Clinical trial NCT03361137: Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hemophilia A
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-04
Enrollment: 14
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
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
timeFrame: Determined at the time of discharge (within approximately 48 hours after surgery)
measure: 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
timeFrame: Determined at the time of discharge (within approximately 48 hours after surgery)
measure: 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
timeFrame: Within 48 hours (if discharged home), and 8 and 28 days after surgery
measure: Emicizumab Plasma Concentration on the Day of Surgery
timeFrame: Approximately 24 hours prior to surgery
measure: Safety Summary of the Number of Participants With at Least One Adverse Event
timeFrame: From Baseline up to 30 days after surgery
measure: Percentage of Participants With Surgical Complications Requiring Hospitalization or Return to Surgery
timeFrame: Within 48 hours after surgery, and 8 and 28 days after initial surgery
measure: Percentage of Participants Who Needed Blood/Blood Product Transfusions During Surgery
timeFrame: Within 48 hours after surgery, and 8 and 28 days after initial surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of LA
state: California
city: Palo Alto
country: United States
facility: Stanford University/Lucile Packard Children's Hospital
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis center
state: Indiana
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: State University of New York at Buffalo; Women's and Children's Hospital of Buffalo
state: New York
city: Fort Worth
country: United States
facility: Cook Childrens Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah; Division of Gastroenterology/Hepatology
state: Utah
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.