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

Primary Purpose

Hemophilia A

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Emicizumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Inclusion Criteria for Arms A, B, and C:

  • Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors
  • Aged 12 years or older at the time of informed consent
  • Body weight ≥40 kilograms (kg) 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 measure during the treatment period and for at least 5 elimination half-lives (24 weeks) after the last dose of study drug

Inclusion Criteria for Arm D:

  • Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (i.e., ≥5 BU/mL)
  • Children <12 years old at time of informed consent
  • Body weight >3 kg at time of informed consent
  • Requires treatment with bypassing agents
  • Adequate hematologic, hepatic, and renal function
  • For female participants who are of childbearing potential, follow the same contraception criteria as listed above for Arms A, B, and C

Exclusion Criteria:

Exclusion Criteria for Arms A, B, and C:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • 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 4 (CD4) count <200 cells/microliter (cells/mcL) within 24 weeks prior to screening. Participants with HIV infection who have 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

Exclusion Criteria for Arm D:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Ongoing (or plan to receive during the study) ITI therapy or prophylaxis treatment with FVIII
  • 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 diseases 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 infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
  • At high risk for thrombotic microangiopathy, in the investigator's judgment
  • Use of systemic immunomodulators at enrollment or planned use during the study
  • Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
  • Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)
  • 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
  • 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
  • Pregnant or lactating, or intending to become pregnant during the study

Sites / Locations

  • Peking Union Medical College Hospital
  • Beijing Children's Hospital, Capital Medical University; rheumatism
  • Xiangya Hospital of Centre-South University
  • Southern Medical University Nanfang Hospital
  • Ruijin Hospital Shanghai Jiaotong University School of Medicine; hemotology
  • Tianjin Institute of Hematology & Blood Diseases Hospital
  • Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
  • Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
  • Queen Mary Hospital; Department of Pediatrics & Adolescent Medicine
  • Prince of Wales Hospital; Department of Pediatrics
  • Penang General Hospital; Department of Medicine
  • Queen Elizabeth Hospital
  • Ramathibodi Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Other

Experimental

Arm Label

Arm A: Emicizumab Prophylaxis at 1.5 mg/kg QW

Arm B: Emicizumab Prophylaxis at 6 mg/kg Q4W

Arm C: No Prophylaxis (Control Arm)

Arm D: Emicizumab Prophylaxis at 1.5 mg/kg QW

Arm Description

Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm A 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.

Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm B 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.

Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm C will not receive any prophylactic treatment for at least 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 until marketing authorization as part of this study or a separate extension study, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.

Participants <12 years old with hemophilia A and FVIII inhibitors who are enrolled to Arm D 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.

Outcomes

Primary Outcome Measures

Model-Based Annualized Bleeding Rate for Treated Bleeds
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Mean Calculated Annualized Bleeding Rate for Treated Bleeds

Secondary Outcome Measures

Model-Based Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Median Calculated Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Mean Calculated Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Model-Based Annualized Bleeding Rate for Spontaneous Bleeds
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Median Calculated Annualized Bleeding Rate for Spontaneous Bleeds
Mean Calculated Annualized Bleeding Rate for Spontaneous Bleeds
Model-Based Annualized Bleeding Rate for Joint Bleeds
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Median Calculated Annualized Bleeding Rate for Joint Bleeds
Mean Calculated Annualized Bleeding Rate for Joint Bleeds
Model-Based Annualized Bleeding Rate for Target Joint Bleeds
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Median Calculated Annualized Bleeding Rate for Target Joint Bleeds
Mean Calculated Annualized Bleeding Rate for Target Joint Bleeds
Intra-Participant Comparison of the Model-Based Annualized Bleeding Rate (ABR) for Treated Bleeds on Study Versus Pre-Study
Intra-Participant Comparison of the Model-Based ABR for All Bleeds (Whether Treated or not Treated by Coagulation Factors) on Study Versus Pre-Study
Arms A, B, and C: Change from Baseline in Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score in Participants ≥18 Years of Age at Week 25
Arms A, B, and C: Change from Baseline in Haem-A-QoL Questionnaire Physical Health Domain Score in Participants ≥18 Years of Age at Week 25
Arms A, B, and C: Change from Baseline in Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score in Participants 12 to 17 Years of Age at Week 25
Arms A, B, and C: Change from Baseline in European Quality of Life 5-Dimensions-5 Levels Questionnaire (EQ-5D-5L) Index Utility Score at Week 25
Arms A, B, and C: Change from Baseline in EQ-5D-5L Questionnaire Visual Analog Scale (VAS) Score at Week 25
Arm D: Change from Baseline in Haemo-QoL-SF Questionnaire Score in Participants 8 to 12 Years of Age at Week 25
Arm D: Change from Baseline in the Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors (Adapted Inhib-QoL) Including Aspects of Caregiver Burden Questionnaire Score Over Time
Number of Participants with Adverse Events by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale
Number of Participants with Adverse Events Leading to Study Drug Discontinuation
Number of Participants with Thromboembolic Events by Severity, According to the WHO Toxicity Grading Scale
Number of Participants with Thrombotic Microangiopathy by Severity, According to the WHO Toxicity Grading Scale
Number of Participants with Injection-Site Reactions by Severity, According to the WHO Toxicity Grading Scale
Number of Participants with Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions
Number of Participants with Serum Chemistry Laboratory Abnormalities by Highest WHO Grade Post-Baseline, According to the WHO Toxicity Grading Scale
Number of Participants with Hematology Laboratory Abnormalities by Highest WHO Grade Post-Baseline, According to the WHO Toxicity Grading Scale
Change from Baseline in Body Temperature Over Time
Change from Baseline in Pulse Rate Over Time
Change from Baseline in Respiratory Rate Over Time
Change from Baseline in Systolic Blood Pressure Over Time
Change from Baseline in Diastolic Blood Pressure Over Time
Number of Participants with Anti-Emicizumab Antibodies
Plasma Trough Concentration (Ctrough) of Emicizumab

Full Information

First Posted
October 17, 2017
Last Updated
February 13, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT03315455
Brief Title
Efficacy, Safety, and Pharmacokinetic Study of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Participants
Acronym
HAVEN 5
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 26, 2018 (Actual)
Primary Completion Date
August 3, 2022 (Actual)
Study Completion Date
May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

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

5. Study Description

Brief Summary
This multicenter, open-label, Phase 3 study with randomized and non-randomized arms is designed to investigate the efficacy, safety, and pharmacokinetics of emicizumab in participants with hemophilia A regardless of factor VIII (FVIII) inhibitor status. Participants greater than or equal to (≥)12 years old 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: Arm A: Emicizumab prophylaxis at 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg QW SC; Arm B: Emicizumab prophylaxis at 3 mg/kg QW SC for 4 weeks, followed by 6 mg/kg once every 4 weeks (Q4W) SC; and Arm C: No prophylaxis (control arm). In addition, pediatric participants less than (<)12 years old with hemophilia A and FVIII inhibitors who received episodic therapy with bypassing agents prior to study entry will be enrolled to Arm D: Emicizumab prophylaxis at 3 mg/kg QW SC for 4 weeks, followed by 1.5 mg/kg QW SC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Emicizumab Prophylaxis at 1.5 mg/kg QW
Arm Type
Experimental
Arm Description
Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm A 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.
Arm Title
Arm B: Emicizumab Prophylaxis at 6 mg/kg Q4W
Arm Type
Experimental
Arm Description
Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm B 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.
Arm Title
Arm C: No Prophylaxis (Control Arm)
Arm Type
Other
Arm Description
Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm C will not receive any prophylactic treatment for at least 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 until marketing authorization as part of this study or a separate extension study, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.
Arm Title
Arm D: Emicizumab Prophylaxis at 1.5 mg/kg QW
Arm Type
Experimental
Arm Description
Participants <12 years old with hemophilia A and FVIII inhibitors who are enrolled to Arm D 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 for at least 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, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.
Intervention Type
Drug
Intervention Name(s)
Emicizumab
Other Intervention Name(s)
Hemlibra, RO5534262, RG6013, ACE910
Intervention Description
Emicizumab will be administered via subcutaneous (SC) injection, as described for each treatment arm.
Primary Outcome Measure Information:
Title
Model-Based Annualized Bleeding Rate for Treated Bleeds
Description
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Time Frame
From Baseline to at least 24 weeks
Title
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Mean Calculated Annualized Bleeding Rate for Treated Bleeds
Time Frame
From Baseline to at least 24 weeks
Secondary Outcome Measure Information:
Title
Model-Based Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Description
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Time Frame
From Baseline to at least 24 weeks
Title
Median Calculated Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Time Frame
From Baseline to at least 24 weeks
Title
Mean Calculated Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Time Frame
From Baseline to at least 24 weeks
Title
Model-Based Annualized Bleeding Rate for Spontaneous Bleeds
Description
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Time Frame
From Baseline to at least 24 weeks
Title
Median Calculated Annualized Bleeding Rate for Spontaneous Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Mean Calculated Annualized Bleeding Rate for Spontaneous Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Model-Based Annualized Bleeding Rate for Joint Bleeds
Description
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Time Frame
From Baseline to at least 24 weeks
Title
Median Calculated Annualized Bleeding Rate for Joint Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Mean Calculated Annualized Bleeding Rate for Joint Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Model-Based Annualized Bleeding Rate for Target Joint Bleeds
Description
The model-based annualized bleeding rate (ABR) will be estimated using a negative binomial regression model.
Time Frame
From Baseline to at least 24 weeks
Title
Median Calculated Annualized Bleeding Rate for Target Joint Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Mean Calculated Annualized Bleeding Rate for Target Joint Bleeds
Time Frame
From Baseline to at least 24 weeks
Title
Intra-Participant Comparison of the Model-Based Annualized Bleeding Rate (ABR) for Treated Bleeds on Study Versus Pre-Study
Time Frame
Up to 24 weeks before study entry (will be assessed retrospectively at Baseline), from Baseline to at least 24 weeks on study
Title
Intra-Participant Comparison of the Model-Based ABR for All Bleeds (Whether Treated or not Treated by Coagulation Factors) on Study Versus Pre-Study
Time Frame
Up to 24 weeks before study entry (will be assessed retrospectively at Baseline), from Baseline to at least 24 weeks on study
Title
Arms A, B, and C: Change from Baseline in Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score in Participants ≥18 Years of Age at Week 25
Time Frame
Baseline and Week 25
Title
Arms A, B, and C: Change from Baseline in Haem-A-QoL Questionnaire Physical Health Domain Score in Participants ≥18 Years of Age at Week 25
Time Frame
Baseline and Week 25
Title
Arms A, B, and C: Change from Baseline in Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score in Participants 12 to 17 Years of Age at Week 25
Time Frame
Baseline and Week 25
Title
Arms A, B, and C: Change from Baseline in European Quality of Life 5-Dimensions-5 Levels Questionnaire (EQ-5D-5L) Index Utility Score at Week 25
Time Frame
Baseline and Week 25
Title
Arms A, B, and C: Change from Baseline in EQ-5D-5L Questionnaire Visual Analog Scale (VAS) Score at Week 25
Time Frame
Baseline and Week 25
Title
Arm D: Change from Baseline in Haemo-QoL-SF Questionnaire Score in Participants 8 to 12 Years of Age at Week 25
Time Frame
Baseline and Week 25
Title
Arm D: Change from Baseline in the Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors (Adapted Inhib-QoL) Including Aspects of Caregiver Burden Questionnaire Score Over Time
Time Frame
Baseline (Week 1) and Weeks 17, 29, 37, and 49, every 12 weeks during extension phase, and study completion (up to 48 months)
Title
Number of Participants with Adverse Events by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Adverse Events Leading to Study Drug Discontinuation
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Thromboembolic Events by Severity, According to the WHO Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Thrombotic Microangiopathy by Severity, According to the WHO Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Injection-Site Reactions by Severity, According to the WHO Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Severe Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Serum Chemistry Laboratory Abnormalities by Highest WHO Grade Post-Baseline, According to the WHO Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Number of Participants with Hematology Laboratory Abnormalities by Highest WHO Grade Post-Baseline, According to the WHO Toxicity Grading Scale
Time Frame
From Baseline until end of study (up to 85 months)
Title
Change from Baseline in Body Temperature Over Time
Time Frame
Baseline, Weeks 1, 25, and 49, and at study completion (up to 85 months)
Title
Change from Baseline in Pulse Rate Over Time
Time Frame
Baseline, Weeks 1, 25, and 49, and at study completion (up to 85 months)
Title
Change from Baseline in Respiratory Rate Over Time
Time Frame
Baseline, Weeks 1, 25, and 49, and at study completion (up to 85 months)
Title
Change from Baseline in Systolic Blood Pressure Over Time
Time Frame
Baseline, Weeks 1, 25, and 49, and at study completion (up to 85 months)
Title
Change from Baseline in Diastolic Blood Pressure Over Time
Time Frame
Baseline, Weeks 1, 25, and 49, and at study completion (up to 85 months)
Title
Number of Participants with Anti-Emicizumab Antibodies
Time Frame
QW: Pre-dose at Weeks 1, 5, 9, 13, 17, 21, 25, 33, 41, 49, and every 12 weeks thereafter until study completion; Q4W: Pre-dose at Weeks 1, 5, 9, 13, 17, 21, 25, and every 12 weeks thereafter until study completion (up to 42 months)
Title
Plasma Trough Concentration (Ctrough) of Emicizumab
Time Frame
QW: Predose at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 33, 41, 49, and every 12 weeks thereafter to study completion; Q4W: Predose at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, and every 12 weeks thereafter to study completion (up to 42 months)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Inclusion Criteria for Arms A, B, and C: Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors Aged 12 years or older at the time of informed consent Body weight ≥40 kilograms (kg) 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 measure during the treatment period and for at least 5 elimination half-lives (24 weeks) after the last dose of study drug Inclusion Criteria for Arm D: Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (i.e., ≥5 BU/mL) Children <12 years old at time of informed consent Body weight >3 kg at time of informed consent Requires treatment with bypassing agents Adequate hematologic, hepatic, and renal function For female participants who are of childbearing potential, follow the same contraception criteria as listed above for Arms A, B, and C Exclusion Criteria: Exclusion Criteria for Arms A, B, and C: Inherited or acquired bleeding disorder other than hemophilia A 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 4 (CD4) count <200 cells/microliter (cells/mcL) within 24 weeks prior to screening. Participants with HIV infection who have 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 Exclusion Criteria for Arm D: Inherited or acquired bleeding disorder other than hemophilia A Ongoing (or plan to receive during the study) ITI therapy or prophylaxis treatment with FVIII 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 diseases 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 infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) At high risk for thrombotic microangiopathy, in the investigator's judgment Use of systemic immunomodulators at enrollment or planned use during the study Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition) 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 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 Pregnant or lactating, or intending to become pregnant during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing City
ZIP/Postal Code
100032
Country
China
Facility Name
Beijing Children's Hospital, Capital Medical University; rheumatism
City
Beijing City
ZIP/Postal Code
100045
Country
China
Facility Name
Xiangya Hospital of Centre-South University
City
Changsha
ZIP/Postal Code
410008
Country
China
Facility Name
Southern Medical University Nanfang Hospital
City
Guangdong Province Guangzhou City
ZIP/Postal Code
510515
Country
China
Facility Name
Ruijin Hospital Shanghai Jiaotong University School of Medicine; hemotology
City
Shanghai City
ZIP/Postal Code
200025
Country
China
Facility Name
Tianjin Institute of Hematology & Blood Diseases Hospital
City
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
City
Wuhan
ZIP/Postal Code
430022
Country
China
Facility Name
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
City
Wuhan
ZIP/Postal Code
430030
Country
China
Facility Name
Queen Mary Hospital; Department of Pediatrics & Adolescent Medicine
City
Hong kong
Country
Hong Kong
Facility Name
Prince of Wales Hospital; Department of Pediatrics
City
Shatin
Country
Hong Kong
Facility Name
Penang General Hospital; Department of Medicine
City
Pulau Pinang
State/Province
Penang
ZIP/Postal Code
10450
Country
Malaysia
Facility Name
Queen Elizabeth Hospital
City
Shah Alam
State/Province
Selangor
ZIP/Postal Code
40170
Country
Malaysia
Facility Name
Ramathibodi Hospital
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand

12. IPD Sharing Statement

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

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