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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02795767




Registration number
NCT02795767
Ethics application status
Date submitted
7/06/2016
Date registered
10/06/2016
Date last updated
2/06/2021

Titles & IDs
Public title
A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors
Scientific title
A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors
Secondary ID [1] 0 0
2016-000073-21
Secondary ID [2] 0 0
BH29992
Universal Trial Number (UTN)
Trial acronym
HAVEN 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Emicizumab

Experimental: Cohort A: 1.5 mg/kg Emicizumab QW - Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Experimental: Cohort B: 3 mg/kg Emicizumab Q2W - Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Experimental: Cohort C: 6 mg/kg Emicizumab Q4W - Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.


Treatment: Drugs: Emicizumab
Emicizumab will be administered as per the schedule specified in the respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [1] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [2] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [2] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [3] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [3] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [4] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [4] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [5] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [5] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [6] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [6] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [7] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [7] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [8] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [8] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [9] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [9] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [10] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [10] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [11] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [11] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [12] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [12] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [13] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [13] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [14] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [14] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [15] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [15] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [16] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [16] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [17] 0 0
Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [17] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [18] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [18] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [19] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [19] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [20] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [20] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Secondary outcome [1] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [1] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [2] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [2] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [3] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [3] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [4] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [4] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [5] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [5] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [6] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [6] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [7] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [7] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [8] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [8] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [9] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [9] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [10] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [10] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [11] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Timepoint [11] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [12] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Timepoint [12] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [13] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Timepoint [13] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [14] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [14] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [15] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [15] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [16] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [16] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [17] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [17] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [18] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [18] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [19] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [19] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [20] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Timepoint [20] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [21] 0 0
Cohort A: Intra-Participant Comparison of the Model-Based ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the Non-Interventional Study (NIS) Population
Timepoint [21] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [22] 0 0
Cohort A: Intra-Participant Comparison of the Model-Based ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Timepoint [22] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [23] 0 0
Cohort A: Intra-Participant Comparison of the Median Calculated ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Timepoint [23] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [24] 0 0
Cohort A: Intra-Participant Comparison of the Median Calculated ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Timepoint [24] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [25] 0 0
Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Timepoint [25] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [26] 0 0
Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Timepoint [26] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [27] 0 0
Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Timepoint [27] 0 0
From Baseline to 52 weeks
Secondary outcome [28] 0 0
Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Timepoint [28] 0 0
From Baseline to 52 weeks
Secondary outcome [29] 0 0
Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Timepoint [29] 0 0
From Baseline to 52 weeks
Secondary outcome [30] 0 0
Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Timepoint [30] 0 0
From Baseline to 52 weeks
Secondary outcome [31] 0 0
Number of Treated Bleeds Over Time in Participants With Dose Up-Titration
Timepoint [31] 0 0
From Baseline to study completion (up to at least 52 weeks)
Secondary outcome [32] 0 0
Number of All Bleeds Over Time in Participants With Dose Up-Titration
Timepoint [32] 0 0
From Baseline to study completion (up to at least 52 weeks)
Secondary outcome [33] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [33] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [34] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [34] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [35] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Timepoint [35] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [36] 0 0
Change From Baseline Over Time in the Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score, as Completed by Treated Participants =8 to <12 Years of Age
Timepoint [36] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [37] 0 0
Change From Baseline Over Time in the Haemo-QoL-SF Questionnaire Physical Health Domain Score, as Completed by Treated Participants =8 to <12 Years of Age
Timepoint [37] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [38] 0 0
Change From Baseline Over Time in Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors Including Aspects of Caregiver Burden (Adapted Inhib-QoL) Questionnaire Total Score, Treated Participants <12 Years of Age
Timepoint [38] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [39] 0 0
Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age
Timepoint [39] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [40] 0 0
Number of Participants With at Least One Adverse Event
Timepoint [40] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [41] 0 0
Number of Participants With at Least One Grade =3 Adverse Event
Timepoint [41] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [42] 0 0
Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment
Timepoint [42] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [43] 0 0
Number of Participants With at Least One Adverse Event of Local Injection Site Reaction
Timepoint [43] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [44] 0 0
Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction
Timepoint [44] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [45] 0 0
Number of Participants With at Least One Adverse Event of Thromboembolic Event
Timepoint [45] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [46] 0 0
Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy
Timepoint [46] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [47] 0 0
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study
Timepoint [47] 0 0
Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)
Secondary outcome [48] 0 0
Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Timepoint [48] 0 0
From Baseline until study completion (up to 188 weeks)
Secondary outcome [49] 0 0
Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Timepoint [49] 0 0
From Baseline until study completion (up to 188 weeks)
Secondary outcome [50] 0 0
Plasma Trough Concentration (Ctrough) of Emicizumab
Timepoint [50] 0 0
Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177

Eligibility
Key inclusion criteria
* Children less than (<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh <40 kilograms (kg) (Cohort A only); and participants <2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)
* Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is [i.e.], greater than or equal to [>/=] 5 bethesda units [BU])
* Requires treatment with bypassing agents
* Adequate hematologic, hepatic, and renal function
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inherited or acquired bleeding disorder other than hemophilia A
* Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII
* Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
* Other disease that may increase risk of bleeding or thrombosis
* History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection
* Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus
* Use of systemic immunomodulators at enrollment or planned use during the study period
* 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)
* Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/11/2020
Sample size
Target
Accrual to date
Final
88
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Costa Rica
State/province [9] 0 0
San Jose
Country [10] 0 0
France
State/province [10] 0 0
Bron
Country [11] 0 0
France
State/province [11] 0 0
Le Kremlin Bicetre
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Bonn
Country [14] 0 0
Italy
State/province [14] 0 0
Lombardia
Country [15] 0 0
Japan
State/province [15] 0 0
Aichi
Country [16] 0 0
Japan
State/province [16] 0 0
Kitakyushu-shi
Country [17] 0 0
Japan
State/province [17] 0 0
Nara
Country [18] 0 0
Japan
State/province [18] 0 0
Shizuoka
Country [19] 0 0
Japan
State/province [19] 0 0
Tokyo
Country [20] 0 0
South Africa
State/province [20] 0 0
Johannesburg
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Sevilla
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
Turkey
State/province [24] 0 0
Adana
Country [25] 0 0
Turkey
State/province [25] 0 0
Istanbul
Country [26] 0 0
Turkey
State/province [26] 0 0
Izmir
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This non-randomized, multicenter, open-label, Phase III clinical study will evaluate the efficacy, safety, and pharmacokinetics of emicizumab administered subcutaneously initially once weekly (QW) in pediatric participants with hemophilia A with FVIII inhibitors. This study will open two additional non-randomized cohorts to investigate once every 2 weeks (Q2W) and once every 4 weeks (Q4W) regimens in pediatric participants.
Trial website
https://clinicaltrials.gov/study/NCT02795767
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02795767