Phase 3
N=88
A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT02795767 ↗Enrolled (actual)
88
Serious AEs
30.7%
Results posted
Apr 2019
Primary outcome: Primary: Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age — 0.3 treated bleed rate per year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Emicizumab (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.3 | — |
| PRIMARY Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
3.2 | — |
| PRIMARY Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.2 | — |
| PRIMARY Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
NA | — |
| PRIMARY Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.3 | — |
| PRIMARY Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
3.2 | — |
| PRIMARY Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.2 | — |
| PRIMARY Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
0.1 | — |
| PRIMARY Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
0.6 | — |
| PRIMARY Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
0.0 | — |
| PRIMARY Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
76.9; 100.0; 100.0; 0.0 | — |
| PRIMARY Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
49.2; 72.3; 92.3; 7.7 | — |
| PRIMARY Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
96.9; 100.0; 100.0; 0.0 | — |
| PRIMARY Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
84.6; 100.0; 100.0; 0.0 | — |
| PRIMARY Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
95.4; 100.0; 100.0; 0.0 | — |
| SECONDARY Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.2; 2.2 | — |
| SECONDARY Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
1.5; 3.8 | — |
| SECONDARY Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
NA; 0.8 | — |
| SECONDARY Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.2; 1.7 | — |
| SECONDARY Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
0.2; 0.5 | — |
| SECONDARY Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.2; 2.5 | — |
| SECONDARY Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
1.5; 4.0 | — |
| SECONDARY Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
0.0; 0.8 | — |
| SECONDARY Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.2; 1.9 | — |
| SECONDARY Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
0.2; 0.5 | — |
| SECONDARY Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age |
0.0; 0.0 | — |
| SECONDARY Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age |
0.0; 1.6 | — |
| SECONDARY Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age |
0.0; 0.0 | — |
| SECONDARY Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age |
0.0; 0.0 | — |
| SECONDARY Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age |
0.0; 0.0 | — |
| SECONDARY Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
90.0; 60.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age |
60.0; 50.0; 100.0; 90.0; 100.0; 100.0 | — |
| SECONDARY 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 |
100.0; 90.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY 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 |
90.0; 60.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY 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 |
90.0; 90.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY 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 |
19.9; 0.2 | — |
| SECONDARY 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 |
31.9; 3.3 | — |
| SECONDARY 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 |
16.2; 0.0 | — |
| SECONDARY 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 |
21.3; 1.1 | — |
| SECONDARY 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 |
5.6; 72.2; 16.7; 100.0; 66.7; 100.0 | — |
| SECONDARY 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 |
0.0; 33.3; 11.1; 72.2; 44.4; 83.3 | — |
| SECONDARY Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight |
0.8 | — |
| SECONDARY Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight |
1.4 | — |
| SECONDARY Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight |
0.9 | — |
| SECONDARY Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight |
0.9 | — |
| SECONDARY Number of Treated Bleeds Over Time in Participants With Dose Up-Titration |
— | — |
| SECONDARY Number of All Bleeds Over Time in Participants With Dose Up-Titration |
— | — |
| SECONDARY 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 |
0.3; 0.2; 1.8; 3.0; 0.8; 2.4 | — |
| SECONDARY 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 |
0.3; 0.2; 2.2; 3.0; 0.8; 3.0 | — |
| SECONDARY 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 |
0.0; 0.0; 0.0; 0.7; 0.8; 0.6 | — |
| SECONDARY 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 |
33.37; 25.60; 25.12; -7.02; -9.17; 0.29 | — |
| SECONDARY 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 |
29.51; 30.21; 19.79; -18.40; -23.96; 3.75 | — |
| SECONDARY 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 |
43.10; 40.56; 31.45; -19.76; -21.46; -9.24 | — |
| SECONDARY Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age |
37.13; 34.64; 20.00; -31.10; -30.00; -6.35 | — |
| SECONDARY Number of Participants With at Least One Adverse Event |
64; 9; 10 | — |
| SECONDARY Number of Participants With at Least One Grade ≥3 Adverse Event |
15; 1; 3 | — |
| SECONDARY Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment |
0; 0; 1 | — |
| SECONDARY Number of Participants With at Least One Adverse Event of Local Injection Site Reaction |
23; 2; 6 | — |
| SECONDARY Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction |
1; 0; 0 | — |
| SECONDARY Number of Participants With at Least One Adverse Event of Thromboembolic Event |
0; 0; 0 | — |
| SECONDARY Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy |
0; 0; 0 | — |
| SECONDARY Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study |
63; 10; 9; 59; 10; 9 | — |
| SECONDARY Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline |
53; 10; 9; 3; 0; 1 | — |
| SECONDARY Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline |
49; 8; 6; 4; 1; 0 | — |
| SECONDARY Plasma Trough Concentration (Ctrough) of Emicizumab |
NA; NA; NA; 18.2; 17.0; 17.2 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Children less than ( /=] 5 bethesda units [BU])
- Requires treatment with bypassing agents
- Adequate hematologic, hepatic, and renal function
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
Data sourced from ClinicalTrials.gov (NCT02795767). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.