Hemophilia A with Inhibitors MedDRA version: 19.1 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850 MedDRA version: 19.1 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850
Conditions
Interventions
Product Name: ACE910
Product Code: Ro 553-4262/F03
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EMICIZUMAB
Current Sponsor code: Ro 553-4262/F03
Other descriptive name: RO5534262
C
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Aged 12 years or older at the time of informed consent - Body weight >=40 kg at the time of screening - Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (i.e., >= 5 Bethesda Units) - Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks - >= 6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing agent regimen) or >= 2 bleeds in the last 24 weeks prior to screening (if on a prophylactic bypassing agent regimen) - Adequate hematologic function - Adequate hepatic function - Adequate renal function - For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective contraceptive methods Are the trial subjects under 18? yes Number of subjects for this age range: 7 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 91 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: - Inherited or acquired bleeding disorder other than hemophilia A - Ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with FVIII with the exception of patients who have received a treatment regimen of FVIII prophylaxis with concurrent bypassing agent prophylaxis - History of illicit drug or alcohol abuse within 48 weeks prior to screening, in 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 - Previous or concurrent autoimmune or connective tissue disease - History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection - Known HIV infection with CD4 count =< 200 cells/microliter within 24 weeks 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 - Patients who are at high risk for thrombotic microangiopathy TMA (TMA; e.g., have a previous medical or family history of TMA), in the investigator's judgment - 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 - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study - Receipt of • Emicizumab in a prior investigational study • An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration • A non-hemophilia-related investigational drug within last 30 days or 5 half lives, whichever is shorter • An investigational drug concurrently - Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority) - Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient - Pregnancy or lactation, or intent to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of prophylactic EMICIZUMAB compared with no prophylaxis in patients with hemophilia A with inhibitors on the basis of number of bleeds over time;Secondary Objective: Arms A and B o To evaluate - number of all bleeds (treated and not treated) over time - number of spontaneous bleeds over time - number of joint bleeds over time - number of target joint bleeds over time - health-related quality of life - health status Arms A and C o To evaluate - number of bleeds (both for treated bleeds and all bleeds) over time • To evaluate the overall safety of prophylactic emicizumab • To characterize the exposure of prophylactic emicizumab;Primary end point(s): Number of bleeds over time;Timepoint(s) of evaluation of this end point: Over 24 weeks or discontinuation of study participation, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1-4. Over 24 weeks or discontinuation of study participation, whichever occurs first 5-6. At Weeks 24 and 48 7-12. Up to the end of the study (estimated to be approximately 108 weeks after the first enrolled patient) 13. Upon starting RO5534262 • Every week during Weeks 1-4 • Every 2 weeks during Weeks 5-8 • Every 4 weeks during Weeks 9-24 • Every 8 weeks during Weeks 25-48 • Every 12 weeks thereafter while on RO5534262, until the end of the study;Secondary end point(s): 1.Number of treated bleeds (treated and not treated) over time 2.Number of spontaneous bleeds over time 3.Number of joint bleeds over time 4.Number of target joint bleeds over time 5.Quality of Life questionnaires 6.Health status questionnaire 7.Incidence and severity of adverse events 8.Incidence and severity of thromboembolic events 9.Incidence of adverse events leading to drug discontinuation 10.Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events 11.Incidence and severity of thrombotic microangiopathy 12.Incidence of anti- emicizumab antibodies 13.Plasma concentrations of emicizumab | — |
Countries
Australia, Costa Rica, France, Germany, Italy, Japan, Korea, Republic of, New Zealand, Poland, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed