Evaluation of SCT800 in Prophylaxis Therapy on Previous Treated Patients With Severe Hemophilia A

A Multicenter, Open, Single Arm Evaluation of the Efficacy, Safety and Pharmacokinetics of Recombinant Human Coagulation FVIII (SCT800) in Prophylaxis Therapy on Patients With Severe Hemophilia A Who Had Previously Treated With FVIII.

This study is a multi-center, open-label, single-arm trial to evaluate the efficacy,safety and pharmacokinetics of SCT800 in regular prophylaxis and perioperative treatment in patients (≥12 years old) with severe hemophilia A who have been previously treated with coagulation factor VIII(FVIII:C) . This study includes two phases: the screening period and prophylaxis period.Prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered once every other day or three times per week starting from V1 and prophylaxis with SCT800 shall continue for 24 consecutive weeks.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: Recombinant Human Coagulation FVIII

Detailed Description

After subjects pass screening, prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered once every other day or three times per week for 6 months. Subjects shall receive FVIII intravenous injection treatment at the study site or at home. During the study prophylaxis treatment period, subjects should return for visit every four weeks, namely for Visit (V) 2 (4 weeks ± 4 days), Visit 3 (8 weeks ± 4 days), Visit 4 (12 weeks ± 4 days), Visit 5 (16 weeks ± 7 days), Visit 6 (20 weeks ± 7 days), Visit 7 (24 weeks ± 7 days) and end-of-treatment (EOT) visit (+ 14 days). Of which, blood collection shall be carried out during the screening period and in V1, V2, V4, V7 and the EOT visit for FVIII inhibitor assay; blood collection shall be carried out before and after the completion of SCT800 infusion in V1, V4 and V7 for incremental in-vivo recovery (IVR) assay.

FVIII:C activity shall be monitored before injection and 15minutes(min), 30min, 1h, 3h, 6h, 9h, 12h, 24hours(h), 28h, 32h and 48h after injection at V1 and V7. Then pharmacokinetics parameters (incremental in-vivo recovery, t1/2 etc.) of SCT800 shall be calculated and evaluated.

5 subjects may receive elective surgical treatment within the prophylaxis treatment period (after the first drug administration in day 0).

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Aged ≥12 years old and ≤65 years old;
• Male patients who are clinically diagnosed with severe (laboratory tested FVIII:C <1%) hemophilia A, including historical FVIII:C <1%;
• Previously received FVIII treatment (prophylactic or bleeding treatment), have the relevant records and are verified to have accumulated exposures days( EDs) ≥150 days;
• The bleeding treatment records of at least 3 months before screening can be obtained;
• Negative FVIII inhibitor assay results (laboratory tested Nijmegen-Bethesda assay result <0.6 BU(Bethesda unit)/mL);
• The prothrombin time is normal or international normalized ratio (INR) ≤1.5; 7. Platelet count ≥100 × 109/L;

Exclusion Criteria:

• Known allergy to recombinant coagulation factor VIII concentrate or any excipient; known allergy to bovine, rodent or hamster bovine;
• Has a history or family history of blood coagulation factor VIII inhibitor;
• Clinical liver function test (glutamic-pyruvic transaminase, glutamic-pyruvic transaminase) ≥ three times the upper limit of normal (ULN) or clinical kidney function test (blood urea nitrogen, creatinine) ≥ three times the ULN;
• Patients clinically diagnosed with active Hepatitis B or Hepatitis C;
• Patients with other coagulation dysfunction diseases in addition to hemophilia A;
• Patients with severe heart disease, including myocardial infarction and cardiac dysfunction of class III or above;
• Patients who previously experienced intracranial bleeding;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recombinant Human Coagulation FVIII; Participant receivedSCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.	Drug: Recombinant Human Coagulation FVIII; Participant received SCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.; Other Names: SCT800

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate	Annualized Bleeding Rate（ABR） can be calculated using the following formula: Number of bleeding events in efficacy evaluation period/(number of days in treatment period/365.25)	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized joint bleeding rate	Annualized joint bleeding rate（AJBR） can be calculated using the following formula: Number of joint bleeding events during efficacy evaluation period/(number of days in treatment period/365.25).	up to 24 weeks
Bleeding event treatment efficacy	The investigator shall evaluate the hemostatic effect after the treatment of every bleeding event of subjects based on a four-point scale(excellent, good, moderate, not relieved).	up to 24 weeks
FVIII incremental in-vivo recovery	Incremental recovery is determined as the peak factor level recorded in the first hour after infusion and is reported as [IU/ml]/[IU/kg]	Predose within 30 min，15 min±2 min、1 hour±5 min.
Elimination Half Life	t1/2; One-stage aPTT Clotting Assay and Chromogenic Assay	Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.
Clearance	CL; One-stage aPTT Clotting Assay and Chromogenic Assay	Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.
Area Under the Curve to the Last Measurable Timepoint	AUClast;One-stage aPTT Clotting Assay and Chromogenic Assay	Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of FVIII inhibitors	The Nijmegen-Bethesda assay shall be used to monitor the production of FVIII inhibitors during the trial.	up tp 24 weeks

Collaborators and Investigators

• Sponsor: Sinocelltech Ltd.
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Parexel; Q2 Solutions
• Investigators: Principal Investigator: Renchi Yang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): January 16, 2020
• Study Completion (Actual): January 16, 2020

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 20, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

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
• Other Study ID Numbers: SCT800-A 302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No