A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors

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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous 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 bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous 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 bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of all bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated target joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.

Population: All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. The Total Score is derived from the individual scores of all of the domains and it ranges from 0 to 100, with lower scores reflective of better HRQoL.

Time frame: Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Population: All treated participants \<12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL (proxy HRQoL) and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family Life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. A total score is calculated as the sum of all of the items in the scale. The Physical Health domain score ranges from 0 to 100, with lower scores reflective of better physical health.

Time frame: Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Population: All treated participants \<12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. The Physical Health domain assesses hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement). Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Physical Health domain score ranges from 0 to 100, with a lower score reflective of better physical health.

Time frame: Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Population: All treated participants ≥8 to \<12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and ranges from 0 to 100, with a lower score reflective of better health-related quality of life.

Time frame: Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)

Population: All treated participants ≥8 to \<12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.

This is an intra-participant comparison of the percentage of participants by categorized number of all bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

This is an intra-participant comparison of the percentage of participants by categorized number of treated bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A treated bleed is a bleed directly followed by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

This is an intra-participant comparison of the calculated annualized bleeding rate (ABR) for all bleeds (annualized for each participant using the following formula: ABR = \[number of bleeds/number of days during the efficacy period\] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

This is an intra-participant comparison of the calculated ABR for treated bleeds (annualized per participant using the following formula: ABR = \[number of bleeds/number of days during the efficacy period\] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A treated bleed is a bleed directly followed by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for all bleeds (i.e., number of all bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for treated bleeds (i.e., number of treated bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A treated bleed is a bleed directly followed by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.

Population: Treated participants \<12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study

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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous 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 bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous 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 bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated spontaneous bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of treated target joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A joint bleed is defined as a bleed with type reported as joint and with 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. A treated joint bleed is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A treated spontaneous bleed is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A target joint bleed is 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. A treated target joint bleed is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.

Population: All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. All bleeds included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A joint bleed is defined as a bleed with type reported as joint. A target joint bleed is 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.

Time frame: From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Population: All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. All bleeds included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A joint bleed is defined as a bleed with type reported as joint. A target joint bleed is 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.

Time frame: From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Population: All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

The number of bleeds over the efficacy period was shown as a model-based ABR that used a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. All bleeds included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as spontaneous if there is no other known contributing factor such as trauma or procedure/surgery. A joint bleed is defined as a bleed occurring in a joint. A target joint bleed is defined as a joint bleed in a target joint (≥3 bleeds have occurred over the last 24 weeks prior to study entry).

Time frame: From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)

Population: All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were \<12 years of age

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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks

Population: All participants who received at least one dose of emicizumab and were ≥12 years old and weighed \<40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

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 bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks

Population: All participants who received at least one dose of emicizumab and were ≥12 years old and weighed \<40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to 52 weeks

Population: All participants who received at least one dose of emicizumab and were ≥12 years old and weighed \<40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to 52 weeks

Population: All participants who received at least one dose of emicizumab and were ≥12 years old and weighed \<40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.

The number of all bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. 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 was implemented exactly as defined for the treated bleeds outcome measure. 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 Baseline to study completion (up to at least 52 weeks)

Population: All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.

The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for chemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase

Time frame: From Baseline until study completion (up to 188 weeks)

Population: All participants who received at least one dose of emicizumab

The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count

Time frame: From Baseline until study completion (up to 188 weeks)

Population: All participants who received at least one dose of emicizumab

'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.

Time frame: Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)

Population: All participants who received at least one dose of emicizumab

The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, are reported.

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an injection-site reaction on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a local injection-site reaction.

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

Systemic hypersensitivity, anaphylaxis, or anaphylactoid reactions were identified by the investigator using Sampson's criteria, as defined in the protocol. At the primary completion date, one participant had reported two non-serious adverse events (cough and abdominal pain) that were identified as a potential case based on a Standardised MedDRA Queries (SMQ) search for Sampson's criteria. However, after medical review of the case, it was confirmed that this case was not indicative of a systemic hypersensitivity, anaphylaxis, or anaphylactoid reaction.

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

The World Health Organization (WHO) toxicity grading scale was used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable.

Time frame: From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.

Population: All participants who received at least one dose of emicizumab

The number of treated bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. A bleed is considered a treated bleed if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a treatment for bleed, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.

Time frame: From Baseline to study completion (up to at least 52 weeks)

Population: All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.

Pre-dose (trough) plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was 0.1 micrograms per milliliter (μg/mL).

Time frame: Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177

Population: Participants who received at least one dose of emicizumab and had at least one post-dose emicizumab plasma concentration result available