will assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab administered at a dose of 6 milligrams per kilogram (mg/kg) every 4 weeks in participants with hemophilia A with or without inhibitors against factor VIII (FVIII). The study consists of 2 parts: a pharmacokinetic (PK) run-in part followed by an expansion part.

Condition Intervention Phase
Hemophilia A Drug: Emicizumab Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Open-Label, Phase III Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks (Q4W) in Patients With Hemophilia A

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Expansion Part: Number of Bleeding Events Over Time [ Time Frame: Expansion Part: Day 1 up to study completion (a minimum of 24 weeks, up to approximately 20 months) ]

Secondary Outcome Measures:
  • Expansion Part: Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed Using Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Score [ Time Frame: Expansion Part: Baseline, Weeks 13 and 25, thereafter every 12 weeks up to study completion/ early termination (up to approximately 20 months) ]
  • Expansion Part: Change from Baseline in HRQoL as Assessed Using Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Score [ Time Frame: Expansion Part: Baseline, Weeks 13 and 25, thereafter every 12 weeks up to study completion/ early termination (up to approximately 20 months) ]
  • Expansion Part: Participant Preference for Treatment as Assessed Using Preference Survey Score [ Time Frame: Expansion Part: Predose (0 hour [hr]) at Week 17 ]
  • Expansion Part: Change from Baseline in Health Status as Assessed Using European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaires Score [ Time Frame: Expansion Part: Baseline, Weeks 13 and 25, thereafter every 12 weeks up to study completion/ early termination (up to approximately 20 months) ]
  • Expansion Part: Number of Days Away From School/Work [ Time Frame: Expansion Part: Baseline, Weeks 13 and 25, thereafter every 12 weeks up to study completion/ early termination (up to approximately 20 months) ]
  • Expansion Part: Number of Days Hospitalized [ Time Frame: Expansion Part: Baseline, Weeks 13 and 25, thereafter every 12 weeks up to study completion/ early termination (up to approximately 20 months) ]
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 24 weeks after last dose of study treatment (up to approximately 20 months) ]
  • Number of Participants With Anti-drug Antibodies (ADA) to Emicizumab [ Time Frame: Baseline up to 24 weeks after last dose of study treatment (up to approximately 20 months) ]
  • Number of Participants With Anti-FVIII Antibodies [ Time Frame: Baseline up to 24 weeks after last dose of study treatment (up to approximately 20 months) ]
  • PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose (0 hr) and 8 hrs post-dose on Day [D]1; D3,5,8,11,15,18,22,25,29 (pre-dose),36,43,50,57,85,113,141,148,155,162,169, once between 2 drug intakes from Week 9-21, early discontinuation and safety follow-up (up to approx. 20 months) ]
  • PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose and 8 hrs post-dose on D1; D3,5,8,11,15,18,22,25,29 (pre-dose),36,43,50,57,85,113,141,148,155,162,169, between 2 drug intakes from Week 9-21, early discontinuation and safety follow-up (up to approximately 20 months) ]
  • PK Run-In Part: Area Under the Plasma Concentration-time Curve From Time Zero to end of Dosing Interval (AUC[0-tau]) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose and 8 hrs post-dose on D1; D3, 5, 8, 11, 15, 18, 22, 25, 29 (pre-dose) ]
  • PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose and 8 hrs post-dose on D1; D3,5,8,11,15,18,22,25,29 (pre-dose),36,43,50,57,85,113,141,148,155,162,169, once between 2 drug intakes from Week 9-21, early discontinuation and safety follow-up (up to approximately 20 months) ]
  • PK Run-In Part: Apparent Plasma Terminal Half-life (t1/2) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose and 8 hrs post-dose on D1; D3,5,8,11,15,18,22,25,29 (pre-dose),36,43,50,57,85,113,141,148,155,162,169, once between 2 drug intakes from Week 9-21, early discontinuation and safety follow-up (up to approximately 20 months) ]
  • PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab [ Time Frame: PK Run-In Part: Pre-dose and 8 hrs post-dose on D1; D3,5,8,11,15,18,22,25,29 (pre-dose),36,43,50,57,85,113,141,148,155,162,169, once between 2 drug intakes from Week 9-21, early discontinuation and safety follow-up (up to approximately 20 months) ]
  • Expansion Part: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) of Emicizumab [ Time Frame: Expansion Part: Pre-dose (0 hr) at Weeks 1,2,3,4,5,9,13,17,21,25, additionally at early discontinuation and safety follow-up (up to approximately 20 months) ]

Enrollment: 48
Actual Study Start Date: January 30, 2017
Estimated Study Completion Date: July 4, 2018
Estimated Primary Completion Date: July 4, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Emicizumab: Expansion Part
Participants will received SC emicizumab at a loading dose of 3 mg/kg every week for initial 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks for a minimum of 24 weeks.
Drug: Emicizumab
Emicizumab will be administered according to dose and schedule described in respective arms.
Other Name: RO5534262
Experimental: Emicizumab: PK Run-in Part
Participants will received SC emicizumab at a dose of 6 mg/kg every 4 weeks for a minimum of 24 weeks.
Drug: Emicizumab
Emicizumab will be administered according to dose and schedule described in respective arms.
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:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body weight greater than or equal to (>/=) 40 kilograms (kg) at screening
  • Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors
  • Participants using rFVIIa or willing to switch to recombinant activated factor VII (rFVIIa) as primary bypassing agent for the treatment of breakthrough bleeds
  • FVIII inhibitor test during screening with titer results available prior to first administration of study drug
  • Participants without FVIII inhibitors, that is with less than (<) 0.6 Bethesda unit per milliliter [BU/mL];< 1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL, who completed successful immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) indicated by detection of an inhibitor greater than (>) 0.6 BU/mL (> 1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) since ITI
  • Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Ongoing or planned ITI therapy; participants in whom ITI has failed will be eligible with a 72-hour washout period prior to the first emicizumab administration
  • History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator's judgment
  • Participants who are at high risk for thrombotic microangiopathy (TMA) (for example, have a previous medical or family history of TMA), in the investigator's judgment
  • Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
  • Other conditions (for example, certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis
  • History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
  • Known HIV infection with cluster of differentiation (CD) 4 cells counts <200 cells per microliter (cells/mcL)
  • Use of systemic immunomodulators (for example, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
  • Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant
  • Pregnancy or lactation or intention to become pregnant during the study
  • Women with a positive serum pregnancy test result within 7 days prior to initiation of study drug
  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): NCT03020160


Locations
United States, California
University of California Davis
Sacramento, California, United States, 95817
United States, Indiana
Indiana Hemophilia & Thrombosis center
Indianapolis, Indiana, United States, 46260
United States, Michigan
University of Michigan, C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Univ of N Carolina Chapel Hill; Hematology/Oncology
Chapel Hill, North Carolina, United States, 27514
Australia, Queensland
Royal Brisbane Hospital; Clinical Haematology
Brisbane, Queensland, Australia, 4029
Australia, South Australia
Royal Adelaide Hospital; Haematology Clinical Trials
Adelaide, South Australia, Australia, 5000
Belgium
Cliniques Universitaires St-Luc
Bruxelles, Belgium, 1200
UZ Leuven Gasthuisberg
Leuven, Belgium, 3000
Japan
Hokkaido University Hospital
Hokkaido, Japan, 060-8648
Nara Medical University Hospital
Nara, Japan, 634-8522
National Center for Child Health and Development
Tokyo, Japan, 157-8535
Tokyo Medical University Hospital
Tokyo, Japan, 160-0023
Poland
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
Warsaw, Poland, 02-776
SPSK Nr 1, Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
Wrocław, Poland, 50-367
Spain
Hospital Universitario la Paz; Servicio de Hematologia
Madrid, Spain, 28046
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
Sevilla, Spain, 41013
Hospital Universitario la Fe; Servicio de Hematologia
Valencia, Spain, 46026
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: NCT03020160     History of Changes
Other Study ID Numbers: BO39182
2016-001094-33 ( EudraCT Number )
First Submitted: December 21, 2016
First Posted: January 13, 2017
Last Update Posted: September 29, 2017
Last Verified: September 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
Antibodies, Bispecific
Coagulants
Immunologic Factors
Physiological Effects of Drugs