Pharmacokinetic Study of SCT800 in Previously Treated Patients With Hemophilia A

Study Overview
=================
Brief Summary
-----------------
Participants will be assigned to A or B groups with a scale of 1:1 based on a prospectively randomized treatment-sequence assignment, i.e. infuse SCT800 followed by Xyntha (group A), or the alternate sequence (group B). All participants who completed the SCT800HA1 study will enter the efficacy and safety study (Protocol No.: SCT800HA3).

Official Title
-----------------
Pharmacokinetic Comparison of SCT800 (B-domain Deleted Recombinant Factor VIII) With Xyntha in Previously Treated Patients With Hemophilia A: a Phase I, Open-label, Randomized, Crossover Study

Conditions
-----------------
Hemophilia A

Intervention / Treatment
-----------------
* Biological: SCT800
* Biological: Xyntha


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 12 to 65 years old; The activity of the coagulation factor VIII (FVIII:C) ≤2%, and was previously treated with FVIII concentrate(s) for a minimum of 50 exposure days (EDs) prior to study entry Non-bleeding state (No clinical manifestations of active hemorrhage); Negative assays for FVIII inhibitors (<0.6 BU/mL); The platelet count is normal； Normal prothrombin time or INR ≤1.5； Given informed consent Exclusion Criteria: Hypersensitivity to recombinant coagulation factor VIII concentrate or any of the excipients ;allergic to heterologous proteins (e.g. murine, bovine or hamster origin); Family history or history of FVIII inhibitors (≥0.6 Bethesda Units [BU] mL-1); Received an infusion of any FVIII for on-demand therapy or prophylaxis within 4 days prior to study entry (including rFVIII, plasma-derived factor VIII [pdFVIII], cryoprecipitate and whole blood); Significant hepatic or renal impairment (ALT and AST ≥2×ULN; BUN and Cr≥2×ULN); HIV seropositive; Abnormal hemostasis from causes other than hemophilia A； Patients with severe heart disease, including myocardial infarction, heart failure (III or higher level); Patients who received any anticoagulant or antiplatelet therapy within one week (including NSAIDs) or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials; Alcoholism, drug abuse, mental disorders and mental retardation; Elective surgery planned during the process of study; Patients who previously participated in the other clinical trials prior to study entry; The patient or parent/legal guardian is unable or unwilling to sign an informed consent form or to comply with the requirements of clinical protocol; Other conditions confirmed by the researchers, resulting in that patients are unable to benefit from clinical observation;

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>a single dose administration of SCT800 followed by Xyntha (50 IU.kg-1, based upon the manufacturer's labeled potency) | Biological: SCT800<br> <br> * Other names: Recombinant human coagulation factor VIII;Biological: Xyntha<br> <br> * Other names: Antihemophilic Factor (Recombinant), Plasma/Albumin-Free;|
| Experimental: Group B<br>a single dose administration of Xyntha followed by SCT800(50 IU.kg-1, based upon the manufacturer's labeled potency) | Biological: SCT800<br> <br> * Other names: Recombinant human coagulation factor VIII;Biological: Xyntha<br> <br> * Other names: Antihemophilic Factor (Recombinant), Plasma/Albumin-Free;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Recovery (K-value) | One-stage aPTT Assay | 1hour after the end of the infusion | 
| Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUClast) | One-stage aPTT Assay | 48 hours after the end of the infusion | 
| Elimination Phase Half-life (t1/2) | One-stage aPTT Assay | 48 hours after the end of the infusion | 
| Factor VIII (FVIII) Clearance (CL) | One-stage aPTT Assay | 48 hours after the end of the infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC∞) | One-stage aPTT Assay | 48 hours after the end of the infusion | 
| FVIII Maximum Plasma Concentration (Cmax) | One-stage aPTT Assay | 3 hours after the end of the infusion | 
| Mean Residence Time (MRT) | One-stage aPTT Assay | 48 hours after the end of the infusion | 
| Volume of Distribution at Steady State (Vss) | One-stage aPTT Assay | 48 hours after the end of the infusion | 
| Incidence of inhibitors |  | 72 hours after the end of the infusion | 
| AEs related to SCT800 during treatment and observation of the clinical study |  | 48 hours after the end of the infusion |