Hemophilia A MedDRA version: 19.0 Level: LLT Classification code 10018938 Term: Haemophilia A (Factor VIII) System Organ Class: 100000004850 MedDRA version: 19.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850
Conditions
Sponsors
Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Aged >=12 years •Body weight >= 40 kg at screening •Have severe congenital hemophilia A or hemophilia A with FVIII inhibitors Patients without FVIII inhibitors ( 0.6 BU/mL since ITI •For patients to be enrolled into PK run-in cohort: Current episodic treatment (FVIII or bypassing agents) at the time of entry into this study and documentation of details of episodic treatment for at least 24 weeks prior to entry into this study •For patients to be enrolled into the expansion cohort: Documentation of details of prophylactic or episodic treatment and the number of bleeding episodes for at least 24 weeks prior to entry into this study. For patients on an episodic regimen, >= 5 bleeds in the prior 24 weeks, regardless of inhibitor status •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: •Inherited or acquired bleeding disorder other than hemophilia A •Ongoing or planned ITI therapy; patient in whom ITI has failed will be eligible with a 72-hour washout period prior to the first emicizumab administration •History of illicit drug or alcohol abuse within 48 weeks prior to screening •Previous (within the last 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease •Other conditions (e.g., certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis •History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection •Known HIV infection with cluster of differentiation 4 (CD4) counts = 200 cell/µL will be permitted) •Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy •Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study or pose an additional unacceptable risk in administering study drug to the patient •Women with a positive serum pregnancy test or pregnant/lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: There is no formal hypothesis testing in this study: Expansion phase: Efficacy objectives •To evaluate the efficacy of prophylactic emicizumab in maintaining adequate control of bleeding •To evaluate the efficacy in reducing the number of joint bleeds over time, target joint bleeds over time, all bleeds over time •To evaluate the health-related quality of life of patients Safety Objectives •To evaluate the overall safety of emicizumab given Q4W in patients with hemophilia A Pharmacokinetic Objective •To characterize the pharmacokinetics of multiple Q4W doses of 6mg/kg emicizumab ; Secondary Objective: Please note, there is no formal hypothesis testing in this study Run-in phase objectives: •To investigate the pharmacokinetics (PK) of emicizumab after single and multiple (every 4 weeks [Q4W]) subcutaneous (SC) administration of 6 milligram per Kilogram (mg/kg) •To assess the safety and tolerability of emicizumab after Q4W SC administration of 6 mg/kg •To explore the prophylactic effect of emicizumab in maintaining adequate control of bleeding •To investigate the effect of emicizumab on pharmacodynamic (PD) markers including (but not limited to) activated partial thromboplastin time, thrombin generation, and factor VIII (FVIII) activity ; Primary end point(s): Efficacy: (Expansion phase) 1.Number of bleeds over time 2.Number of joint bleeds over time 3.Number of target joint bleeds over time 4.HRQoL of patients according to Haem-A-QoL (>= 18years) or Haemo-QoL_SF (ages 12-17 years) scores after 24 weeks 5.EQ-5D-5L scores after 24 weeks 6.Number of bleeds over time | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PK endpoints: (Run-in and expansion phase) 1.Time to maximum observed plasma concentration 2.Area under the plasma concentration (AUC)-time curve over a dosing interval 3.Pre-dose (trough) plasma concentrations of emicizumab (Expansion phase) Safety endpoints: (Run-in and expansion phase) 4.Incidence and severity of adverse events 5.Incidence and severity of thromboembolic events 6.Changes in physical examination findings and vital signs 7.Incidence of laboratory abnormalities 8.Incidence and severity of injection-site reactions 9.Incidence of adverse events leading to drug discontinuation 10.Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events 11.Incidence of clinically significant levels of anti-emicizumab antibodies 12.Incidence of de novo development of FVIII inhibitors (non-inhibitor population) Efficacy endpoint (Run-in phase): 13.Maintaining adequate control of bleeding Pharmacodynamics (Run-in and expansion phase) 14.PD marker analyses ; Timepoint(s) of evaluation of this end point: 1-3. Day 1 until study completion (24 weeks after emicizumab stop OR transfer to other emicizumab trial OR withdrawal) 4-13. Up to study completion (24 weeks after emicizumab stop OR transfer to other emicizumab trial OR withdrawal) 14. Day 1 until study completion (24 weeks after emicizumab stop OR transfer to other emicizumab trial OR withdrawal) | — |
Countries
Belgium, Japan, Poland, Spain
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed