Trial Outcomes & Findings for Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures (NCT NCT03361137)

Results Overview

The International Society on Thrombosis and Haemostasis (ISTH) Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with an absence of excessive bleeding at the surgical site indicated by a good to excellent rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "0 to \<10%" or "10% to \< 25%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "No".

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

14 participants

Primary outcome timeframe

Determined at the time of discharge (within approximately 48 hours after surgery)

Results posted on

2021-03-01

Participant Flow

Participant milestones

Participant milestones
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Overall Study STARTED	1	9	1	2	1
Overall Study COMPLETED	0	9	1	2	1
Overall Study NOT COMPLETED	1	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Overall Study Reason not specified	1	0	0	0	0

Baseline Characteristics

Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	Total n=14 Participants Total of all reporting groups
Age, Customized <18 Years Old	1 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	11 Participants n=8 Participants
Age, Customized ≥18 to <65 Years Old	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	14 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	9 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	7 Participants n=8 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants

PRIMARY outcome

Timeframe: Determined at the time of discharge (within approximately 48 hours after surgery)

Population: Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

The International Society on Thrombosis and Haemostasis (ISTH) Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with an absence of excessive bleeding at the surgical site indicated by a good to excellent rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "0 to \<10%" or "10% to \< 25%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "No".

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Percentage of Participants Without Excessive Bleeding at Surgical Sites and Did Not Require BPA/FVIII Use for Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale	—	66.7 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants

PRIMARY outcome

Timeframe: Determined at the time of discharge (within approximately 48 hours after surgery)

Population: Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

The ISTH Assessment of Hemostatic Response for Surgical Procedures scale (see reference PubMed ID:25059285) has four categories, listed here in order of best to worst response: Excellent, Good, Fair, and Poor. The participant's bleeding related to surgery was evaluated by the healthcare professional who performed the procedure using the hemostatic efficacy scale, with excessive bleeding at the surgical site indicated by a fair to poor rating. The endpoint was met when the response to "Intraoperative and/or postoperative blood loss increased over expectation for the non-hemophilic patient determined at the time of discharge" was "25% to \<50%" or "≥50%" AND the response to the question "Did the patient use any bypassing agent (BPA)/factor VIII (FVIII) for the surgery before the discharge?" was "Yes". The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa \[activated\])

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Percentage of Participants With Excessive Bleeding at Surgical Sites and Required BPA/FVIII Use for Treating Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale Total with Excessive Bleeding and Received BPA/FVIII	—	11.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Excessive Bleeding at Surgical Sites and Required BPA/FVIII Use for Treating Bleeding Related to the Surgery, From the Start of Surgery Until Discharge, as Measured by the ISTH Hemostatic Efficacy Scale Treated with 2 mg rFVIIa	—	11.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

PRIMARY outcome

Timeframe: Within 48 hours (if discharged home), and 8 and 28 days after surgery

Population: Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from efficacy analysis.

Post-surgical bleeding information was self-reported by participants (or the participant's legally authorized representative) on the "Bleed and Medication Diary". Bypassing agents (BPAs)/factor VIII (FVIII) used to treat excessive bleeding were also self-reported by participants if it was self-administered. BPAs/FVIII administered by the investigators to treat the bleeding were reported on the "Concomitant Medications" case report form page. The percentage of participants by type and dose of BPA/FVIII used to treat the bleeding is also reported. rFVIIa = recombinant activated human factor VII (eptacog alfa \[activated\])

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Percentage of Participants Who, After Being Discharged From Surgery, Experienced Bleeds That Were Either Related or Unrelated to Surgery and Also Required BPA/FVIII Use Total with Post-surgical Bleeding and Received BPA/FVIII	—	22.2 Percentage of participants	100.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Who, After Being Discharged From Surgery, Experienced Bleeds That Were Either Related or Unrelated to Surgery and Also Required BPA/FVIII Use Treated with 2 mg rFVIIa	—	11.1 Percentage of participants	100.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants Who, After Being Discharged From Surgery, Experienced Bleeds That Were Either Related or Unrelated to Surgery and Also Required BPA/FVIII Use Treated with 5 mg rFVIIa	—	11.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

PRIMARY outcome

Timeframe: Approximately 24 hours prior to surgery

Population: Efficacy Analysis Population: All enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from this analysis.

Enrolled participants received a minimum of four loading doses of emicizumab prior to their surgical procedure. Pharmacokinetic blood samples were obtained at study sites 24 hours before the procedures in order to describe emicizumab plasma concentration on the day of surgery for each of the inhibitor and non-inhibitor cohorts.

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort n=10 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=3 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Emicizumab Plasma Concentration on the Day of Surgery	53.74 micrograms per millilitre (μg/mL) Standard Deviation 28.67	38.40 micrograms per millilitre (μg/mL) Standard Deviation 8.95	—	—	—

PRIMARY outcome

Timeframe: From Baseline up to 30 days after surgery

Population: The analysis included all enrolled participants who provided informed consent.

All adverse events (AEs) that occurred after informed consent was obtained were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v23.0, summarized by severity according to the World Health Organization (WHO) toxicity grading scale (Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death related to AE), and tabulated by body system and preferred term (PT) for individual events within each system organ class (SOC). For each AE, the investigator independently assessed its severity and seriousness, and whether it was considered to be related to the study drug.

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Safety Summary of the Number of Participants With at Least One Adverse Event SAE Leading to Withdrawal from Treatment	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event SAE Leading to Dose Modification/Interruption	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Any Adverse Event (AE)	1 Participants	4 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Serious Adverse Event (SAE)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Related SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event AE Leading to Withdrawal from Treatment	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event AE Leading to Dose Modification/Interruption	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Related AE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Related AE Leading to Withdrawal from Treatment	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Related AE Leading to Dose Modification/Interruption	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Number of Participants With at Least One Adverse Event Grade 3-5 AE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Within 48 hours after surgery, and 8 and 28 days after initial surgery

Population: The analysis included all enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from analysis.

This safety endpoint was a composite endpoint. Surgical complications were entered as adverse events on the case report form page with "Other suspected causes" marked as "Study Surgery or Procedure". This endpoint was met when response to "It required or prolonged inpatient hospitalization" was checked OR response to "Was procedure/surgery performed?" was "Yes".

Outcome measures

Outcome measures
Measure	PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled but did not have surgery. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort n=9 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) with inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort n=2 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for central venous access device (CVAD) removal. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.	PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort n=1 Participants This cohort included participants with Hemophilia A (PwHA) without inhibitors that were enrolled and had surgery for simple dental extraction. All participants received emicizumab via subcutaneous (SC) injection at a loading dose of 3 milligrams of medication per kilogram of body weight (mg/kg) once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly, or by any other approved maintenance regimen, as long as they continued to derive sufficient benefit. Participants must have received all loading doses prior to surgery and planned to continue emicizumab for a minimum of 1 month after surgery.
Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery	—	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

PRIMARY outcome

Timeframe: Within 48 hours after surgery, and 8 and 28 days after initial surgery

Population: The analysis included all enrolled participants who received emicizumab and underwent a minor surgery. One participant with hemophilia A with inhibitors did not undergo surgery and was therefore excluded from analysis.

The percentage of participants who needed blood or blood product transfusions (e.g., platelets, plasma, etc.) during surgery was evaluated.