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Trial record 19 of 43 for:    "Hemophilia" | "Antibodies"

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

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ClinicalTrials.gov Identifier: NCT03361137
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

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).

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: Emicizumab Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 28, 2018
Estimated Primary Completion Date : December 16, 2020
Estimated Study Completion Date : December 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
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.
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

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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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.

  11. 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).

  12. 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).

  13. 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 ]
  14. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03361137


Contacts
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Contact: Reference Study ID: ML39791 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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United States, California
Childrens Hospital of LA Recruiting
Los Angeles, California, United States, 90027
Stanford University/Lucile Packard Children's Hospital Recruiting
Palo Alto, California, United States, 94304
United States, Colorado
University of Colorado Denver, Children's Hospital Withdrawn
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32607
Johns Hopkins All Children's Hospital Not yet recruiting
Saint Petersburg, Florida, United States, 33701
United States, Indiana
Indiana Hemophilia & Thrombosis center Recruiting
Indianapolis, Indiana, United States, 46260
United States, Michigan
University of Michigan, C.S. Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Wayne State University Withdrawn
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hosp Clinics Recruiting
Kansas City, Missouri, United States, 64108
United States, New Jersey
Robert Wood Johnson University Hospital/Rutgers Recruiting
New Brunswick, New Jersey, United States, 08901
Newark Beth Israel Medical Center Recruiting
Newark, New Jersey, United States, 07112
United States, New York
State University of New York at Buffalo; Women's and Children's Hospital of Buffalo Recruiting
Buffalo, New York, United States, 14209
Weill Cornell Medical College, Dept. of Medicine; Division of Hematology/Oncology Recruiting
New York, New York, United States, 10065
United States, North Carolina
Duke University Hospital South Recruiting
Durham, North Carolina, United States, 27710
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hosp of Pittsburgh; Div Hematology/Oncology/BMT Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Cook Childrens Medical Center Recruiting
Fort Worth, Texas, United States, 76104
University of Texas Medical School-Houston Recruiting
Houston, Texas, United States, 77030
United States, Utah
University of Utah; Division of Gastroenterology/Hepatology Recruiting
Salt Lake City, Utah, United States, 84132
United States, Washington
Bloodworks Northwest (formerly Puget Sound Blood Center); Hemophilia Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

Publications:
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03361137     History of Changes
Other Study ID Numbers: ML39791
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Antibodies, Bispecific
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Immunologic Factors
Physiological Effects of Drugs