Pharmacokinetic Study of SCT800 in Previously Treated Patients With Hemophilia A

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

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).

Study Overview

• Status: Unknown
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: SCT800; Biological: Xyntha

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Centre-South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Sinocelltech Ltd.
• Investigators: Principal Investigator: Xie lan Zhao, PhD, Xiangya Hospital of Centre-South University, Changsha, China

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: August 30, 2016
• First Posted (Estimate): September 2, 2016

Study Record Updates

• Last Update Posted (Estimate): September 2, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: SCT800HA1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No