Hemophilia A
Conditions
Brief summary
This multicenter, open-label study will evaluate the safety, efficacy and pharmacokinetics of prophylactic emicizumab treatment in participants previously treated with episodic or prophylactic bypassing agents. Episodic bypassing agent participants will be randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) versus no prophylaxis (Arm B) and will be stratified across Arms A and B according to the number of bleeds they experienced over the last 24 weeks prior to study entry (less than \[\<\] 9 or greater than or equal to \[\>/=\] 9 bleeds); Arm B participants will have the opportunity to switch to emicizumab prophylaxis after at least 24 weeks on-study. Prophylactic bypassing agent participants will switch to emicizumab prophylaxis (Arm C) from the start of the trial; enrollment will be extended for 24 weeks after the last participant has enrolled in Arms A or B or until approximately 50 participants have enrolled in Arm C, whichever occurs first. Episodic bypassing agent participants who previously participated in the non-interventional study BH29768 (NCT02476942) who were unable to enroll in Arms A or B, or participants on prophylactic bypassing agents who were unable to enroll in Arm C, prior to their closure will have the opportunity to enroll in Arm D. Like participants in Arms A and C, Arm D participants will receive emicizumab prophylaxis from the start of the trial. All participants will continue to receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with recombinant activated factor VII (rFVIIa).
Interventions
DRUGEmicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
DRUGrFVIIa
Participants will continue to receive rFVIIa.
DRUGaPCC
Participants will continue to receive aPCC.
Sponsors
Chugai Pharmaceutical
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight \>/= 40 kilograms (kg) at the time of screening * Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor ( that is \[i.e.\], \>/= 5 Bethesda Units \[BU\]) * Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks * \>/= 6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing agent regimen) or \>/=2 bleeds in the last 24 weeks prior to screening (if on a prophylactic bypassing agent regimen) * Adequate hematologic, hepatic and renal function * For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective contraceptive methods
Exclusion criteria
* Participants with inherited or acquired bleeding disorder other than hemophilia A * Participants with ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of participants who have received a treatment regimen of FVIII prophylaxis with concurrent bypassing agent prophylaxis * Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease * Participants with other conditions (for example \[e.g.\], certain autoimmune diseases) that may increase the risk of bleeding or thrombosis * History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection * Known human immunodeficiency virus (HIV) infection with cluster of differentiation 4 (CD4) count \< 200 cells per microliter (cells/mcL) within 24 weeks prior to screening * Use of systemic immunomodulators (e.g., interferon or rituximab) at enrolment or planned use during the study, with the exception of antiretroviral therapy * 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 judgment * Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the participant's safe participation in and completion of the study or interpretation of the study results * 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 within last 30 days or 5 half-lives, whichever is shorter; An investigational drug concurrently * Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority) * Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant * Pregnancy or lactation, or intent to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of treated bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks | This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks | This was an intra-participant comparison of the ABRs for treated bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose. |
| Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of treated joint bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated joint bleeds were defined as treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Bleeds due to surgery/procedure were excluded. |
| Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks | This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm C participants who had previously received prophylactic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks | This was an intra-participant comparison of the ABRs for treated bleeds in Arm C participants who had previously received bypassing agent prophylaxis during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose. |
| Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of treated spontaneous bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of treated target joint bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated target joint bleeds included treated (with coagulation factors) joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Physical Health Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | Week 25 | Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health). |
| Haem-A-QoL Questionnaire Total Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | Week 25 | Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Questionnaire Total Score is the average of the all domain scores and range from 0 to 100, with lower scores reflective of better quality of life. |
| European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale 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. |
| Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks) | The number of all bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Baseline and Week 25 (for Arm B (Emi), Study Weeks are relative to first emicizumab dose) | The Haemo-QoL-SF contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated with five respective response options: never, seldom, sometimes, often, and always. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life. Baseline was defined as the last assessment prior to treatment. Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose; baseline for Arm B (Emi) is the same as Week 25 for Arm B (Control). |
| Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks) | The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks) | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks) | The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded. |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks | The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose. |
| Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) | Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms severe and serious are not synonymous; severity and seriousness were independently assessed for each AE. For participants whose emicizumab dose was up-titrated, only data before up-titration is included. aPCC = activated prothrombin complex concentrate; Hypersens.= hypersensitivity |
| Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) | 'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs. |
| Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Pre-dose (0 hour [hr]) on Weeks 1-5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, and 169 (For Arm B (Emi), Study Weeks are relative to first emicizumab dose) | Plasma concentrations of emicizumab were analyzed using a validated Enzyme Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) was 100 nanograms per milliliter (ng/mL). Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose. |
| EQ-5D-5L Index Utility Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Week 25 | EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single utility index value ranging from 1 to 5, where 1 indicates better health state (no problems) and 5 indicates worst health state (confined to bed). |
Countries
Australia, Costa Rica, France, Germany, Italy, Japan, New Zealand, Poland, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 113 participants were enrolled in this study: 109 participants prior to the primary completion date plus a further 4 participants to Arm D of the study after the primary completion date. Participants in Arm A and Arm B were randomized in a 2:1 ratio; participants in Arm C and Arm D were enrolled without randomization.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds. | 35 |
| Arm B (Control): No Prophylaxis, Then Emicizumab Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds. | 18 |
| Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds. | 49 |
| Arm D: 1.5 mg/kg Emicizumab QW Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds. | 11 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm A: 1.5 mg/kg Emicizumab QW | Arm B (Control): No Prophylaxis, Then Emicizumab | Arm C: 1.5 mg/kg Emicizumab QW | Arm D: 1.5 mg/kg Emicizumab QW | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 13.9 | 37.2 years STANDARD_DEVIATION 13.7 | 25.6 years STANDARD_DEVIATION 16.8 | 39.0 years STANDARD_DEVIATION 16.1 | 31.9 years STANDARD_DEVIATION 16.2 |
| Age, Customized Adolescents (12-17 years) | 4 Participants | 2 Participants | 26 Participants | 0 Participants | 32 Participants |
| Age, Customized Adults (18-64 years) | 30 Participants | 15 Participants | 21 Participants | 10 Participants | 76 Participants |
| Age, Customized Elderly (65-84 years) | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 12 Participants | 1 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 17 Participants | 37 Participants | 10 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants by the Number of Bleeds (<9 or ≥9) in the Last 24 Weeks Prior to Study Entry <9 Bleeds | 11 Participants | 5 Participants | 23 Participants | 6 Participants | 45 Participants |
| Number of Participants by the Number of Bleeds (<9 or ≥9) in the Last 24 Weeks Prior to Study Entry ≥9 Bleeds | 24 Participants | 13 Participants | 26 Participants | 5 Participants | 68 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 3 Participants | 8 Participants | 0 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 3 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 21 Participants | 10 Participants | 33 Participants | 11 Participants | 75 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 18 Participants | 49 Participants | 11 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 18 | 0 / 18 | 1 / 49 | 0 / 11 |
| other Total, other adverse events | 33 / 34 | 9 / 18 | 15 / 18 | 42 / 49 | 9 / 11 |
| serious Total, serious adverse events | 11 / 34 | 5 / 18 | 4 / 18 | 9 / 49 | 2 / 11 |
Outcome results
Primary
Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of treated bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: Intent-to-treat (ITT) population defined as all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 2.9 treated bleeds per year |
| Arm B (Control): No Prophylaxis | Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 23.3 treated bleeds per year |
Comparison: Analysis was performed using an NB regression model, which accounted for different follow-up times, with the participant's number of bleeds as a function of randomization and the time that each participant stays in the study included as an offset in the model. The model also included the number of bleeds (less than \[\<\] 9 or greater than or equal to \[\>/=\] 9) in the last 24 weeks prior to study entry as a stratification factor in the randomization.p-value: <0.000195% CI: [0.057, 0.277]Stratified Wald Test
Secondary
EQ-5D-5L Index Utility Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single utility index value ranging from 1 to 5, where 1 indicates better health state (no problems) and 5 indicates worst health state (confined to bed).
Time frame: Week 25
Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of participants in Arms A and B who responded to the questionnaire at Week 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | EQ-5D-5L Index Utility Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 0.83 score on a scale | Standard Deviation 0.22 |
| Arm B (Control): No Prophylaxis | EQ-5D-5L Index Utility Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 0.60 score on a scale | Standard Deviation 0.35 |
Comparison: Actual number of participants included for inferential statistics in Arm A is 29. Means adjusted for covariates: baseline score, treatment group and treatment by baseline interaction arm.p-value: 0.001495% CI: [-0.25, -0.07]ANCOVA
Secondary
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale 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.
Time frame: Week 25
Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of participants in Arms A and B who responded to the questionnaire at Week 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 83.8 score on a scale | Standard Deviation 12.9 |
| Arm B (Control): No Prophylaxis | European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 76.4 score on a scale | Standard Deviation 15.7 |
Comparison: Actual number of participants included for inferential statistics in Arm A is 29. Means adjusted for covariates: baseline score, treatment group and treatment by baseline interaction arm.p-value: 0.017195% CI: [-17.62, -1.82]ANCOVA
Secondary
Haem-A-QoL Questionnaire Total Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis
Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Questionnaire Total Score is the average of the all domain scores and range from 0 to 100, with lower scores reflective of better quality of life.
Time frame: Week 25
Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of adult participants (≥18 years old) in Arms A and B who responded to the questionnaire at Week 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Haem-A-QoL Questionnaire Total Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | 26.465 score on a scale | Standard Deviation 18.666 |
| Arm B (Control): No Prophylaxis | Haem-A-QoL Questionnaire Total Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | 47.504 score on a scale | Standard Deviation 17.435 |
Comparison: Actual number of participants included for inferential statistics in Arm A is 25. Means adjusted for covariates: baseline score, treatment group and treatment by baseline interaction arm.p-value: 0.001995% CI: [5.56, 22.45]ANCOVA
Secondary
Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Physical Health Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis
Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health).
Time frame: Week 25
Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of adult participants (≥18 years old) in Arms A and B who responded to the questionnaire at Week 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Physical Health Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | 30.19 score on a scale | Standard Deviation 26.59 |
| Arm B (Control): No Prophylaxis | Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Physical Health Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis | 57.14 score on a scale | Standard Deviation 23.35 |
Comparison: Actual number of participants included for inferential statistics in Arm A is 25. Means adjusted for covariates: baseline score, treatment group and treatment by baseline interaction arm. Analysis was performed using Analysis of Covariance (ANCOVA).p-value: 0.002995% CI: [7.89, 35.22]ANCOVA
Secondary
Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old)
The Haemo-QoL-SF contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated with five respective response options: never, seldom, sometimes, often, and always. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life. Baseline was defined as the last assessment prior to treatment. Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose; baseline for Arm B (Emi) is the same as Week 25 for Arm B (Control).
Time frame: Baseline and Week 25 (for Arm B (Emi), Study Weeks are relative to first emicizumab dose)
Population: The number analyzed is the number of adolescent participants (12-17 years old) who responded to the questionnaire at baseline and Week 25. Arm D is excluded because no adolescents were enrolled in that arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Baseline | 34.643 units on a scale | Standard Deviation 22.728 |
| Arm A: 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Week 25 | 33.095 units on a scale | Standard Deviation 17.559 |
| Arm B (Control): No Prophylaxis | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Week 25 | 30.000 units on a scale | Standard Deviation 14.142 |
| Arm B (Control): No Prophylaxis | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Baseline | 37.143 units on a scale | Standard Deviation 12.122 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Baseline | 30.000 units on a scale | Standard Deviation 14.142 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Week 25 | 12.143 units on a scale | Standard Deviation 7.071 |
| Arm C: 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Baseline | 30.714 units on a scale | Standard Deviation 15.625 |
| Arm C: 1.5 mg/kg Emicizumab QW | Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) | Week 25 | 19.286 units on a scale | Standard Deviation 14.507 |
Secondary
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents
This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks
Population: Arm A NIS population included all Arm A participants who participated in NIS BH29768 before study entry and received episodic bypassing agents during NIS BH29768.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | 4.1 all bleeds per year |
| Arm B (Control): No Prophylaxis | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | 37.7 all bleeds per year |
Comparison: This intra-participant comparison of ABR for all bleeds was performed using an NB regression model.p-value: <0.000195% CI: [0.055, 0.218]Non-Stratified Wald Test
Secondary
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents
This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm C participants who had previously received prophylactic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks
Population: Arm C NIS population included all Arm C participants who participated in NIS BH29768 before study entry and received prophylactic bypassing agents during NIS BH29768.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | 5.5 all bleeds per year |
| Arm B (Control): No Prophylaxis | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | 24.3 all bleeds per year |
Comparison: This intra-participant comparison of ABR for all bleeds was performed using an NB regression model.p-value: <0.000195% CI: [0.119, 0.435]Non-Stratified Wald Test
Secondary
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents
This was an intra-participant comparison of the ABRs for treated bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose.
Time frame: Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks
Population: Arm A NIS population included all Arm A participants who participated in NIS BH29768 before study entry and received episodic bypassing agents during NIS BH29768.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | 1.7 treated bleeds per year |
| Arm B (Control): No Prophylaxis | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents | 21.6 treated bleeds per year |
Comparison: This intra-participant comparison of ABR for treated bleeds was performed using an NB regression model.p-value: <0.000195% CI: [0.031, 0.198]Non-Stratified Wald Test
Secondary
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents
This was an intra-participant comparison of the ABRs for treated bleeds in Arm C participants who had previously received bypassing agent prophylaxis during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a treatment for bleed. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose.
Time frame: Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks
Population: Arm C NIS population included all Arm C participants who participated in NIS BH29768 before study entry and received prophylactic bypassing agents during NIS BH29768.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | 3.3 treated bleeds per year |
| Arm B (Control): No Prophylaxis | Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents | 15.7 treated bleeds per year |
Comparison: This intra-participant comparison of ABR for treated bleeds was performed using an NB regression model.p-value: 0.000395% CI: [0.089, 0.486]Non-Stratified Wald Test
Secondary
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 6.2 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 3.4 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 1.5 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 1.4 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 1.1 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 1.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 1.3 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 1.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 1.2 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.9 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.8 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.5 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.8 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.3 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.8 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.2 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 all bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.9 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 2.9 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.4 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 4.8 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 1.2 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.2 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 1.3 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.6 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 2.2 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 3.3 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 4.6 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.4 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.3 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.4 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 1.6 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.4 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.9 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 2.5 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 1.5 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.5 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 2.6 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.3 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 3.9 bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 3.9 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 2.2 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 0.9 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 0.3 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 0.4 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 0.5 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 0.6 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 0.4 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 0.5 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.4 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.5 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.4 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.2 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.2 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 treated bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 2.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 1.3 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 0.4 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 0.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 0.1 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 0.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 0.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 0.1 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 0.3 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.1 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.4 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.2 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 treated spontaneous bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 all bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 all bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.3 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 1.9 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 0.5 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.0 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.0 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 0.6 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.0 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.0 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.0 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.0 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.0 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 0.5 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.0 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.0 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.0 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 0.6 bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 treated bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 treated bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants
The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 1 to 12 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 13 to 24 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 25 to 36 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 37 to 48 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 49 to 60 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 61 to 72 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 73 to 84 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 85 to 96 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 97 to 108 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 109 to 120 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 121 to 132 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 133 to 144 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 145 to 156 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 157 to 168 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 169 to 180 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 181 to 192 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 193 to 204 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 205 to 216 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 217 to 228 Weeks | 0.0 treated spontaneous bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants | 229 to 240 Weeks | 0.0 treated spontaneous bleeds per year |
Secondary
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants
The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)
Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.5 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 1.9 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.1 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 3.5 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.6 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 1.3 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.01 bleeds per year |
| Arm B (Control): No Prophylaxis | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 0.6 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 2.1 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 3.2 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 4.3 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.4 bleeds per year |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.3 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.3 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 1.5 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.4 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 0.8 bleeds per year |
| Arm C: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 2.3 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Spontaneous Bleeds | 1.3 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Joint Bleeds | 0.4 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Bleeds | 2.4 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | Treated Target Joint Bleeds | 0.2 bleeds per year |
| All Participants: 1.5 mg/kg Emicizumab QW | Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants | All Bleeds | 3.6 bleeds per year |
Secondary
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 3.5 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 6.3 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 1.5 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 1.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 0.4 bleeds per year |
| Arm B (Control): No Prophylaxis | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 18.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 26.2 bleeds per year |
| Arm B (Control): No Prophylaxis | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 8.1 bleeds per year |
| Arm B (Control): No Prophylaxis | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 30.8 bleeds per year |
| Arm B (Control): No Prophylaxis | Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 6.2 bleeds per year |
Secondary
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 0.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 0.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 2.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 0.0 bleeds per year |
| Arm A: 1.5 mg/kg Emicizumab QW | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 0.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 1.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 15.2 bleeds per year |
| Arm B (Control): No Prophylaxis | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 18.8 bleeds per year |
| Arm B (Control): No Prophylaxis | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 1.0 bleeds per year |
| Arm B (Control): No Prophylaxis | Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 30.2 bleeds per year |
Secondary
Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of all bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 5.5 all bleeds per year |
| Arm B (Control): No Prophylaxis | Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 28.3 all bleeds per year |
Comparison: Analysis was performed using an NB regression model, which accounted for different follow-up times, with the participant's number of bleeds as a function of randomization and the time that each participant stays in the study included as an offset in the model. The model also included the number of bleeds (\<9 or \>/=9) in the last 24 weeks prior to study entry as a stratification factor in the randomization.p-value: <0.000195% CI: [0.102, 0.375]Stratified Wald Test
Secondary
Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of treated joint bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated joint bleeds were defined as treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Bleeds due to surgery/procedure were excluded.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 0.8 treated joint bleeds per year |
| Arm B (Control): No Prophylaxis | Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 6.7 treated joint bleeds per year |
Comparison: Analysis was performed using an NB regression model, which accounted for different follow-up times, with the participant's number of bleeds as a function of randomization and the time that each participant stays in the study included as an offset in the model. The model also included the number of bleeds (\<9 or \>/=9) in the last 24 weeks prior to study entry as a stratification factor in the randomization.p-value: 0.00595% CI: [0.025, 0.52]Stratified Wald Test
Secondary
Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of treated spontaneous bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 1.3 treated spontaneous bleeds per year |
| Arm B (Control): No Prophylaxis | Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 16.8 treated spontaneous bleeds per year |
Comparison: Analysis was performed using an NB regression model, which accounted for different follow-up times, with the participant's number of bleeds as a function of randomization and the time that each participant stays in the study included as an offset in the model. The model also included the number of bleeds (\<9 or \>/=9) in the last 24 weeks prior to study entry as a stratification factor in the randomization.p-value: <0.000195% CI: [0.037, 0.154]Stratified Wald Test
Secondary
Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
The number of treated target joint bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated target joint bleeds included treated (with coagulation factors) joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 0.1 treated target joint bleeds per year |
| Arm B (Control): No Prophylaxis | Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | 3.0 treated target joint bleeds per year |
Comparison: Analysis was performed using an NB regression model, which accounted for different follow-up times, with the participant's number of bleeds as a function of randomization and the time that each participant stays in the study included as an offset in the model. The model also included the number of bleeds (\<9 or \>/=9) in the last 24 weeks prior to study entry as a stratification factor in the randomization.p-value: 0.000295% CI: [0.009, 0.227]Stratified Wald Test
Secondary
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study
'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.
Time frame: From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks)
Population: All emicizumab-treated participants included Arms A, C, and D and Arm B participants who switched to receive emicizumab (Arm B Emi). The overall number of participants analyzed is the number of participants with at least one post-baseline anti-drug antibody assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative (Treatment Unaffected) | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Positive (Boosted + Induced) | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive with Neutralizing ADAs | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Induced) | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Boosted) | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative | 33 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Negative (Neg+Neg Unaffected) | 33 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Boosted) | 0 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Positive (Boosted + Induced) | 0 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative | 17 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Induced) | 0 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Negative (Neg+Neg Unaffected) | 18 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive with Neutralizing ADAs | 0 Participants |
| Arm B (Control): No Prophylaxis | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative (Treatment Unaffected) | 1 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Positive (Boosted + Induced) | 2 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Boosted) | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Induced) | 2 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive with Neutralizing ADAs | 2 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Negative (Neg+Neg Unaffected) | 47 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative | 46 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative (Treatment Unaffected) | 1 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Negative (Neg+Neg Unaffected) | 11 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive with Neutralizing ADAs | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | Total ADA Positive (Boosted + Induced) | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative (Treatment Unaffected) | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Induced) | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Positive, Positive (Treatment Boosted) | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study | ADA Negative, Negative | 11 Participants |
Secondary
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis
Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (\>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.
Time frame: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
Population: ITT population: all participants who were randomized to Arm A or Arm B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 62.9 Percentage of participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 68.6 Percentage of participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 94.3 Percentage of participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 85.7 Percentage of participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 37.1 Percentage of participants |
| Arm B (Control): No Prophylaxis | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Target Joint Bleeds | 50.0 Percentage of participants |
| Arm B (Control): No Prophylaxis | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Bleeds | 5.6 Percentage of participants |
| Arm B (Control): No Prophylaxis | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | All Bleeds | 5.6 Percentage of participants |
| Arm B (Control): No Prophylaxis | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Spontaneous Bleeds | 11.1 Percentage of participants |
| Arm B (Control): No Prophylaxis | Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis | Treated Joint Bleeds | 50.0 Percentage of participants |
Secondary
Plasma Trough Concentrations of Emicizumab at Specified Timepoints
Plasma concentrations of emicizumab were analyzed using a validated Enzyme Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) was 100 nanograms per milliliter (ng/mL). Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose.
Time frame: Pre-dose (0 hour [hr]) on Weeks 1-5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, and 169 (For Arm B (Emi), Study Weeks are relative to first emicizumab dose)
Population: Pharmacokinetic (PK) evaluable population included all participants who received at least one dose of emicizumab and had at least one post-dose emicizumab concentration result. The number analyzed includes participants with PK samples at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 169 | 55.0 micrograms per milliliter (mcg/mL) | Standard Deviation 19.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 7 | 52.8 micrograms per milliliter (mcg/mL) | Standard Deviation 16.2 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 4 | 43.8 micrograms per milliliter (mcg/mL) | Standard Deviation 12.2 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 21 | 52.6 micrograms per milliliter (mcg/mL) | Standard Deviation 17.4 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 1 | NA micrograms per milliliter (mcg/mL) | — |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 109 | 49.6 micrograms per milliliter (mcg/mL) | Standard Deviation 15.9 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 9 | 50.4 micrograms per milliliter (mcg/mL) | Standard Deviation 12.4 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 85 | 56.9 micrograms per milliliter (mcg/mL) | Standard Deviation 18.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 17 | 50.7 micrograms per milliliter (mcg/mL) | Standard Deviation 15 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 49 | 48.0 micrograms per milliliter (mcg/mL) | Standard Deviation 12.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 145 | 51.3 micrograms per milliliter (mcg/mL) | Standard Deviation 16.6 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 13 | 49.3 micrograms per milliliter (mcg/mL) | Standard Deviation 13.4 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 41 | 45.3 micrograms per milliliter (mcg/mL) | Standard Deviation 13.7 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 73 | 55.5 micrograms per milliliter (mcg/mL) | Standard Deviation 14.9 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 33 | 50.7 micrograms per milliliter (mcg/mL) | Standard Deviation 17.2 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 97 | 53.2 micrograms per milliliter (mcg/mL) | Standard Deviation 15.2 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 121 | 53.8 micrograms per milliliter (mcg/mL) | Standard Deviation 16.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 3 | 31.6 micrograms per milliliter (mcg/mL) | Standard Deviation 7.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 25 | 54.6 micrograms per milliliter (mcg/mL) | Standard Deviation 19.1 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 157 | 58.0 micrograms per milliliter (mcg/mL) | Standard Deviation 16.5 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 5 | 53.5 micrograms per milliliter (mcg/mL) | Standard Deviation 15.1 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 61 | 52.2 micrograms per milliliter (mcg/mL) | Standard Deviation 16.3 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 133 | 50.5 micrograms per milliliter (mcg/mL) | Standard Deviation 15.9 |
| Arm A: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 2 | 16.2 micrograms per milliliter (mcg/mL) | Standard Deviation 4.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 41 | 49.3 micrograms per milliliter (mcg/mL) | Standard Deviation 25.9 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 61 | 51.8 micrograms per milliliter (mcg/mL) | Standard Deviation 33.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 109 | 32.8 micrograms per milliliter (mcg/mL) | Standard Deviation 31.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 73 | 45.6 micrograms per milliliter (mcg/mL) | Standard Deviation 26.2 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 85 | 42.5 micrograms per milliliter (mcg/mL) | Standard Deviation 34.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 4 | 44.6 micrograms per milliliter (mcg/mL) | Standard Deviation 18.6 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 97 | 34.4 micrograms per milliliter (mcg/mL) | Standard Deviation 26.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 5 | 52.2 micrograms per milliliter (mcg/mL) | Standard Deviation 14.2 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 7 | 53.3 micrograms per milliliter (mcg/mL) | Standard Deviation 18 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 145 | 38.2 micrograms per milliliter (mcg/mL) | Standard Deviation 19 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 9 | 48.9 micrograms per milliliter (mcg/mL) | Standard Deviation 16.7 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 2 | 21.7 micrograms per milliliter (mcg/mL) | Standard Deviation 10.6 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 13 | 45.2 micrograms per milliliter (mcg/mL) | Standard Deviation 16.2 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 17 | 46.5 micrograms per milliliter (mcg/mL) | Standard Deviation 17.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 133 | 48.7 micrograms per milliliter (mcg/mL) | Standard Deviation 29.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 21 | 44.5 micrograms per milliliter (mcg/mL) | Standard Deviation 15.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 25 | 45.8 micrograms per milliliter (mcg/mL) | Standard Deviation 18.6 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 33 | 48.1 micrograms per milliliter (mcg/mL) | Standard Deviation 21.1 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 3 | 32.3 micrograms per milliliter (mcg/mL) | Standard Deviation 10.4 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 121 | 36.1 micrograms per milliliter (mcg/mL) | Standard Deviation 33.6 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 49 | 54.6 micrograms per milliliter (mcg/mL) | Standard Deviation 27.6 |
| Arm B (Control): No Prophylaxis | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 1 | NA micrograms per milliliter (mcg/mL) | — |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 3 | 31.7 micrograms per milliliter (mcg/mL) | Standard Deviation 8.3 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 21 | 51.6 micrograms per milliliter (mcg/mL) | Standard Deviation 17.1 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 145 | 44.0 micrograms per milliliter (mcg/mL) | Standard Deviation 21.7 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 5 | 54.0 micrograms per milliliter (mcg/mL) | Standard Deviation 13.2 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 169 | 43.2 micrograms per milliliter (mcg/mL) | Standard Deviation 20.2 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 157 | 45.5 micrograms per milliliter (mcg/mL) | Standard Deviation 17 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 25 | 50.4 micrograms per milliliter (mcg/mL) | Standard Deviation 16.8 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 4 | 44.7 micrograms per milliliter (mcg/mL) | Standard Deviation 11.5 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 121 | 46.3 micrograms per milliliter (mcg/mL) | Standard Deviation 12.5 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 97 | 54.6 micrograms per milliliter (mcg/mL) | Standard Deviation 20 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 61 | 60.9 micrograms per milliliter (mcg/mL) | Standard Deviation 27.7 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 33 | 54.8 micrograms per milliliter (mcg/mL) | Standard Deviation 16.7 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 109 | 47.4 micrograms per milliliter (mcg/mL) | Standard Deviation 12.4 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 49 | 56.1 micrograms per milliliter (mcg/mL) | Standard Deviation 22.2 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 85 | 56.6 micrograms per milliliter (mcg/mL) | Standard Deviation 22.7 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 13 | 52.6 micrograms per milliliter (mcg/mL) | Standard Deviation 15 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 2 | 15.8 micrograms per milliliter (mcg/mL) | Standard Deviation 5.5 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 133 | 49.0 micrograms per milliliter (mcg/mL) | Standard Deviation 18.5 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 9 | 52.6 micrograms per milliliter (mcg/mL) | Standard Deviation 15.7 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 73 | 62.9 micrograms per milliliter (mcg/mL) | Standard Deviation 24.9 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 17 | 51.2 micrograms per milliliter (mcg/mL) | Standard Deviation 14.9 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 1 | NA micrograms per milliliter (mcg/mL) | — |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 41 | 54.8 micrograms per milliliter (mcg/mL) | Standard Deviation 23.4 |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 7 | 53.6 micrograms per milliliter (mcg/mL) | Standard Deviation 14.3 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 7 | 54.9 micrograms per milliliter (mcg/mL) | Standard Deviation 9.2 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 1 | NA micrograms per milliliter (mcg/mL) | — |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 2 | 18.3 micrograms per milliliter (mcg/mL) | Standard Deviation 6.5 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 3 | 32.7 micrograms per milliliter (mcg/mL) | Standard Deviation 13 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 4 | 49.0 micrograms per milliliter (mcg/mL) | Standard Deviation 13.5 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 5 | 59.1 micrograms per milliliter (mcg/mL) | Standard Deviation 14.6 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 9 | 53.7 micrograms per milliliter (mcg/mL) | Standard Deviation 13.8 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 13 | 53.4 micrograms per milliliter (mcg/mL) | Standard Deviation 14 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 17 | 57.5 micrograms per milliliter (mcg/mL) | Standard Deviation 16.9 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 21 | 55.0 micrograms per milliliter (mcg/mL) | Standard Deviation 13.7 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 25 | 52.8 micrograms per milliliter (mcg/mL) | Standard Deviation 14.1 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 33 | 57.1 micrograms per milliliter (mcg/mL) | Standard Deviation 15.2 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 41 | 63.3 micrograms per milliliter (mcg/mL) | Standard Deviation 19.4 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 49 | 55.1 micrograms per milliliter (mcg/mL) | Standard Deviation 18.7 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 61 | 53.2 micrograms per milliliter (mcg/mL) | Standard Deviation 13.8 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 73 | 51.9 micrograms per milliliter (mcg/mL) | Standard Deviation 13 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 85 | 50.9 micrograms per milliliter (mcg/mL) | Standard Deviation 12.5 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 97 | 53.8 micrograms per milliliter (mcg/mL) | Standard Deviation 16.9 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 109 | 49.3 micrograms per milliliter (mcg/mL) | Standard Deviation 12.8 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 121 | 53.1 micrograms per milliliter (mcg/mL) | Standard Deviation 5 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 133 | 52.0 micrograms per milliliter (mcg/mL) | — |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 145 | 49.5 micrograms per milliliter (mcg/mL) | Standard Deviation 10.3 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 157 | 55.4 micrograms per milliliter (mcg/mL) | Standard Deviation 19.2 |
| Arm C: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 169 | 50.8 micrograms per milliliter (mcg/mL) | — |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 109 | 46.7 micrograms per milliliter (mcg/mL) | Standard Deviation 17.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 41 | 52.0 micrograms per milliliter (mcg/mL) | Standard Deviation 21.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 33 | 52.7 micrograms per milliliter (mcg/mL) | Standard Deviation 17.5 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 25 | 51.2 micrograms per milliliter (mcg/mL) | Standard Deviation 17.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 157 | 55.3 micrograms per milliliter (mcg/mL) | Standard Deviation 16.7 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 121 | 48.5 micrograms per milliliter (mcg/mL) | Standard Deviation 19.7 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 21 | 51.1 micrograms per milliliter (mcg/mL) | Standard Deviation 16.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 17 | 51.0 micrograms per milliliter (mcg/mL) | Standard Deviation 15.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 13 | 50.5 micrograms per milliliter (mcg/mL) | Standard Deviation 14.7 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 2 | 17.1 micrograms per milliliter (mcg/mL) | Standard Deviation 6.6 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 133 | 49.8 micrograms per milliliter (mcg/mL) | Standard Deviation 18.8 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 9 | 51.5 micrograms per milliliter (mcg/mL) | Standard Deviation 14.7 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 7 | 53.4 micrograms per milliliter (mcg/mL) | Standard Deviation 14.9 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 5 | 54.1 micrograms per milliliter (mcg/mL) | Standard Deviation 14 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 1 | NA micrograms per milliliter (mcg/mL) | — |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 145 | 47.4 micrograms per milliliter (mcg/mL) | Standard Deviation 17.4 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 4 | 44.9 micrograms per milliliter (mcg/mL) | Standard Deviation 13.2 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 85 | 54.5 micrograms per milliliter (mcg/mL) | Standard Deviation 22.7 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 3 | 31.9 micrograms per milliliter (mcg/mL) | Standard Deviation 8.8 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 97 | 51.3 micrograms per milliliter (mcg/mL) | Standard Deviation 19.9 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 73 | 57.1 micrograms per milliliter (mcg/mL) | Standard Deviation 22 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 61 | 56.0 micrograms per milliliter (mcg/mL) | Standard Deviation 24.8 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 49 | 53.3 micrograms per milliliter (mcg/mL) | Standard Deviation 20.5 |
| All Participants: 1.5 mg/kg Emicizumab QW | Plasma Trough Concentrations of Emicizumab at Specified Timepoints | Week 169 | 52.5 micrograms per milliliter (mcg/mL) | Standard Deviation 18.7 |
Secondary
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale
Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms severe and serious are not synonymous; severity and seriousness were independently assessed for each AE. For participants whose emicizumab dose was up-titrated, only data before up-titration is included. aPCC = activated prothrombin complex concentrate; Hypersens.= hypersensitivity
Time frame: From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks)
Population: Safety Population: All treated participants grouped by their assigned treatment. For Arm B, data collected while receiving episodic bypassing agents (no prophyalxis) for the first 24 weeks and 1.5 mg/kg emicizumab QW after Week 24 are reported separately under 'Arm B (Control): No Prophylaxis' and 'Arm B (Emi): 1.5 mg/kg Emicizumab QW', respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Local Injection Site Reaction | 9 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TMA Event Related to aPCC and Emicizumab | 1 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Withdrawal from Treatment | 2 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thromboembolic Event (TE) | 1 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TE Event Related to aPCC and Emicizumab | 1 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Serious AE | 10 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thrombotic Microangiopathy (TMA) | 1 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Dose Mod./Interruption | 1 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Any Adverse Event (AE) | 34 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE with Fatal Outcome | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Related AE | 15 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Systemic Hypersens./Anaphylac(tic/toid) Reaction | 0 Participants |
| Arm A: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Grade ≥3 AE | 10 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TMA Event Related to aPCC and Emicizumab | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE with Fatal Outcome | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Local Injection Site Reaction | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Related AE | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Any Adverse Event (AE) | 9 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thromboembolic Event (TE) | 1 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Serious AE | 4 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TE Event Related to aPCC and Emicizumab | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Grade ≥3 AE | 4 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Withdrawal from Treatment | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thrombotic Microangiopathy (TMA) | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Dose Mod./Interruption | 0 Participants |
| Arm B (Control): No Prophylaxis | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Systemic Hypersens./Anaphylac(tic/toid) Reaction | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Related AE | 4 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Any Adverse Event (AE) | 15 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE with Fatal Outcome | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Serious AE | 4 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Withdrawal from Treatment | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Dose Mod./Interruption | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Grade ≥3 AE | 3 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Local Injection Site Reaction | 3 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Systemic Hypersens./Anaphylac(tic/toid) Reaction | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thrombotic Microangiopathy (TMA) | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TMA Event Related to aPCC and Emicizumab | 0 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thromboembolic Event (TE) | 1 Participants |
| Arm B (Emi): 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TE Event Related to aPCC and Emicizumab | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Withdrawal from Treatment | 1 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TMA Event Related to aPCC and Emicizumab | 2 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Any Adverse Event (AE) | 46 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thrombotic Microangiopathy (TMA) | 2 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE with Fatal Outcome | 1 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TE Event Related to aPCC and Emicizumab | 1 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thromboembolic Event (TE) | 1 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Related AE | 13 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Dose Mod./Interruption | 5 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Systemic Hypersens./Anaphylac(tic/toid) Reaction | 0 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Grade ≥3 AE | 7 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Serious AE | 9 Participants |
| Arm C: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Local Injection Site Reaction | 7 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TE Event Related to aPCC and Emicizumab | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Dose Mod./Interruption | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Any Adverse Event (AE) | 9 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Systemic Hypersens./Anaphylac(tic/toid) Reaction | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE Leading to Withdrawal from Treatment | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thrombotic Microangiopathy (TMA) | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Serious AE | 2 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Local Injection Site Reaction | 4 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | TMA Event Related to aPCC and Emicizumab | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | AE with Fatal Outcome | 0 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Related AE | 4 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Grade ≥3 AE | 3 Participants |
| All Participants: 1.5 mg/kg Emicizumab QW | Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale | Thromboembolic Event (TE) | 0 Participants |