Severe hemophilia A. Hereditary factor VIII deficiency
Conditions
Interventions
Emicizumab (AryoGen Pharmed Co.), SUBQ, in the following dosing for a total duration of 20 weeks: Initial: 3 mg/kg once weekly for 4 weekso Maintenance: 6 mg/kg once every 4 weeks unti
Sponsors
AryoGen Pharmed Company
Eligibility
Sex/Gender
Male
Age
2 Years to No maximum
Inclusion criteria
Inclusion criteria: Male patients with 2 years of age and older at the time of signing the informed consent form Willingness for signing and having signed the informed consent form by the patient, or the patient's legally authorized representative for patients under the legal age Diagnosed with severe hemophilia A (endogenous FVIII < 1% [1 IU/dL]) Annualized bleeding rate (ABR) = 12, without receiving any treatment for hemophilia and before starting emicizumab, based on documented records History of inhibitors, based on documented records Having adequate bone marrow and organ function:- Plt = 80,000 cells/µL - Hb = 8 g/dL- eGFR = 30 mL/min- ALT and AST = 5 × ULN- Serum total bilirubin = 1.5 × ULN, or up to 3 × ULN if direct (conjugated) bilirubin is within the normal range Hemlibra®-treated patients (having documented emicizumab dosing) will be selected to closely align with the intervention group in terms of demographic characteristics, including age, and if possible, weight. These patients must meet the inclusion criteria of the intervention group. Also, the patients must have received = 12 weeks maintenance therapy, without any deviation from dosing beyond this period:? Planned 28-day interval (± 7 days)All eligibility criteria for these patients will be evaluated by the investigator, and upon their approval, the patient will be enrolled in the study.
Exclusion criteria
Exclusion criteria: History of other coagulation disorders except for hemophilia A 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 Participants with other conditions (for example [e.g.], certain autoimmune diseases) that may increase the risk of bleeding or thrombosis based on the investigator's judgment Acute hemorrhagic state within a week before recruitment Treatment with aPCC, within 72 hours before recruitment Infection with HIV, HCV or HBV Use of systemic immunosuppressive drugs or immunomodulators (e.g., interferon or rituximab) at enrolment. (In participants treated with these drugs, the intervention will not be performed until 5-7 half-lives have passed.) Participants who are at high risk for thrombotic microangiopathy (TMA; e.g., have a previous medical or family history of TMA), based on the investigator's judgment Participants receiving anti-platelet or anti-coagulant agents or any medications that increase bleeding tendency, which may interfere with the study results; e.g., nonsteroidal anti-inflammatory drugs (NSAIDs) with significant impact on coagulation, anticoagulants (warfarin, non-vitamin K antagonist oral anticoagulants [NOACs], etc.), antiplatelets (aspirin, clopidogrel, ticagrelor, etc.), selective serotonin reuptake inhibitors (SSRIs), and other supplements with impact on coagulation (e.g., ginseng, ginkgo biloba, vitamin E, omega 3, etc.) 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, preclude the participant's safe participation in and completion of the study or interpretation of the study results History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection Planned surgery during the study Receipt of other investigational drug concurrently or within last 30 days or five half-lives before recruitment, whichever is shorter Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (e.g., physical, psychological, or mental problems) Patients receiving Hemlibra® who meet any of the exclusion criteria specified for the intervention group, or who, in the investigator’s opinion, have conditions that, or whose data use and/or repeated blood sampling, may interfere with the study outcome results or compromise patient safety, will not be enrolled in the study.All eligibility criteria for these patients will be evaluated by the investigator, and upon their approval, the patient will be enrolled in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Emicizumab (manufactured by AryoGen Pharmed Co.) trough concentration at steady state (Ctrough,ss) assessed at Weeks 16 and 20, compared with Ctrough,ss in historical cohort patients at steady state. Annualized Bleeding Rate (ABR) in subjects receiving emicizumab (AryoGen Pharmed Co.) during the 24 weeks of study, compared with the ABR in the historical cohort. Bleeding requiring treatment (bleeding due to trauma, surgery, and spontaneous bleeding) is an event in which coagulation factors are prescribed to treat signs or symptoms of bleeding (such as pain, swelling, etc.). Bleeding that occurs at the same site from the first sign of bleeding to 72 hours after the last treatment for bleeding is considered a bleeding episode. Any injection to treat bleeding that is performed 72 hours after the previous injection is considered the first injection to treat new bleeding at the same site. Any bleeding in a different location, regardless of the time since the last injection, is considered a separate bleeding. Any bleeding reported by the patient during medical history taking will be recorded, even if they did not receive any treatment. Maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration–time curve (AUC0-t) plasma concentration assessed between Week 16 and Week 20 at the following timepoints: before emicizumab administration at Week 16; and 8 hours, 3 days, 7 days, 14 days, and 28 days after administration at Week 16, compared with historical cohort patients at steady state. Timepoint: Between Weeks 16 to 20 (PK parameters), during the 24 weeks of study period (annualized bleeding rate). Method of measurement: Blood sampling (PK parameters), recording the bleeding events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of adverse events during all scheduled visits in comparison with the historical cohort. Timepoint: During all scheduled visits. Method of measurement: Clinical monitoring.;Assessment of immunogenicity (anti-drug antibody (ADA) development). Timepoint: Screening, Visits 8 and 10. Method of measurement: Enzyme-Linked Immunosorbent assay (ELISA). | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactDr Hamidreza Kafi
Orchid Pharmed Co.
Outcome results
None listed