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Efficacy, Safety, and Pharmacokinetic Study of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Participants (HAVEN 5)

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ClinicalTrials.gov Identifier: NCT03315455
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : January 14, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This randomized, multicenter, open-label, Phase 3 study is designed to investigate the efficacy, safety, and pharmacokinetics of emicizumab in participants with hemophilia A regardless of factor VIII (FVIII) inhibitor status. Participants who received episodic therapy with FVIII or bypassing agents prior to study entry and experienced at least 5 bleeds over the prior 24 weeks will be randomized in a 2:2:1 ratio to the following regimens: 1) Emicizumab prophylaxis at 3 milligrams per kilogram (mg/kg) every week (QW) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg QW SC; 2) Emicizumab prophylaxis at 3 mg/kg QW SC for 4 weeks, followed by 6 mg/kg every 4 weeks (Q4W) SC; 3) No prophylaxis (control arm).

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : September 3, 2019
Estimated Study Completion Date : January 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
Experimental: Prophylactic Emicizumab 1.5 mg/kg QW
Participants will receive prophylactic emicizumab at a dose of 3 mg/kg via SC injection QW for first 4 weeks, followed by 1.5 mg/kg via SC injection QW up to 24 weeks. After 24 weeks treatment, participants will be allowed to continue emicizumab until marketing authorization as part of this study or a separate extension study.
Drug: Emicizumab
Emicizumab will be administered via SC injection.
Other Name: RO5534262

Experimental: Prophylactic Emicizumab 6 mg/kg Q4W
Participants will receive prophylactic emicizumab at a dose of 3 mg/kg via SC injection QW for first 4 weeks, followed by 6 mg/kg via SC injection Q4W (or 3 mg/kg Q2W if Q4W is not to be pursued) up to 24 weeks. After 24 weeks treatment, participants will be allowed to continue emicizumab until marketing authorization as part of this study or a separate extension study.
Drug: Emicizumab
Emicizumab will be administered via SC injection.
Other Name: RO5534262

Control Arm: No Prophylaxis
Participants will not receive any prophylactic treatment up to 24 weeks. After 24 weeks, participants will have the opportunity to switch to receive emicizumab prophylaxis at 3 mg/kg QW via SC injection for 4 weeks, followed by 6 mg/kg Q4W (or 3 mg/kg Q2W if Q4W is not to be pursued), until marketing authorization as part of this study or a separate extension study.
Drug: Emicizumab
Emicizumab will be administered via SC injection.
Other Name: RO5534262




Primary Outcome Measures :
  1. Numbers of Treated Bleeds Over Time [ Time Frame: From Baseline up to 24 weeks ]

Secondary Outcome Measures :
  1. Reduction from Baseline in Number of All Bleeds (Whether Treated or Not Treated With Coagulation Factors) Over 24 Weeks [ Time Frame: From Baseline up to 24 weeks ]
  2. Reduction From Pre-Study in Number of Treated Bleeds Over 24 Weeks [ Time Frame: Up to 24 weeks before study entry (will be assessed retrospectively at baseline), 24 weeks ]
  3. Reduction From Pre-Study in Number of All Bleeds (Whether Treated or not Treated by Coagulation Factors) Over 24 Weeks [ Time Frame: Up to 24 weeks before study entry (will be assessed retrospectively at baseline), 24 weeks ]
  4. Reduction From Baseline in Number of Spontaneous Bleeds Over 24 Weeks [ Time Frame: From Baseline up to 24 weeks ]
  5. Reduction from Baseline in Number of Joint Bleeds Over 24 Weeks [ Time Frame: From Baseline up to 24 weeks ]
  6. Reduction from Baseline in Number of Target Joint Bleeds Over 24 Weeks [ Time Frame: From Baseline up to 24 weeks ]
  7. Change from Baseline in Hemophilia A Quality of Life (Haemo-A-QoL) Questionnaire Score in Participants Greater Than or Equal to (>/=) 18 Years of Age at Week 24 [ Time Frame: Baseline, Week 24 ]
  8. Change from Baseline in Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Score in Participants 12 to 17 Years of Age at Week 24 [ Time Frame: Baseline, Week 24 ]
  9. Change from Baseline in European Quality of Life 5-Dimensions-5 Levels Questionnaire (EQ-5D-5L) Score at Week 24 [ Time Frame: Baseline, Week 24 ]
  10. Percentage of Participants with Adverse Events (AEs) [ Time Frame: From Baseline up to end of study (overall approximately 22 months) ]
  11. Percentage of Participants with Anti-Emicizumab Antibodies [ Time Frame: From Baseline up to end of study (overall approximately 22 months) ]
  12. Plasma Trough Concentration (Ctrough) of Emicizumab [ Time Frame: QW: predose (0 hours) on Weeks (Wk) 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 33, 41, 49, every 12 Wk until end of study (EOS); Q4W: 0 hours on Wk 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, every 12 Wk until EOS (EOS: approximately 22 months) ]


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

Inclusion Criteria:

  • Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors
  • Body weight greater than or equal to (>/=) 40 kilograms at the time of screening
  • Participants without FVIII inhibitors (< 0.6 Bethesda unit per milliliter [BU/mL]) who completed successful immune tolerance induction (ITI) must have done so at least 5 years before screening and have no evidence of inhibitor recurrence (permanent or temporary)
  • Documentation of the details of episodic therapy (FVIII or bypassing agents) and of number of bleeding episodes for at least the last 24 weeks and >/=5 bleeds in the last 24 weeks prior to study entry
  • Adequate hematologic, hepatic, and renal function
  • For women of child bearing potential: agreement to remain abstinent or use a protocol defined contraceptive measures during the treatment period and for at least 5 elimination half-lives (24 weeks) after the last dose of study drug

Exclusion Criteria:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Participants who are at high risk for thrombotic microangiopathy, in the investigator's judgment
  • History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator's judgment
  • Previous (in the past 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 that may increase risk of bleeding or thrombosis
  • History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
  • Known human immuno-deficiency virus (HIV) infection with cluster of differentiation (CD)4 count <200 cells/microliter (cells/mcL) within 24 weeks prior to screening. Participants with HIV infection who has CD4 >200 cells/mcL and meet all other criteria are eligible
  • Use of systemic immunomodulators at enrollment or planned use during the study, with the exception of anti-retroviral therapy
  • Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study
  • 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 concurrently, within last 30 days or 5 half-lives, whichever is shorter
  • Pregnant or lactating, or intending to become pregnant during the study
  • Women with positive serum pregnancy test result within 7 days prior to initiation of study drug

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): NCT03315455


Contacts
Contact: Reference Study ID Number: YO39309 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
China
Anhui Provincial Hospital Not yet recruiting
Anhui, China, 230001
Peking Union Medical College Hospital Active, not recruiting
Beijing City, China, 100032
Beijing Children's Hospital, Capital Medical University; rheumatism Recruiting
Beijing City, China, 100045
Xiangya Hospital of Centre-South University Recruiting
Changsha, China, 410008
Southern Medical University Nanfang Hospital Active, not recruiting
Guangzhou City, China, 510515
Ruijin Hospital Shanghai Jiaotong University School of Medicine; hemotology Recruiting
Shanghai City, China, 200025
Children's Hospital of Shenzhen Not yet recruiting
Shenzhen, China
Tianjin Institute of Hematology & Blood Diseases Hospital Active, not recruiting
Tianjin, China, 300020
Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology Recruiting
Wuhan, China, 430022
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech Recruiting
Wuhan, China, 430030
Hong Kong
Queen Mary Hospital; Department of Pediatrics & Adolescent Medicine Active, not recruiting
Hong kong, Hong Kong
Prince of Wales Hospital; Department of Pediatrics Active, not recruiting
Shatin, Hong Kong
Malaysia
Penang General Hospital; Department of Medicine Active, not recruiting
Pulau Pinang, Penang, Malaysia, 10450
Queen Elizabeth Hospital Active, not recruiting
Sabah, Malaysia, 88586
Thailand
Ramathibodi Hospital Recruiting
Bangkok, Thailand, 10400
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03315455     History of Changes
Other Study ID Numbers: YO39309
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: January 14, 2019
Last Verified: January 2019

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

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