Hemophilia A, Severe
Conditions
Keywords
Congenital hemophilia A, Prophylaxis, On-demand, FVIII concentrate, Hemophilia A
Brief summary
This is a prospective, multicenter, open-label study to assess efficacy, safety, pharmacokinetics (PK), and immunogenicity of human plasma-derived Factor VIII (FVIII) in previously treated patients (PTPs) with severe hemophilia A. Overall, 55 male PTPs aged 12 to 65 years old with a FVIII level of \< 1% and at least 150 treatment exposure days (EDs) with a previous FVIII product will be enrolled. Patients will receive SKP-0141 at a dose of 25 to 50 IU/kg every second day or 3 times per week for at least 50 EDs and/or 6 months from the start of prophylactic treatment. Efficacy of SKP-0141 will be primarily evaluated in bleeding prophylaxis with annualized bleeding rate from start of treatment and until end of treatment (Visit 10).
Interventions
BIOLOGICALSKP-0141
Human plasma-derived coagulation factor VIII concentrate
Sponsors
SK Plasma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* A patient or parent/legal guardian who is capable of giving signed informed consent * Patients assigned male at birth and must be 12 to 65 years old at the time of Screening * Diagnosis of severe congenital hemophilia A, defined as an FVIII level of \<1% as documented in the patient's medical records at the time of Screening * Patients who have received or are currently receiving plasma-derived and/or recombinant FVIII products and have had at least 150 EDs with a FVIII product * Patients who can produce viable sperm and have a partner of childbearing potential must agree to take appropriate contraceptive measures consistently during the study, starting at Screening and until 30 days after the end of study
Exclusion criteria
* Any history of or current FVIII inhibitors or any first order family history of FVIII inhibitors in terms of detectable FVIII inhibitors (ie, ≥0.6 Bethesda Units \[BU\]) using the Nijmegen-modification of the Bethesda assay * Any known congenital or acquired coagulation disorder other than the congenital hemophilia A * Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction, and arterial embolus within 3 months prior to Visit 1 * Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Visit 1 * Has been tested positive for HIV with a CD4+ count ≤200/μL at Screening (if available, hepatitis B surface antigen, or hepatitis C virus antibodies, and/or positive hepatitis B virus deoxyribonucleic acid/HCV ribonucleic acid at Screening * Platelet count \<100 000/μL at Screening * Patients with serum aspartate aminotransferase or serum alanine aminotransferase values \>5 × the upper limit of normal or serum creatinine values \>2 × ULN at Screening * Patients who are currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment within 3 months prior to Visit 1 * Use of any other investigational medicinal product, cryoprecipitate, whole blood, or plasma within 30 days or 5 half-lives prior to Visit 1 * Known or suspected hypersensitivity to any FVIII product or their excipients * Has a physical, medical, or psychological condition, that in the opinion of the PI, may interfere with the evaluation of the study. * Are study site personnel directly affiliated with this study and their immediate families
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized bleeding rate | Up to 25 weeks | Efficacy of SKP-0141 in bleeding prophylaxis in previously treated patients with severe hemophilia A based on the number of bleeding episodes per year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak plasma concentration (Cmax) | At 1 week and 25 weeks | Maximum plasma concentration of SKP-0141 in previously treated patients with severe hemophilia A |
| Consumption of SKP-0141 required for prophylaxis | Up to 25 weeks | Dose of SKP-0141 injections (IU/kg/year and IU/kg/month) required for prophylaxis in previously treated patients with severe hemophilia A |
| Consumption of SKP-0141 required for on-demand treatment | Up to 25 weeks | Dose/number of SKP-0141 injections (IU/kg/bleed) required for treatment of bleeding episodes in previously treated patients with severe hemophilia A |
| Hemostatic response | Up to 25 weeks | Efficacy of SKP-0141 for the treatment of breakthrough bleeding episodes using a 4-point scale in previously treated patients with severe hemophilia A |
| Time to reach peak plasma concentration (Tmax) | At 1 week and 25 weeks | Time to reach peak plasma concentration of SKP-0141 in previously treated patients with severe hemophilia A |
| Area under the plasma concentration versus time curve (AUC) | At 1 week and 25 weeks | Area under the plasma concentration versus time curve in previously treated patients with severe hemophilia A |
| Half-life (T1/2) | At 1 week and 25 weeks | Half-life of SKP-0141 in previously treated patients with severe hemophilia A |
| Total plasma clearance (CL) | At 1 week and 25 weeks | Total plasma clearance of SKP-0141 in previously treated patients with severe hemophilia A |
| Elimination constant (Kel) | At 1 week and 25 weeks | Elimination rate constant of SKP-0141 in previously treated patients with severe hemophilia A |
| Mean residence time (MRT) | At 1 week and 25 weeks | Mean residence time in vivo of SKP-0141 in previously treated patients with severe hemophilia A |
| Incremental in vivo recovery (IVR) | At 1 week and 25 weeks | Incremental in vivo recovery (IVR) in previously treated patients with severe hemophilia A |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 26 weeks | Incidence of treatment-emergent adverse events in previously treated patients with severe hemophilia A |
| Incidence of serious adverse events (SAEs) | Up to 26 weeks | Incidence of serious adverse events in previously treated patients with severe hemophilia A |
| Incidence of adverse events of special interest (AESIs) | Up to 26 weeks | Incidence of adverse events of special interest in previously treated patients with severe hemophilia A |
| Incidence of adverse events (AEs) | Up to 26 weeks | Incidence of adverse events in previously treated patients with severe hemophilia A |
| Incidence of clinically significant changes | Up to 25 weeks | Safety and tolerability of SKP-0141 in previously treated patients with severe hemophilia A based on the incidence of clinically significant changes from baseline in safety laboratory evaluations (hematology, serum chemistry, and urinalysis), vital signs (pre- and post-injection), physical examinations, and ECG |
| Incidence of FVIII inhibitor formation | Up to 25 weeks | Immunogenicity of SKP-0141 from incidence of FVIII inhibitor formation (≥0.6 Bethesda Units) calculated using the Nijmegen-modified Bethesda assay in previously treated patients with severe hemophilia A |
| Volume of distribution (Vd) | At 1 week and 25 weeks | Volume of distribution of SKP-0141 in previously treated patients with severe hemophilia A |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hemostatic response in surgical prophylaxis | Perioperatively/Periprocedurally | Hemostatic response (efficacy) of SKP-0141 in surgical prophylaxis in previously treated patients with severe hemophilia A |
Contacts
Primary ContactByung Nam Chung
Backup ContactGaram Kim, M.S.
Outcome results
None listed