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Trial record 22 of 46 for:    "Hemophilia" | "Antibodies"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03361137
Recruitment Status : Active, not recruiting
First Posted : December 4, 2017
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE November 20, 2017
First Posted Date  ICMJE December 4, 2017
Last Update Posted Date April 1, 2020
Actual Study Start Date  ICMJE June 28, 2018
Estimated Primary Completion Date December 16, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • 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. Participants with a rating of Good or Excellent on this scale will have met the criteria.
  • 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 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. Participants with a rating of Fair or Poor on this scale will have met the criteria.
  • Number of Doses of BPAs/FVIII Used Per Bleed, From the Start of Surgery Until Discharge, in Participants With Excessive Bleeding at Surgical Sites That Required BPA/FVIII Use for Treating Bleeding Related to the Surgery [ Time Frame: Determined at the time of discharge (within approximately 48 hours after surgery) ]
  • Total Dose of BPAs/FVIII Used Per Bleed, From the Start of Surgery Until Discharge, in Participants With Excessive Bleeding at Surgical Sites That Required BPA/FVIII Use for Treating Bleeding Related to the Surgery [ Time Frame: Determined at the time of discharge (within approximately 48 hours after surgery) ]
  • Frequency of BPAs/FVIII Used Per Bleed, From the Start of Surgery Until Discharge, in Participants With Excessive Bleeding at Surgical Sites That Required BPA/FVIII Use for Treating Bleeding Related to the Surgery [ Time Frame: 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 [ Time Frame: Within 48 hours (if discharged home), and 8 and 28 days after surgery ]
  • Number of Doses of BPAs/FVIII Used Per Bleed in 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: From discharge up to 30 days after surgery ]
  • Total Dose of BPAs/FVIII Used Per Bleed in 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: From discharge up to 30 days after surgery ]
  • Frequency of BPAs/FVIII Used Per Bleed in 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: From discharge up to 30 days after surgery ]
  • Number of Participants with at Least One Adverse Event [ Time Frame: From Baseline up to 30 days after surgery ]
    This includes all non-serious and serious adverse events.
  • Number of Participants with Serious Adverse Events by Severity, as Determined by World Health Organization (WHO) Toxicity Grading Scale [ Time Frame: From Baseline up to 30 days after surgery ]
    WHO Toxicity Grading Scale has Grades 1-4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening).
  • Number of Participants with Adverse Events of Special Interest by Severity, as Determined by WHO Toxicity Grading Scale [ Time Frame: From Baseline up to 30 days after surgery ]
    WHO Toxicity Grading Scale has Grades 1-4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening).
  • 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 ]
  • Percentage of Participants who Need Blood/Blood Product Transfusions During Surgery [ Time Frame: Within 48 hours after surgery, and 8 and 28 days after initial surgery ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2017)
  • Percentage of Participants Without Excessive Bleeding at Surgical Sites and no Additional BPA, as Measured by the ISTH Assessment of Hemostatic Response for Surgical Procedures 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. Participants with a rating of Good or Excellent on this scale will have met the criteria.
  • Percentage of Participants With Excessive Bleeding at Surgical Sites and Required BPA for Treating Excessive Bleeding [ Time Frame: Determined at the time of discharge (within approximately 48 hours after surgery) ]
  • Percentage of Participants who had Bleeding Related and Unrelated to Surgery who Required BPA for Bleeding [ Time Frame: Within 48 hours (if discharged home), and 8 and 28 days after surgery ]
  • Percentage of Participants with Adverse Events (AEs), Serious AEs, and AEs of Special Interest [ Time Frame: Up to 30 days after surgery ]
  • 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 ]
  • Percentage of Participants who Need Blood/Blood Product Transfusions During Surgery [ Time Frame: Within 48 hours after surgery, and 8 and 28 days after initial surgery ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Emicizumab Prophylaxis in Participants With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical Procedures
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE Drug: 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.
Other Names:
  • Hemlibra®
  • ACE910
  • RG6013
Study Arms  ICMJE
  • Experimental: Cohort 1 - PwHA With Inhibitors: Emicizumab Prophylaxis
    All eligible participants with Hemophilia A (PwHA) with inhibitors will receive 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 continue to derive sufficient benefit. Participants must have received all loading doses prior to surgery and plan to continue emicizumab for a minimum of 1 month after surgery. Dosing should be adjusted if the participant has a significant change in body weight.
    Intervention: Drug: Emicizumab
  • Experimental: Cohort 2 - PwHA Without Inhibitors: Emicizumab Prophylaxis
    All eligible participants with Hemophilia A (PwHA) without inhibitors will receive emicizumab via SC injection at a loading dose of 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 they continue to derive sufficient benefit. Participants must have received all loading doses prior to surgery and plan to continue emicizumab for a minimum of 1 month after surgery. Dosing should be adjusted if the participant has a significant change in body weight.
    Intervention: Drug: Emicizumab
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 31, 2020)
14
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2017)
30
Estimated Study Completion Date  ICMJE December 16, 2020
Estimated Primary Completion Date December 16, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03361137
Other Study ID Numbers  ICMJE ML39791
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP