Hemophilia APhase 4NCT03361137
Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
A Phase 4 study testing Emicizumab in people with Hemophilia A, run by Genentech, Inc. at 8 sites in United States.
Trial summary
This Phase IV, multicenter study will evaluate whether participants with Hemophilia A (PwHA) with or without inhibitors receiving emicizumab prophylaxis can safely undergo minor surgical procedures without additional prophylactic bypassing agents (BPA; for participants with inhibitors) or factor VIII (FVIII; for… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Emicizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 8 sitesUnited States
- Study dates
- 28 Jun 2018to 13 Mar 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any age (newborn and older)
- Ability to comply with the study protocol, in the investigator's judgment
- Diagnosis of hemophilia A and current or history of an inhibitor (Bethesda titer ≥0.6 Bethesda units) and currently using bypassing agents (BPAs) for breakthrough bleeds (for PwHA with inhibitors)
- Diagnosis of hemophilia A and no history of an inhibitor (Bethesda titer <0.6 Bethesda units), or a history of an inhibitor that has been tolerized for >5 years and using FVIII for breakthrough bleeds (for PwHA without inhibitors)
- Plan to receive at least 4 loading doses of emicizumab and been adherent to emicizumab prophylaxis by the time of surgery
- Undergoing minor surgery within 60 days of study enrollment. Other minor surgical procedures could be included upon consultation and approval of Medical Monitor, but examples include central venous catheter insertion/removal/replacement, simple dental extractions, colonoscopy, cystoscopy, or endoscopy with biopsy, excisional skin biopsy
- Must plan to continue emicizumab prophylaxis for at least 1 month after surgery
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the study period
Who cannot join
- Diagnosis of a bleeding disorder other than hemophilia A
- Participants who have been tolerized to Factor VIII products (for PwHA with inhibitors)
- Tolerized to FVIII products for <5 years (for PwHA without inhibitors)
- Using FVIII products to treat breakthrough bleeds (for PwHA with inhibitors)
- Treatment with BPAs or FVIII within 24 hours prior to surgical procedure
- Undergoing a major surgical procedure
Show all 15Show fewer
- Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases, including but not limited to diseases such as systemic lupus erythematosus, inflammatory bowel disease, and antiphospholipid syndrome) that may increase the risk of bleeding or thrombosis
- Patients who are at high risk for thrombotic microangiopathy (TMA), e.g., have a previous medical or family history of TMA, in the investigator's judgment
- Would refuse treatment with blood or blood products, if necessary
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
- Pregnant or lactating, or intending to become pregnant during the study; women of childbearing potential must have a negative serum pregnancy test result within 7 days before Study Day 1
- Treatment with any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1; A non-hemophilia-related investigational drug within the last 30 days or 5 half-lives before Study Day 1 (whichever is longer); An investigational drug concurrently
- History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
- Known human immunodeficiency virus (HIV) infection with CD4 count < 200 cells/microlitre within 24 weeks prior to enrollment
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
State University of New York at Buffalo; Women's and Children's Hospital of Buffalo
Buffalo, New York, 14209
Cook Childrens Medical Center
Fort Worth, Texas, 76104
University of Florida
Gainesville, Florida, 32607
Indiana Hemophilia & Thrombosis center
Indianapolis, Indiana, 46260
Childrens Hospital of LA
Los Angeles, California, 90027
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Stanford University/Lucile Packard Children's Hospital
Palo Alto, California, 94304
University of Utah; Division of Gastroenterology/Hepatology
Salt Lake City, Utah, 84132
About this study
Official title: A Phase IV, Multicenter, Single-Arm, Open-Label Study of Emicizumab Prophylaxis in Patients With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
This Phase IV, multicenter study will evaluate whether participants with Hemophilia A (PwHA) with or without inhibitors receiving emicizumab prophylaxis can safely undergo minor surgical procedures without additional prophylactic bypassing agents (BPA; for participants with inhibitors) or factor VIII (FVIII; for participants without inhibitors).
- Conditions
- Hemophilia A
- Being tested
- Emicizumab
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmicizumabDrug
Also called Hemlibra®, ACE910, RG6013
Emicizumab via SC injection at a loading dose 3 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 the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight.
| Study group | Role | What they receive |
|---|---|---|
| PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort | Experimental | 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. Receives: Drug: Emicizumab |
| PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort | Experimental | 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. Receives: Drug: Emicizumab |
| PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort | Experimental | 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. Receives: Drug: Emicizumab |
| PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort | Experimental | 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. Receives: Drug: Emicizumab |
| PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort | Experimental | 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. Receives: Drug: Emicizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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".
Measured: Determined at the time of discharge (within approximately 48 hours 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
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])
Measured: Determined at the time of discharge (within approximately 48 hours 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
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])
Measured: Within 48 hours (if discharged home), and 8 and 28 days after surgery
Emicizumab Plasma Concentration on the Day of Surgery
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.
Measured: Approximately 24 hours prior to surgery
Safety Summary of the Number of Participants With at Least One Adverse Event
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.
Measured: From Baseline up to 30 days after surgery
Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery
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".
Measured: Within 48 hours after surgery, and 8 and 28 days after initial surgery
Percentage of Participants Who Needed Blood/Blood Product Transfusions During Surgery
The percentage of participants who needed blood or blood product transfusions (e.g., platelets, plasma, etc.) during surgery was evaluated.
Measured: Within 48 hours after surgery, and 8 and 28 days after initial surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2017
- Study start28 Jun 2018
- Primary completion13 Mar 2020
- Study completion13 Mar 2020
Why it stopped: The Sponsor decided to terminate the study early for several reasons (low enrollment, limited variety of surgery types, and available scientific data).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03361137
- Sponsor's protocol ID
- ML39791
- Status last verified
- Feb 2021
- First submitted
- 20 Nov 2017
- Last updated
- 1 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014 Nov;12(11):1935-9. doi: 10.1111/jth.12672. Epub 2014 Sep 3. No abstract available.
PubMed 25059285
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Multicenter, Single-Arm, Open-Label Study of Emicizumab Prophylaxis in Patients With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
- ClinicalTrials.gov ID
- NCT03361137
- Acronym / sponsor ID
- ML39791
- Conditions
- Hemophilia A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor decided to terminate the study early for several reasons (low enrollment, limited variety of surgery types, and available scientific data).
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Jun 2018 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 13 Mar 2020 (actual)
- First posted
- 4 Dec 2017 (actual)
- Results
- Posted 1 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase IV, multicenter study will evaluate whether participants with Hemophilia A (PwHA) with or without inhibitors receiving emicizumab prophylaxis can safely undergo minor surgical procedures without additional prophylactic bypassing agents (BPA; for participants with inhibitors) or factor VIII (FVIII; for participants without inhibitors).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort | Experimental | Drug: EmicizumabThis 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 | Experimental | Drug: EmicizumabThis 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 | Experimental | Drug: EmicizumabThis 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 | Experimental | Drug: EmicizumabThis 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 | Experimental | Drug: EmicizumabThis 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Any age (newborn and older)
- Ability to comply with the study protocol, in the investigator's judgment
- Diagnosis of hemophilia A and current or history of an inhibitor (Bethesda titer ≥0.6 Bethesda units) and currently using bypassing agents (BPAs) for breakthrough bleeds (for PwHA with inhibitors)
- Diagnosis of hemophilia A and no history of an inhibitor (Bethesda titer <0.6 Bethesda units), or a history of an inhibitor that has been tolerized for >5 years and using FVIII for breakthrough bleeds (for PwHA without inhibitors)
- Plan to receive at least 4 loading doses of emicizumab and been adherent to emicizumab prophylaxis by the time of surgery
Key exclusion criteria (15 listed)
- Diagnosis of a bleeding disorder other than hemophilia A
- Participants who have been tolerized to Factor VIII products (for PwHA with inhibitors)
- Tolerized to FVIII products for <5 years (for PwHA without inhibitors)
- Using FVIII products to treat breakthrough bleeds (for PwHA with inhibitors)
- Treatment with BPAs or FVIII within 24 hours prior to surgical procedure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmicizumabAlso: Hemlibra®, ACE910, RG6013Emicizumab via SC injection at a loading dose 3 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 the participant continues to derive sufficient benefit. Dosing was to be adjusted if the participant had a significant change in body weight. | Drug | PwHA With Inhibitors, Emicizumab: CVAD Removal Cohort, PwHA With Inhibitors, Emicizumab: Simple Dental Extraction Cohort, PwHA With Inhibitors, Emicizumab: Surgery Not Performed Cohort, PwHA Without Inhibitors, Emicizumab: CVAD Removal Cohort, PwHA Without Inhibitors, Emicizumab: Simple Dental Extraction Cohort |
Primary outcome
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
Time frame: Determined at the time of discharge (within approximately 48 hours after surgery)
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".
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
Time frame: Determined at the time of discharge (within approximately 48 hours after surgery)
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])
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
Time frame: Within 48 hours (if discharged home), and 8 and 28 days after surgery
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])
Emicizumab Plasma Concentration on the Day of Surgery
Time frame: Approximately 24 hours prior to surgery
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.
Safety Summary of the Number of Participants With at Least One Adverse Event
Time frame: From Baseline up to 30 days after surgery
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.
Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery
Time frame: Within 48 hours after surgery, and 8 and 28 days after initial surgery
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".
Percentage of Participants Who Needed Blood/Blood Product Transfusions During Surgery
Time frame: Within 48 hours after surgery, and 8 and 28 days after initial surgery
The percentage of participants who needed blood or blood product transfusions (e.g., platelets, plasma, etc.) during surgery was evaluated.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25059285Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014 Nov;12(11):1935-9. doi: 10.1111/jth.12672. Epub 2014 Sep 3. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Emicizumab in people with Hemophilia A, run by Genentech, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Determined at the time of discharge (within approximately 48 hours after surgery)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03361137, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2021.