Hemophilia A, Mild Hereditary Factor VIII Deficiency Disease Without Inhibitor, Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor
Conditions
Keywords
Mild Hemophilia A Without Factor VIII Inhibitors, Moderate Hemophilia A Without Factor VIII Inhibitors
Brief summary
This is a multicenter, open-label, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of emicizumab in participants with mild or moderate hemophilia A without inhibitors against factor VIII (FVIII).
Interventions
DRUGEmicizumab
Four loading doses of emicizumab 3 milligrams per kilogram of body weight (mg/kg) will be administered subcutaneously (SC) once a week (QW) for 4 weeks followed by participant's preference of one of the three following maintenance SC dose regimens: 1.5 mg/kg QW, 3 mg/kg once every 2 weeks (Q2W), or 6 mg/kg once every 4 weeks (Q4W).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diagnosis of mild (FVIII level between \>5% and \<40%) or moderate (FVIII level between ≥1% and ≤5%) congenital Hemophilia A without FVIII inhibitors * Weight ≥3 kilograms (kg) * Need for prophylaxis based on investigator assessment * A negative test for inhibitor (i.e., \<0.6 Bethesda Units per milliliter \[BU/mL\]) within 8 weeks prior to enrollment * No documented inhibitor (i.e., \<0.6 BU/mL), FVIII half-life \<6 hours, or FVIII recovery \<66% in the last 5 years * Documentation of the details of prophylactic or episodic FVIII treatment and of number of bleeding episodes for at least the last 24 weeks prior to enrollment * Adequate hematologic, hepatic, and renal function * For women of childbearing potential: agreement to remain abstinent or use contraception (as defined in the protocol) during the treatment period and for at least 24 weeks after the final dose of study drug
Exclusion criteria
* Inherited or acquired bleeding disorder other than mild or moderate congenital hemophilia A * History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator's judgment * Previous (within the last 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease * Other conditions that may currently increase the risk of bleeding or thrombosis * History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection * Planned surgery during the emicizumab loading dose phase (surgeries in participants on emicizumab from Week 5 onwards are allowed) * Known HIV infection with CD4 counts \<200 cells per microlitre (/μL) * Concomitant disease, condition, significant abnormality on screening evaluation or laboratory tests, or treatment that could interfere with the conduct of the study, or that would in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant * Receipt of any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration with the exception of prior emicizumab prophylaxis; A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; or Any other investigational drug currently being administered or planned to be administered * Inability to comply with the study protocol in the opinion of the investigator * Pregnant or breastfeeding, or intending to become pregnant during the study (women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-Based Annualized Bleed Rate for Treated Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated bleed was 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. |
| Mean Calculated ABR for Treated Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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. |
| Median Calculated ABR for Treated Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Model-Based ABR for All Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of all bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Mean Calculated ABR for All Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Median Calculated ABR for All Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Model-Based ABR for Treated Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Mean Calculated ABR for Treated Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Median Calculated ABR for Treated Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Model-Based ABR for Treated Target Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated target joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Mean Calculated ABR for Treated Target Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Median Calculated ABR for Treated Target Joint Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Model-Based ABR for Treated Spontaneous Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated spontaneous bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| Mean Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| Median Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds | From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks) | The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Bleeds | Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated bleed was 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. |
| Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Bleeds | Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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. |
| Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Bleeds | Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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. |
| Long-term Efficacy of Emicizumab: Model-Based ABR for All Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of all bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Long-term Efficacy of Emicizumab: Mean Calculated ABR for All Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Long-term Efficacy: Median Calculated ABR for All Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself. |
| Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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. |
| Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Target Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated target joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Target Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Target Joint Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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. |
| Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Spontaneous Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated spontaneous bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Spontaneous Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Spontaneous Bleeds | median [range, min-max] efficacy period: 156.07 [24.1-274] weeks | The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/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. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Daily Activity Risk Perception (RP) and Impact Domain Scores Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and Study completion (SC)/Early discontinuation (ED) (up to approximately 274 weeks) | Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the daily activity RP and impact domain has 48 items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing daily activities and higher impact of hemophilia on daily activities. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Social Activity RP and Impact Domain Scores Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the social activity RP and impact domain has 22 items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing social activities and higher impact of hemophilia on social activities. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Recreational Activity RP and Impact Domain Scores Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the recreational activity RP and impact domain has 32 items and a larger bank of additional items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing recreational activities and higher impact of hemophilia on recreational activities. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Work Impact (WI) and College Impact (CI) Domains Score Over Time | WI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks); CI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, work and college impact has 10 items and the items were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated impact of hemophilia on work and college activities. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Preoccupation Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, preoccupation has 10 items which were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia. |
| CATCH Questionnaire for Adult Participants: Change From Baseline in the Treatment Burden Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, treatment burden has 8 items which were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater perceived burden of the hemophilia treatment. |
| CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time | Baseline, Weeks 25, 49, 61, 85, 121, 133, 157 and 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consisting of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question: "Did you get a bleed in the past 7 days?" If the response was yes, participants were asked to rate their pain by selecting the number that best described the pain associated with the bleed. Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain in Target Joints Over Time | Baseline, Weeks 1, 13, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Do you have target joints?" (If yes, please rate your pain by picking the number that best describes your pain in your target joint(s) over the past 7 days). Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time | Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its WORST over the past 7 days". Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least Over Time | Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its LEAST over the past 7 days." Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least on the Average Over Time | Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its average over the past 7 days". Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Daily Activity RP and Impact Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, daily activity RP and impact has 38 items with each item scored on 3 or 4 points ordinal scale. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicating higher perceived risk of having a bleed while doing daily activities and higher impact of hemophilia on daily activities. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, social activity RP and impact has 16 items which were scored on 3 or 4 points ordinal scale. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher perceived risk of having a bleed while doing social activities and higher impact of hemophilia on social activities. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Recreational Activity RP and Impact Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, recreational activity RP \& impact has 34 items + larger bank of additional items. The items were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher perceived risk of having a bleed while doing recreational activities and higher impact of hemophilia on recreational activities. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the School Impact Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, school impact has 11 items and the items were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher impact of hemophilia on school activities. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Preoccupation Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, preoccupation has 3 items which were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia. |
| CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Treatment Burden Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, treatment burden has 7 items which were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept \& applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated lower perceived burden of the hemophilia treatment. |
| CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Hurt Associated With a Bleed Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 85, 97, 109, 121, 133, 145 and 157 | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, pain domain (Hurt) consists of two items, assessed using an 11-point numeric rating scale where 0 = no hurt and 10 = a lot of hurt. The data reported here are from participants who answered the following question "Did you get a bleed in the past 7 days? ( If yes, how much did the bleed hurt?)." Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Hurt at Its Worst Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145,157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, pain domain (Hurt) consists of two items, assessed using an 11-point numeric rating scale where 0 = no hurt and 10 = a lot of hurt. The data reported here are from participants who answered the following question "What is the WORST that your body has hurt over the past 7 days". Data is reported only for categories/timepoints with non-zero values. |
| CATCH Questionnaire for Caregivers: Change From Baseline in the Preoccupation Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on caregivers of pediatric participants (aged \<8 years). The caregiver version has 2 domains (preoccupation and treatment burden). Of this, preoccupation has 13 items with each of the items were scored on 4 or 5 ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia. |
| CATCH Questionnaire for Caregivers: Change From Baseline in the Treatment Burden Domain Score Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | CATCH was used to measure the effect of hemophilia and its treatment on caregivers of pediatric participants (aged \<8 years). The caregiver version has 2 domains (preoccupation and treatment burden). Of this, treatment burden has 8 items which were scored on 4 or 5 ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater perceived burden of the hemophilia treatment. |
| Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Week 17 | The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with subcutaneous (SC) emicizumab, intravenous (IV) factor VIIII (FVIII), or no preference. The 95% confidence intervals were calculated using the Pearson-Clopper method. |
| Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Week 17 | The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the caregiver's preference for their child's treatment with subcutaneous (SC) emicizumab, intravenous (IV) factor VIIII (FVIII), or no preference. The 95% confidence intervals were calculated using the Pearson-Clopper method. |
| Change From Baseline in Hemophilia Joint Health Scores Over Time | Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks) | The HJHS measures joint health of the joints (knees, ankles, and elbows) most commonly affected by bleeding in hemophilia. The HJHS 2.1 provides joint specific total scores which are added to obtain the sum of joints totals and also a global gait score. These two scores are then added to obtain HJHS total score. The minimum score per joint is 0, the maximum score is 20. In addition, Gait is scored on a scale from 0 to 4 based on the number of skills that are not within the normal limits. The total score is the sum of scores across all six joints plus the gait score (range from 0 to 124, with 0 being normal and 124 being the most severe disease). A higher score indicates worse joint health. |
| Change From Baseline in Mean Daily Peak Activity Duration Over Time | Baseline (Weeks 1-2) and Weeks 13 (Weeks 12-13 period), 25 (Weeks 24-25 period), 37 (Weeks 36-37 period), and 49 (Weeks 48-49 period) | For physical activity assessment, participants ≥5 years of age were instructed to wear the study accelerometry device on the wrist continuously (24 hours/day) every day for the designated 2-week periods during the study. A participant was considered to be compliant with the physical activity assessments if they wore the study device continuously (≥8 hours/day) every day for at least 8 days of each of the designated 2-week periods during the study. If this compliance criterion was not reached at a specific timepoint the participant was not included in the analysis of the designated 2-week periods where compliance was not reached. Daily measurements were averaged over the 14-days timepoint. Activity count was a measure of the acceleration measured by the device. The daily peak activity duration was defined as the sum of moderate to vigorous activity per day (in minutes). |
| Change From Baseline in Mean Daily Step Count Over Time | Baseline (Weeks 1-2) and Weeks 13 (Weeks 12-13), 25 (Weeks 24-25), 37 (Weeks 36-37), and 49 (Weeks 48-49) | For physical activity assessment, participants ≥5 years of age were instructed to wear the study accelerometry device on the wrist continuously (24 hours/day) every day for the designated 2-week periods during the study. A participant was considered to be compliant with the physical activity assessments if they wore the study device continuously (≥8 hours/day) every day for at least 8 days of each of the designated 2-week periods during the study. If this compliance criterion was not reached at a specific timepoint the participant was not included in the analysis of the designated 2-week periods where compliance was not reached. Daily measurements were averaged over the 14-days timepoint. Activity count was a measure of the acceleration measured by the device. |
| Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the MBQ Total Score Over Time | Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and145 | The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The MBQ score ranges from 0 to 75. Higher scores indicate a worse quality of life and more severe symptoms. |
| MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Heaviness Subscale Score Over Time | Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137 (up to approximately 274 weeks) | The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for heaviness subscale ranges from 0 to 29. Higher score indicates more heavy bleeding. |
| MBQ for Female Participants of Childbearing Potential: Change From Baseline in the QoL Subscale Score Over Time | Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145 | The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for QoL subscale ranges from 0 to 37. Higher scores indicate a worse QoL. |
| MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Irregularity Subscale Score Over Time | Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145 | The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for irregularity subscale ranges from 0 to 6. Higher score indicates more irregularity. |
| MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Pain Subscale Score Over Time | Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137 | The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for pain subscale ranges from 0 to 3. Higher score indicates severe pain. |
| Menstruation Diary With the Pictorial Blood Assessment Chart (PBAC) for Female Participants of Childbearing Potential: PBAC Scores Over Time | Baseline and monthly (on days of menstruation) until Study Completion (up to approximately 247 weeks) | The Menstruation Diary used a PBAC, which has shown good correlation with menstrual blood loss. The PBAC is a chart that records the occurrence and size of clots, and the number of episodes of heavy bleeding (flooding), as well as depicts the amount of blood loss during a cycle.The PBAC records pad and tampon use (as either light \[1 point\], medium \[5 points\], or heavy \[10 points\] flow), clots (small \[1 point\] or large \[5 points\]), and flooding episodes (1 point each) which can be recorded as many times as necessary any day of the month. The PBAC is scored from 0 (no bleeding) onwards, with a score of \>100 defining abnormal coagulation and heavy menstrual bleeding (corresponds to \>80ml of blood loss per menstrual cycle). |
| Number of Participants With at Least One Adverse Event by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. As per WHO toxicity grading, Grade 1= mild, 2= moderate, 3=severe, 4=life threatening. |
| Number of Participants With Adverse Events Leading to Study Drug Discontinuation | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. |
| Number of Participants With at Least One Thromboembolic Event | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. The following signs and symptoms were recognized as potential thromboembolism (i.e., dyspnea, chest pain, leg pain, or swelling; or if in the head, headache, numbness in the face, eye pain or swelling, or vision impairment). |
| Number of Participants With at Least One Event of Thrombotic Microangiopathy | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. TMA is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, central nervous system, etc. |
| Number of Participants With at Least One Injection-Site Reaction by Severity, According to the WHO Toxicity Grading Scale | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Injection-site reactions are defined as AEs related that occur within 24 hours after study drug administration and are judged to be related to the study drug injection. Local injection-site reactions included erythema, hematoma, rash, discomfort, pain, and pruritus and were mostly of mild and moderate intensity. As per WHO toxicity grading, Grade 1= mild, 2= moderate, 3=severe, 4=life threatening. |
| Number of Participants With at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event | From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. |
| Number of Participants With at Least One Shifts in Clinical Laboratory Parameters From Baseline WHO Toxicity Scale Grade 0-2 to Post-baseline Grade 3 or 4 | Up to approximately 274 weeks | An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. |
| Number of Participants With at Least One Adverse Events of Changes From Baseline in Vital Signs | Up to approximately 274 weeks | The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab. |
| Change From Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcB, QTcF, RR, PR, and QRS Intervals | Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks) | — |
| Change From Baseline in Heart Rate Over Time, as Measured by ECG | Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks) | — |
| Plasma Trough Concentration (Ctrough) of Emicizumab Over Time | Pre-dose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and 181 (up to approximately 274 weeks) | — |
| Number of Participants With Anti-Drug Antibodies Against Emicizumab at Baseline and Post-Baseline | Baseline, Weeks 5, 13, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 169, 181 and SC/ED (up to approximately 274 weeks) | Participants were considered to be ADA positive if they were ADA negative at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response). The sum of all visits has been reported here. |
| Number of Participants Who Develop Anti-FVIII Inhibitors Over Time | Up to approximately 274 weeks | Central laboratory measurement of anti-FVIII inhibitory antibodies (inhibitors) was performed using a Chromogenic Bethesda Assay (CBA). Participants who develop anti-FVIII inhibitors (titer ≥ 0.6 Bethesda units per milliliter \[BU/mL\]) following study drug administration were summarized. |
Countries
Belgium, Canada, France, Germany, Netherlands, Poland, South Africa, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 73 participants with mild or moderate hemophilia A without inhibitors against Factor VIII (FVIII) took part in the study at 22 investigative sites across 10 countries from 10 February 2020 to 19 December 2025.
Participants by arm
| Arm | Count |
|---|---|
| Emicizumab Participants with mild and moderate hemophilia A without factor VIII (FVIII) inhibitors were enrolled to receive the emicizumab loading dose regimen (emicizumab 3 mg/kg administered subcutaneously \[SC\] QW for 4 weeks) followed by participant preference of one of the following 3 emicizumab SC maintenance dose regimens: 1.5 mg/kg QW, 3 mg/kg Q2W, or 6 mg/kg Q4W. | 73 |
| Total | 73 |
Baseline characteristics
| Characteristic | Emicizumab |
|---|---|
| Age, Continuous | 25.9 Years STANDARD_DEVIATION 17 |
| Age, Customized 12 to <18 Years Old | 14 Participants |
| Age, Customized 18 to <65 Years Old | 41 Participants |
| Age, Customized 2 to <6 Years Old | 5 Participants |
| Age, Customized ≥65 Years Old | 2 Participants |
| Age, Customized 6 to <12 Years Old | 11 Participants |
| Emicizumab Maintenance Dosing Regimen Chosen at Enrollment 1.5 mg/kg Once Every Week (QW) | 25 Participants |
| Emicizumab Maintenance Dosing Regimen Chosen at Enrollment 3 mg/kg Once Every 2 Weeks (Q2W) | 39 Participants |
| Emicizumab Maintenance Dosing Regimen Chosen at Enrollment 6 mg/kg Once Every 4 Weeks (Q4W) | 8 Participants |
| Emicizumab Maintenance Dosing Regimen Chosen at Enrollment Not Assigned (Not Treated) | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Hemophilia A Severity Mild | 21 Participants |
| Hemophilia A Severity Moderate | 52 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 62 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 72 |
| other Total, other adverse events | 55 / 72 |
| serious Total, serious adverse events | 17 / 72 |
Outcome results
Primary
Mean Calculated Annualized Bleed Rate for Treated Bleeds
The number of treated bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emicizumab | Mean Calculated Annualized Bleed Rate for Treated Bleeds | 0.9 Treated bleeds per year |
Primary
Median Calculated Annualized Bleed Rate for Treated Bleeds
The number of treated bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emicizumab | Median Calculated Annualized Bleed Rate for Treated Bleeds | 0.0 Treated bleeds per year |
Primary
Model-Based Annualized Bleed Rate for Treated Bleeds
The number of treated bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated bleed was 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Emicizumab | Model-Based Annualized Bleed Rate for Treated Bleeds | 0.9 Treated bleeds per year |
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Scores Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Preoccupation Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Scores Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Scores Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Treatment Burden Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Change From Baseline in the Work Impact Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain in Target Joints Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain on Average Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Caregivers: Change From Baseline in the Preoccupation Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Caregivers: Change From Baseline in the Treatment Burden Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Preoccupation Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the School Impact Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Treatment Burden Domain Score Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time
CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Time frame: Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Body Temperature Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Diastolic Blood Pressure Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcB, QTcF, RR, PR, and QRS Intervals
Time frame: Baseline, Weeks 5, 25, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)
Time frame: Baseline, Weeks 5, 25, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Mean Daily Peak Activity Duration Over Time
For physical activity assessment, participants ≥5 years of age were instructed to wear the study accelerometry device on the wrist continuously (24 hours/day) every day for the designated 2-week periods during the study. A participant was considered to be compliant with the physical activity assessments if they wore the study device continuously (≥8 hours/day) every day for at least 8 days of each of the designated 2-week periods during the study. If this compliance criterion was not reached at a specific timepoint the participant was not included in the analysis of the designated 2-week periods where compliance was not reached. Daily measurements were averaged over the 14-days timepoint. Activity count was a measure of the acceleration measured by the device. The daily peak activity duration was defined as the sum of moderate to vigorous activity per day (in minutes).
Time frame: Baseline (Weeks 1-2) and Weeks 13 (Weeks 12-13 period), 25 (Weeks 24-25 period), 37 (Weeks 36-37 period), and 49 (Weeks 48-49 period)
Population: The analysis population is treated participants ≥5 years old, further subdivided into analysis groups of ≥5 to \<18 years old and ≥18 years old. The number analyzed for change from baseline (BL) are participants with data that met the compliance criterion at BL and the specified timepoint (i.e., wearing device ≥8 hours/day for ≥8 days per period); if it was not met, they were excluded for each noncompliant timepoint. The overall number analyzed had valid data for at least the BL timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 37 | 14 Minutes per day | Standard Deviation 55 |
| Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 25 | 4 Minutes per day | Standard Deviation 53 |
| Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Baseline (BL) - Value at Visit | 130 Minutes per day | Standard Deviation 56 |
| Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 13 | -2 Minutes per day | Standard Deviation 34 |
| Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 49 | 17 Minutes per day | Standard Deviation 40 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 25 | -4 Minutes per day | Standard Deviation 74 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Baseline (BL) - Value at Visit | 168 Minutes per day | Standard Deviation 66 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 13 | -4 Minutes per day | Standard Deviation 42 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 37 | 17 Minutes per day | Standard Deviation 73 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 49 | 19 Minutes per day | Standard Deviation 51 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 49 | 16 Minutes per day | Standard Deviation 34 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 37 | 12 Minutes per day | Standard Deviation 40 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Baseline (BL) - Value at Visit | 108 Minutes per day | Standard Deviation 35 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 25 | 8 Minutes per day | Standard Deviation 37 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Peak Activity Duration Over Time | Change from BL at Week 13 | -1 Minutes per day | Standard Deviation 29 |
Secondary
Change From Baseline in Mean Daily Step Count Over Time
For physical activity assessment, participants ≥5 years of age were instructed to wear the study accelerometry device on the wrist continuously (24 hours/day) every day for the designated 2-week periods during the study. A participant was considered to be compliant with the physical activity assessments if they wore the study device continuously (≥8 hours/day) every day for at least 8 days of each of the designated 2-week periods during the study. If this compliance criterion was not reached at a specific timepoint the participant was not included in the analysis of the designated 2-week periods where compliance was not reached. Daily measurements were averaged over the 14-days timepoint. Activity count was a measure of the acceleration measured by the device.
Time frame: Baseline (Weeks 1-2) and Weeks 13 (Weeks 12-13), 25 (Weeks 24-25), 37 (Weeks 36-37), and 49 (Weeks 48-49)
Population: The analysis population is treated participants ≥5 years old, further subdivided into analysis groups of ≥5 to \<18 years old and ≥18 years old. The number analyzed for change from baseline (BL) are participants with data that met the compliance criterion at BL and the specified timepoint (i.e., wearing device ≥8 hours/day for ≥8 days per period); if it was not met, they were excluded for each noncompliant timepoint. The overall number analyzed had valid data for at least the BL timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 37 | 767 Step count per day | Standard Deviation 3189 |
| Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 25 | 119 Step count per day | Standard Deviation 2977 |
| Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Baseline (BL) - Value at Visit | 6441 Step count per day | Standard Deviation 2617 |
| Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 13 | 44 Step count per day | Standard Deviation 1846 |
| Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 49 | 1216 Step count per day | Standard Deviation 2440 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 25 | -69 Step count per day | Standard Deviation 4348 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Baseline (BL) - Value at Visit | 6755 Step count per day | Standard Deviation 3168 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 13 | -18 Step count per day | Standard Deviation 2361 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 37 | 1403 Step count per day | Standard Deviation 4544 |
| Participants ≥5 to <18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 49 | 1740 Step count per day | Standard Deviation 3130 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 49 | 919 Step count per day | Standard Deviation 1945 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 37 | 356 Step count per day | Standard Deviation 1852 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Baseline (BL) - Value at Visit | 6263 Step count per day | Standard Deviation 2276 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 25 | 225 Step count per day | Standard Deviation 1901 |
| Participants ≥18 Years Old: Emicizumab | Change From Baseline in Mean Daily Step Count Over Time | Change from BL at Week 13 | 87 Step count per day | Standard Deviation 1423 |
Secondary
Change From Baseline in Pulse Rate Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Respiratory Rate Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Change From Baseline in Systolic Blood Pressure Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Hemophilia Joint Health Scores Over Time
Time frame: Days -7 to -1, Weeks 25, 49, and every 24 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Mean Calculated Annualized Bleed Rate for All Bleeds
The number of all bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As all bleeds comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emicizumab | Mean Calculated Annualized Bleed Rate for All Bleeds | 2.3 All bleeds per year |
Secondary
Mean Calculated Annualized Bleed Rate for Treated Joint Bleeds
The number of treated joint bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as joint based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emicizumab | Mean Calculated Annualized Bleed Rate for Treated Joint Bleeds | 0.2 Treated joint bleeds per year |
Secondary
Mean Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a treatment for bleed) with no other known contributing factor such as trauma or procedure/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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emicizumab | Mean Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds | 0.3 Treated spontaneous bleeds |
Secondary
Mean Calculated Annualized Bleed Rate for Treated Target Joint Bleeds
The number of treated target joint bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Emicizumab | Mean Calculated Annualized Bleed Rate for Treated Target Joint Bleeds | 0.1 Treated target joint bleeds per year |
Secondary
Median Calculated Annualized Bleed Rate for All Bleeds
The number of all bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As all bleeds comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emicizumab | Median Calculated Annualized Bleed Rate for All Bleeds | 1.0 All bleeds per year |
Secondary
Median Calculated Annualized Bleed Rate for Treated Joint Bleeds
The number of treated joint bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as joint based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emicizumab | Median Calculated Annualized Bleed Rate for Treated Joint Bleeds | 0.0 Treated joint bleeds per year |
Secondary
Median Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a treatment for bleed) with no other known contributing factor such as trauma or procedure/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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emicizumab | Median Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds | 0.0 Treated spontaneous bleeds |
Secondary
Median Calculated Annualized Bleed Rate for Treated Target Joint Bleeds
The number of treated target joint bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emicizumab | Median Calculated Annualized Bleed Rate for Treated Target Joint Bleeds | 0.0 Treated target joint bleeds per year |
Secondary
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Heaviness Subscale Score Over Time
Time frame: Baseline (Week 1), Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and every 4 weeks thereafter until Study Completion (up to approximately 48 months)
Secondary
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Irregularity Subscale Score Over Time
Time frame: Baseline (Week 1), Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and every 4 weeks thereafter until Study Completion (up to approximately 48 months)
Secondary
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the MBQ Total Score Over Time
Time frame: Baseline (Week 1), Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and every 4 weeks thereafter until Study Completion (up to approximately 48 months)
Secondary
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Pain Subscale Score Over Time
Time frame: Baseline (Week 1), Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and every 4 weeks thereafter until Study Completion (up to approximately 48 months)
Secondary
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Quality of Life Subscale Score Over Time
Time frame: Baseline (Week 1), Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and every 4 weeks thereafter until Study Completion (up to approximately 48 months)
Secondary
Menstruation Diary With the Pictorial Blood Assessment Chart (PBAC) for Female Participants of Childbearing Potential: PBAC Scores Over Time
Time frame: Baseline (Day 1) and monthly (on days of menstruation) until Study Completion (up to approximately 48 months)
Secondary
Model-Based Annualized Bleed Rate for All Bleeds
The number of all bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As all bleeds comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that 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. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Emicizumab | Model-Based Annualized Bleed Rate for All Bleeds | 2.3 All bleeds per year |
Secondary
Model-Based Annualized Bleed Rate for Treated Joint Bleeds
The number of treated joint bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated joint bleed was defined as a bleed with type reported as joint based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Emicizumab | Model-Based Annualized Bleed Rate for Treated Joint Bleeds | 0.2 Treated joint bleeds per year |
Secondary
Model-Based Annualized Bleed Rate for Treated Spontaneous Bleeds
The number of treated spontaneous bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a treatment for bleed) with no other known contributing factor such as trauma or procedure/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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Emicizumab | Model-Based Annualized Bleed Rate for Treated Spontaneous Bleeds | 0.2 Treated spontaneous bleeds |
Secondary
Model-Based Annualized Bleed Rate for Treated Target Joint Bleeds
The number of treated target joint bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed 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.
Time frame: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Population: The Treated Population comprises all participants who received at least one dose of emicizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Emicizumab | Model-Based Annualized Bleed Rate for Treated Target Joint Bleeds | 0.1 Treated target joint bleeds per year |
Secondary
Number of Participants Who Develop Anti-FVIII Inhibitors Over Time
Time frame: Screening (Day -28 to -1) and Weeks 1, 13, 25, 37, and 49, and every 12 weeks thereafter until study completion/discontinuation (up to approximately 48 months)
Secondary
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With Anti-Drug Antibodies Against Emicizumab at Baseline and Post-Baseline
Time frame: Pre-dose at Baseline (Week 1) and Weeks 5, 13, 25, 33, 41, and 49, and every 12 weeks thereafter until study completion/discontinuation (up to approximately 48 months)
Secondary
Number of Participants With at Least One Adverse Event by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With at Least One Event of Thrombotic Microangiopathy
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With at Least One Injection-Site Reaction by Severity, According to the WHO Toxicity Grading Scale
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With at Least One Laboratory Abnormality
Laboratory parameters for hematology and blood chemistry will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment.
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Number of Participants With at Least One Thromboembolic Event
Time frame: From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Secondary
Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17
The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the caregiver's preference for their child's treatment with subcutaneous (SC) emicizumab, intravenous (IV) factor VIIII (FVIII), or no preference. The 95% confidence intervals were calculated using the Pearson-Clopper method.
Time frame: Week 17
Population: The analysis population included all caregivers of treated participants less than 18 years of age and who provided a response to the survey at Week 17.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emicizumab | Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Prefer the New Study Drug Treatment (Emicizumab SC) | 85.7 Percentage of caregivers |
| Emicizumab | Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Prefer My Child's Old Hemophilia Treatment (IV) | 3.6 Percentage of caregivers |
| Emicizumab | Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Have No Preference | 10.7 Percentage of caregivers |
Secondary
Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17
The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with subcutaneous (SC) emicizumab, intravenous (IV) factor VIIII (FVIII), or no preference. The 95% confidence intervals were calculated using the Pearson-Clopper method.
Time frame: Week 17
Population: The analysis population included all treated participants 12 years of age or older who provided a response to the survey at Week 17.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Emicizumab | Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Have No Preference | 1.9 Percentage of participants |
| Emicizumab | Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Prefer the New Study Drug Treatment (Emicizumab SC) | 96.2 Percentage of participants |
| Emicizumab | Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 | Prefer My Old Hemophilia Treatment (IV) | 1.9 Percentage of participants |
Secondary
Plasma Trough Concentration (Ctrough) of Emicizumab Over Time
Time frame: Pre-dose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, and 49, and every 12 weeks thereafter until study completion/discontinuation (up to approximately 48 months)