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

NCT ID: NCT03361137

Last Updated: 2021-03-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-28
• Study Completion Date: 2020-03-13

Brief 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 participants without inhibitors).

Conditions

Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

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.

Interventions

Emicizumab

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.

Intervention Type: DRUG

Other Intervention Names

Hemlibra®; ACE910; RG6013

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Childrens Hospital of LA

Los Angeles, California, United States

Stanford University/Lucile Packard Children's Hospital

Palo Alto, California, United States

University of Florida

Gainesville, Florida, United States

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

State University of New York at Buffalo; Women's and Children's Hospital of Buffalo

Buffalo, New York, United States

Cook Childrens Medical Center

Fort Worth, Texas, United States

University of Utah; Division of Gastroenterology/Hepatology

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25059285 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ML39791

Identifier Type: -

Identifier Source: org_study_id