A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Emicizumab in Participants With Mild or Moderate Hemophilia A Without FVIII Inhibitors

Phase 3

Active, not recruiting

Conditions: Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor
Mild Hereditary Factor VIII Deficiency Disease Without Inhibitor
Hemophilia A

Interventions: Drug: Emicizumab

Registration Number: NCT04158648

Lead Sponsor: Hoffmann-La Roche

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 73

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Emicizumab	Emicizumab	Participants with mild and moderate hemophilia A without factor VIII (FVIII) inhibitors will be enrolled to receive the emicizumab loading dose regimen followed by the participant's preference of one of 3 maintenance dose regimens.

Primary Outcome Measures

Name	Time	Method
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 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 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.
Median Calculated 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 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.

Secondary Outcome Measures

Name	Time	Method
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Treatment Burden Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Caregivers: Change From Baseline in the Treatment Burden Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Change From Baseline in Respiratory Rate Over Time	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)
Model-Based Annualized Bleed Rate 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 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.
Median Calculated Annualized Bleed Rate 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 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.
Model-Based Annualized Bleed Rate 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 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.
Mean Calculated Annualized Bleed Rate 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 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.
Median Calculated Annualized Bleed Rate 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 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.
Model-Based Annualized Bleed Rate 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 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.
Mean Calculated Annualized Bleed Rate 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 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.
CATCH Questionnaire for Adult Participants: Change From Baseline in the Work Impact Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Change From Baseline in the Preoccupation Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Mean Calculated Annualized Bleed Rate 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 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.
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.
CATCH Questionnaire for Adult Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Scores Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Scores Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Median Calculated Annualized Bleed Rate 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 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.
Model-Based 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 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.
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.
CATCH Questionnaire for Adult Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Scores Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Change From Baseline in the Treatment Burden Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain in Target Joints Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain on Average Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the School Impact Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Preoccupation Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Caregivers: Change From Baseline in the Preoccupation Domain Score Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
Hemophilia Joint Health Scores Over Time	Days -7 to -1, Weeks 25, 49, and every 24 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the MBQ Total Score Over Time	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)
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Heaviness Subscale Score Over Time	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)
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Irregularity Subscale Score Over Time	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)
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time	Baseline (Week 1), Weeks 13, 25, 37 and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)	CATCH = Comprehensive Assessment Tool of Challenges in Hemophilia
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.
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.
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).
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Quality of Life Subscale Score Over Time	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)
Number of Participants With at Least One Thromboembolic Event	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
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.
Number of Participants With Adverse Events Leading to Study Drug Discontinuation	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Number of Participants With at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Change From Baseline in Diastolic Blood Pressure Over Time	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)
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Pain Subscale Score Over Time	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)
Menstruation Diary With the Pictorial Blood Assessment Chart (PBAC) for Female Participants of Childbearing Potential: PBAC Scores Over Time	Baseline (Day 1) and monthly (on days of menstruation) until Study Completion (up to approximately 48 months)
Number of Participants With at Least One Adverse Event by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Number of Participants With at Least One Laboratory Abnormality	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)	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.
Change From Baseline in Body Temperature Over Time	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)
Change From Baseline in Systolic Blood Pressure Over Time	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)
Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG)	Baseline, Weeks 5, 25, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
Number of Participants With at Least One Event of Thrombotic Microangiopathy	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Number of Participants With at Least One Injection-Site Reaction by Severity, According to the WHO Toxicity Grading Scale	From Screening (Day -28 to -1) to Study Completion/Discontinuation Visit (up to approximately 48 months)
Change From Baseline in Pulse Rate Over Time	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)
Change From Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcB, QTcF, RR, PR, and QRS Intervals	Baseline, Weeks 5, 25, and 49, and every 12 weeks thereafter until Study Completion/Discontinuation Visit (up to approximately 48 months)
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, and 49, and every 12 weeks thereafter until study completion/discontinuation (up to approximately 48 months)
Number of Participants With Anti-Drug Antibodies Against Emicizumab at Baseline and Post-Baseline	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)
Number of Participants Who Develop Anti-FVIII Inhibitors Over Time	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)

Trial Locations

Locations (22): Hospital Universitario Virgen del Rocio
🇪🇸
Sevilla, Spain
Cardiff and Vale NHS Trust
🇬🇧
Cardiff, United Kingdom
Royal Free Hospital
🇬🇧
London, United Kingdom
Hopital Cardio-vasculaire Louis Pradel
🇫🇷
Bron, France
CH de Bicetre
🇫🇷
Le Kremlin Bicetre, France
Universitätsklinikum Bonn
🇩🇪
Bonn, Germany
Klinikum der Universität München, Campus Innenstadt
🇩🇪
München, Germany
Instytut Hematologii i Transfuzjologii
🇵🇱
Warsaw, Poland
Charlotte Maxeke Johannesburg Hospital
🇿🇦
Johannesburg, South Africa
Hospital Universitario la Paz
🇪🇸
Madrid, Spain
Great Ormond street Hospital for Children NHS Foundation Trust
🇬🇧
London, United Kingdom
Childrens Hospital LA
🇺🇸
Los Angeles, California, United States
Hemophilia of Georgia Center for Bleeding & Clotting Disorders
🇺🇸
Atlanta, Georgia, United States
Indiana Hemophilia & Thrombosis center
🇺🇸
Indianapolis, Indiana, United States
University of Michigan, C.S. Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Washington Institute for Coagulation
🇺🇸
Seattle, Washington, United States
Cliniques Universitaires St-Luc
🇧🇪
Bruxelles, Belgium
UZ Leuven Gasthuisberg
🇧🇪
Leuven, Belgium
Kaye Edmonton Clinic
🇨🇦
Edmonton, Alberta, Canada
Eastern Health - General Hospital
🇨🇦
St. John's, Newfoundland and Labrador, Canada
Groupe Hospitalier Necker Enfants Malades
🇫🇷
Paris, France
Amsterdam UMC Location AMC
🇳🇱
Amsterdam, Netherlands