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A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors (STASEY)

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ClinicalTrials.gov Identifier: NCT03191799
Recruitment Status : Active, not recruiting
First Posted : June 19, 2017
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and tolerability of emicizumab in participants with congenital hemophilia A who have documented inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12 or older, will be enrolled in this study and are expected to be enrolled at approximately 85 sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the remainder of the 2-year treatment period.

Condition or disease Intervention/treatment Phase
Hemophilia A Drug: Emicizumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 195 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Multicenter Phase IIIB Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Actual Study Start Date : September 5, 2017
Estimated Primary Completion Date : September 4, 2020
Estimated Study Completion Date : September 4, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
Drug Information available for: Emicizumab

Arm Intervention/treatment
Experimental: Emicizumab
Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period
Drug: Emicizumab
Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period
Other Name: RO5534262




Primary Outcome Measures :
  1. Incidence and severity of all adverse events (AEs) including thromboembolic events, microangiopathic hemolytic anemia or TMA (e.g. hemolytic uremic syndrome), systemic hypersensitivity, anaphylaxis, and anaphylactoid events [ Time Frame: Up to approximately 2 years ]
    Incidence and severity of AEs will be monitored throughout the study to assess the safety and tolerability of emcizumab.


Secondary Outcome Measures :
  1. Numbers of bleeds over time [ Time Frame: Up to approximately 2 years ]
    To evaluate the efficacy of prophylactic administration of emicizumab, the number of bleeds over time will be recorded for all of the enrolled participants. The final analysis will be conducted when all participants have completed 2 years of treatment or have withdrawn, whichever occurs sooner. Participants, or their legally authorized representative, will be asked to report bleed information, including site and type of bleed, time of each individual bleed (day, start and stop time), and treatment for bleed.

  2. Hemophilia Adult Quality of Life Questionnaire (Haem-A-QoL) (>= 18 y) [ Time Frame: Up to approximately 2 years ]
    The Haem-A-QoL (>= 18 y) was designed for adult participants with hemophilia. It comprises 10 dimensions (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, and partnerships and sexuality).

  3. Hemophilia Quality of Life Short Form (Haemo-QoL-SF) (12-17 y) [ Time Frame: Up to approximately 2 years ]
    The Haemo-QoL-SF (12-17 y) was designed as a series of age-related questionnaires to measure HRQoL in children and adolescents with hemophilia. This version covers nine dimensions considered relevant for children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports, dealing with hemophilia, and treatment).

  4. EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) [ Time Frame: Up to approximately 2 years ]
    The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations.

  5. Participant preference for the emicizumab regimen compared with the previous regimen, as measured by the EmiPref questionnaire [ Time Frame: Month 3 ]
    The EmiPref questionnaire asks participants to specify the treatment they would prefer to continue to receive after receiving treatment with their previous episodic or prophylactic regimen and subcutaneous (SC) emicizumab.

  6. Incidence and clinical significance of anti-emicizumab antibodies [ Time Frame: Up to approximately 2 years ]
    Immunogenicity will be monitored by incidence and clinical significance of antibodies to emicizumab. For the assessment of anti-FVIII antibodies, functional assays for FVIII inhibitors that utilize a clotting readout (classic Bethesda or Nijmegen assay) cannot be used for participants on emicizumab therapy as emicizumab drives clotting even in the presence of FVIII inhibitors, causing a false-negative test result. After the first dose, local measurement of FVIII inhibitors, if indicated, requires use of an enzyme linked immunosorbent assay- (ELISA-) based test or a chromogenic Bethesda assay. At the discretion of the local investigator, any additional urgent request to assess FVIII inhibitors will need to be sent to a central laboratory.

  7. Ctrough of emicizumab [ Time Frame: Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years) ]
    Ctrough is a measure of plasma concentration of a study drug at the end of of the dosage interval.

  8. Clearance of emicizumab [ Time Frame: Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years) ]
    Clearance is the rate at which a study drug is removed from the body.

  9. Volume of distribution of emicizumab [ Time Frame: Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years) ]
    Volume of distribution is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.

  10. Area under the plasma drug concentration-time curve (AUC) of emicizumab [ Time Frame: Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years) ]
    AUC reflects the actual body exposure of a study drug after dosing.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • As per investigator's judgement, a willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an electronic device or paper
  • Aged 12 years or older at the time of informed consent
  • Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
  • Documented treatment with bypassing agents or FVIII concentrates in the last 6 months (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day before starting emicizumab
  • Adequate hematologic, hepatic, and renal function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of <1% per year during the treatment period and for at least five elimination half-lives (24 weeks) after the last dose of emicizumab

Exclusion Criteria:

  • Inherited or acquired bleeding disorder other than hemophilia A
  • Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to enrollment). Patients receiving ITI therapy will be eligible following the completion of a 72-hour washout period prior to the first emicizumab administration
  • History of illicit drug or alcohol abuse within 12 months prior to screening, as per the investigator's judgment
  • High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), as per the investigator's judgment
  • Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
  • Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
  • History of clinically significant hypersensitivity reaction associated with monoclonal antibody therapies or components of the emicizumab injection
  • Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/μL within 6 months prior to screening
  • Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
  • Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
  • Receipt of: Emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within five half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or five half-lives, whichever is shorter; or, Any concurrent investigational drug.
  • Pregnancy or lactation, or intent to become pregnant during the study
  • Positive serum pregnancy test result within 7 days prior to initiation of emicizumab (females only)

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): NCT03191799


  Show 76 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03191799     History of Changes
Other Study ID Numbers: MO39129
2016-004366-25 ( EudraCT Number )
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Antibodies, Bispecific
Coagulants
Immunologic Factors
Physiological Effects of Drugs