Phase 3
N=152
A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT02847637 ↗Enrolled (actual)
152
Serious AEs
21.3%
Results posted
Nov 2018
Primary outcome: Primary: Annualized Bleeding Rate (ABR) for Treated Bleeds — 38.2; 1.5; 1.3; 1.6 treated bleed rate per year — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Emicizumab (Drug); Factor VIII (FVIII) (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Bleeding Rate (ABR) for Treated Bleeds |
38.2; 1.5; 1.3; 1.6 | <0.0001 sig |
| SECONDARY Annualized Bleeding Rate (ABR) for All Bleeds |
47.6; 2.5; 2.6; 3.3 | <0.0001 sig |
| SECONDARY Annualized Bleeding Rate (ABR) for Treated Joint Bleeds |
26.5; 1.1; 0.9; 1.2 | <0.0001 sig |
| SECONDARY Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds |
15.6; 1.0; 0.3; 0.5 | <0.0001 sig |
| SECONDARY Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds |
13.0; 0.6; 0.7; 0.6 | <0.0001 sig |
| SECONDARY Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With Factor VIII (FVIII) Prophylaxis (NISP) |
4.8; 1.5 | <0.0001 sig |
| SECONDARY Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With FVIII Prophylaxis (NISP) |
8.9; 3.3 | 0.0002 sig |
| SECONDARY Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) |
34.4; 1.0 | <0.0001 sig |
| SECONDARY Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE) |
39.6; 1.6 | <0.0001 sig |
| SECONDARY Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Subscore for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 |
44.32; 31.81; 28.35 | 0.0891 |
| SECONDARY Haem-A-QoL Questionnaire Total Score for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25 |
29.95; 24.04; 21.39 | 0.1269 |
| SECONDARY European Quality of Life 5-Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score in the Randomized Population at Week 25 |
72.57; 76.61; 81.72 | 0.3402 |
| SECONDARY EQ-5D-5L Questionnaire Index Utility Score in the Randomized Population at Week 25 |
0.63; 0.76; 0.76 | 0.0060 sig |
| SECONDARY Hemophilia-Specific Quality of Life - Short Form (Haemo-QoL-SF) Questionnaire Score in Adolescent Participants (12 to 17 Years of Age) in the Randomized Population at Week 25 |
— | — |
| SECONDARY Percentage of Participants With at Least One Adverse Event During the First 24 Weeks of the Study, Primary Analysis |
33.3; 94.4; 85.7; 50.0; 87.3 | — |
| SECONDARY Percentage of Participants With at Least One Grade ≥3 Adverse Event During the First 24 Weeks of the Study, Primary Analysis |
5.6; 8.3; 11.4; 0; 9.3 | — |
| SECONDARY Percentage of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 2.9; 0; 0 | — |
| SECONDARY Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With at Least One Adverse Event of Abnormal Laboratory Values During the First 24 Weeks of the Study, Primary Analysis |
0; 5.6; 17.1; 6.3; 4.8 | — |
| SECONDARY Percentage of Participants With at Least One Local Injection-Site Reaction During the First 24 Weeks of the Study, Primary Analysis |
0; 25.0; 20.0; 12.5; 33.3 | — |
| SECONDARY Percentage of Participants With at Least One Thromboembolic Event During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With at Least One Thrombotic Microangiopathy During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction During the First 24 Weeks of the Study, Primary Analysis |
0; 0; 0; 0; 0 | — |
| SECONDARY Safety Summary of the Percentage of Emicizumab-Treated Participants With at Least One Adverse Event During the Study |
100.0; 97.1; 88.2; 100.0; 98.0; 0.0 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants |
0.8; 0.7; 1.2; 1.5; 1.2; 1.1 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants |
1.2; 0.8; 1.2; 1.7; 1.3; 1.4 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants |
0.4; 0.4; 0.0; 0.5; 0.4; 0.5 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
1.9; 1.9; 1.0; 0.9; 1.0; 1.1 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
3.8; 2.8; 1.8; 1.4; 1.5; 1.6 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
0.7; 0.7; 0.3; 0.4; 0.5; 0.3 | — |
| SECONDARY Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Anti-Emicizumab Antibodies at Any Time Post-Baseline During the Study |
8.3; 5.7; 0.0; 1.6; 4.0; 0.0 | — |
| SECONDARY Percentage of Participants With De Novo Development of Factor VIII (FVIII) Inhibitors |
0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Emicizumab |
NA; NA; NA; NA; NA; NA | — |
Summary
This is a randomized, global, multicenter, open-label, Phase 3 clinical study in participants with severe hemophilia A without inhibitors against Factor VIII (FVIII) who are 12 years or older. The study evaluates two prophylactic emicizumab regimens versus no prophylaxis in this population with emphasis on efficacy, safety, and pharmacokinetics.
Eligibility Criteria
Inclusion Criteria
- Body weight >/= 40 kilogram (kg) at the time of screening
- Diagnosis of severe congenital hemophilia A
- Documentation of the details of prophylactic or episodic FVIII treatment and of number of bleeding episodes for at least the last 24 weeks
- Adequate hematologic function
- Adequate hepatic function
- Adequate renal function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than ( ) 200 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
- 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
- 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) 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
Data sourced from ClinicalTrials.gov (NCT02847637). 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.