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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)

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.
ClinicalTrials.gov Identifier: NCT03020160
Recruitment Status : Active, not recruiting
First Posted : January 13, 2017
Results First Posted : December 25, 2018
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
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
Actual Study Start Date : January 30, 2017
Actual Primary Completion Date : December 15, 2017
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Expansion Part: Annualized Bleeding Rate (ABR) for Treated Bleeds [ Time Frame: From Baseline to at least 24 weeks ]
    The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

  2. Expansion Part: Annualized Bleeding Rate (ABR) for All Bleeds [ Time Frame: From Baseline to at least 24 weeks ]
    The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.

  3. Expansion Part: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds [ Time Frame: From Baseline to at least 24 weeks ]
    The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

  4. Expansion Part: Annualized Bleeding Rate (ABR) for Treated Joint Bleeds [ Time Frame: From Baseline to at least 24 weeks ]
    The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of joint bleeds, excluding bleeds due to surgery/procedure.

  5. Expansion Part: Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds [ Time Frame: From Baseline to at least 24 weeks ]
    The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.


Secondary Outcome Measures :
  1. Expansion Part: Change From Baseline to Week 25 in the Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score for Adult Participants (≥18 Years of Age) [ Time Frame: Baseline, Week 25 ]
    The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.

  2. Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Total Score [ Time Frame: Baseline, Week 25 ]
    The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.

  3. Expansion Part: Change From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score for Adult Participants (≥18 Years of Age) [ Time Frame: Baseline, Week 25 ]
    The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.

  4. Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score [ Time Frame: Baseline, Week 25 ]
    The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.

  5. Expansion Part: Change From Baseline to Week 25 in the Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Total Score for Adolescent Participants (12-17 Years of Age) [ Time Frame: Baseline, Week 25 ]
    The Haemo-QoL-SF was developed in a series of age-related questionnaires to measure health-related quality of life (HRQoL) in children and adolescents with hemophilia. The short version for older children containing 35 items was selected for adolescents in this study. Items are rated along five response options: never, rarely, sometimes, often, or all the time. This version covers nine dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia, and treatment). Scale scores range from 0 to 100, with lower scores indicating better HRQoL. Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.

  6. Expansion Part: Change From Baseline to Week 25 in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score [ Time Frame: Baseline, Week 25 ]
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.

  7. Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire VAS Score [ Time Frame: Baseline, Week 25 ]
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.

  8. Expansion Part: Change From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score [ Time Frame: Baseline, Week 25 ]
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.

  9. Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score [ Time Frame: Baseline, Week 25 ]
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.

  10. Expansion Part: Proportion of Days Away From Work to Expected Days at Work in the Previous Four Weeks [ Time Frame: Predose at Baseline, Weeks 13 and 25, and every 12 weeks thereafter up to study completion/early termination (up to approximately 4 years) ]
    Participants enrolled in the expansion part of the study reported at each time point the number of days away from work (i.e., days of work missed) and the expected number of days at work in the previous four weeks, which is reported here for each time point as the proportion of the number of days away from work to the expected number of days at work.

  11. Expansion Part: Proportion of Days Away From School to Expected Days at School in the Previous Four Weeks [ Time Frame: Predose at Baseline, Weeks 13 and 25, and every 12 weeks thereafter up to study completion/early termination (up to approximately 4 years) ]
    Participants enrolled in the expansion part of the study reported at each time point the number of days away from school (i.e., days of school missed) and the expected number of days at school in the previous four weeks, which is reported here as the proportion of the number of days away from school to the expected number of days at school.

  12. Expansion Part: Number of Days Hospitalized [ Time Frame: From Baseline until at least 24 weeks of treatment through to study completion (up to approximately 4 years) ]
    At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks); all participants had completed at least 24 weeks of treatment.

  13. Expansion Part: Percentage of Participants Who Preferred Either the New Emicizumab Subcutaneous (SC) Treatment or Their Previous Hemophilia Intravenous (IV) Treatment, or Had No Preference, as Assessed Using the Emicizumab Preference Survey [ Time Frame: Predose at Week 17 ]
    The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with intravenous (IV) factor VIIII (FVIII) or subcutaneous (SC) emicizumab, or no preference.

  14. PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab [ Time Frame: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
  15. PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab [ Time Frame: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
  16. 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: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
  17. 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: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
  18. PK Run-In Part: Apparent Plasma Terminal Half-Life (t1/2) of Emicizumab [ Time Frame: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
  19. PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab [ Time Frame: Predose (0 hr) and 8 hrs postdose on Day 1; Days 3,5,8,11,15,18,22,25,29,36,43,50,57,85,113,141,148,155,162,169, once between 2 emicizumab administrations between Weeks 9 and 21, and once every 12 weeks from Week 25 to study completion (up to 4 years) ]
    Only CL/F is reported after the first dose; the apparent clearance at steady state (CLss/F) is reported after the sixth dose instead. This is because t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule, and dependent PK parameters, such as CL/F, could not be estimated.

  20. Expansion Part: Minimum Observed Plasma Concentration (Cmin) of Emicizumab [ Time Frame: Predose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, and once every 12 weeks from Week 25 to study completion (up to approximately 4 years) ]
  21. Number of Participants With At Least One Adverse Event [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  22. Number of Participants With Grade ≥3 Adverse Events [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    The World Health Organization (WHO) toxicity grading scale will be used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  23. Number of Participants With Adverse Events Leading to Withdrawal From Treatment [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  24. Number of Participants With Adverse Events of Changes From Baseline in Vital Signs [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  25. Number of Participants With Adverse Events of Changes From Baseline in Physical Examination Findings [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  26. Number of Participants With Adverse Events of Abnormal Laboratory Values [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]

    The number of participants with adverse events of abnormal laboratory values is reported here. An abnormal laboratory value is defined as a laboratory test result outside of the normal range for hematology or serum chemistries.

    It is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).


  27. Number of Participants With Local Injection-Site Reactions [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction." At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  28. Number of Participants With Thromboembolic Events [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  29. Number of Participants With Thrombotic Microangiopathy [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  30. Number of Participants With Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions [ Time Frame: From Baseline to study completion (up to approximately 4 years) ]
    At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  31. Number of Participants With Anti-Drug Antibodies to Emicizumab [ Time Frame: Baseline, Weeks 5, 9, 13, 17, 21, and 25, and every 12 weeks thereafter until study completion (up to approximately 4 years) ]
    A validated ELISA method was used to analyze the levels of anti-drug antibodies to emicizumab in blood plasma samples. A sample was considered positive for anti-drug antibodies if the test result reached or exceeded a pre-determined threshold. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).

  32. Number of Participants With De Novo Development of Anti-Factor VIII (FVIII) Antibodies [ Time Frame: Baseline, Weeks 9 and 17 (for non-inhibitor subjects only), Week 25, and every 12 weeks thereafter until study completion (up to approximately 4 years) ]
    The levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold. At the clinical cut-off date for primary analysis (15 Dec 2017), the median observation time was 43.71 weeks (range: 41.7-45.7 weeks).



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.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
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

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
Layout table for location information
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
Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów 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
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] July 25, 2017
Statistical Analysis Plan  [PDF] June 20, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03020160     History of Changes
Other Study ID Numbers: BO39182
2016-001094-33 ( EudraCT Number )
First Posted: January 13, 2017    Key Record Dates
Results First Posted: December 25, 2018
Last Update Posted: March 6, 2019
Last Verified: March 2019

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

Additional relevant MeSH terms:
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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