Evaluate Efficacy and Safety of Recombinant Factor VIII （rFVIII）Treatment of Severe or Moderately Severe Hemophilia A

Hemophilia A Clinical Trial

Official title:

An Open-Label, Multicenter Evaluation of Safety, Pharmacokinetics, and Efficacy of rFVIII in the Prevention and Treatment of Bleeding Episodes in Chinese With Hemophilia A

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02930317
• Other study ID #: CTTQ-NXBYZ
• Status: Recruiting
• Phase: Phase 3
• First received: September 9, 2016
• Last updated: October 11, 2016
• Start date: August 2016
• Est. completion date: December 2017

Study information

• Verified date: October 2016
• Source: Jiangsu Chia-tai Tianqing Pharmaceutical Co.,Ltd
• Contact: Lei Zhang, Doctor
• Email: zlpumc[@]hotmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Efficacy, Safety and Pharmacokinetics Study of a rFVIII in Chinese subjects with Hemophilia A.To assess efficacy and safety of rFVIII administered as treatment and as on-demand therapy in adult and adolescent (12-65 years) patients with severe or moderately severe Hemophilia A. To determine the pharmacokinetic (PK) parameters of rFVIII.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of hemophilia A

• Age of 12 Years to 65 Years,Diagnosis of severe (defined as <1% FVIII:C documented in medical records) or moderately severe(defined as 1%-5% FVIII:C documented in medical records) hemophilia A .Subjects who(Age of 18 Years to 65 Years) have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product;The Callan (Age of 12 Years to 17) have received FVIII products and have had>50 EDs a FVIII product.

• Subjects without a past history of, or current no factor VIII inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer Lower than the laboratory's normal range or <0.6 BU/mL (BU:Bethesda Units ).

• Liver and kidney function in accordance with the standard

• Subjects of childbearing potential should agree to use and utilize an adequate method of contraception throughout treatment and for at least 28 days after study is stopped

• Evidence of a personally or legally acceptable representative (legally acceptable representative is only applicable to Callan subjects) signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

• The part one of subjects subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures; Subjects must be in a non bleeding state before the administration of rFVIII on Day 1; Subjects should not have received an infusion of any FVIII products for at least 3 days (at least 72 hours) before the administration of rFVIII on Day 1

Exclusion Criteria:

• Current FVIII inhibitor or history of FVIII inhibitor (>0.6 BU/mL )

• Diagnosed with any bleeding disorder in addition to hemophilia

• Documented Human Immunodeficiency Virus (HIV)

• Subjects anticipating elective surgery or other invasive procedure within 1 month following study entry

• Treatment with an immunomodulatory within 30 days or 5 half lives preceding Day 1, whichever is longer

• Subjects with known hypersensitivity to the active substance or to any of the excipients of rFVIII. Subjects with a known hypersensitivity to Chinese Human embryonic kidney cell proteins

• Subjects with severe anemia requiring blood transfusion

• Subjects with significant hepatic or renal impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x ULN, or total bilirubin >2 x ULN or serum creatinine >2 x ULN), prothrombin time >1.5 x ULN, platelet count <80,000 µL. History of sensitivity to heparin or heparin induced thrombocytopenia or others thrombocytopenia

• Patients with heart surgery history requires anticoagulation therapy; Subjects with severe heart disease, including myocardial infarction or heart failure Grade 3 or higher(NYHA Classification)

• Blood pressure unable to be controlled ideally(systolic pressure>150 mmHg,diastolic pressure>90 mmHg)

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• Recombinant Factor VIII (50 IU/kg)

• Recombinant Factor VIII (On-demand treatment)

Locations

Country	Name	City	State
China	Anhui provincial hospital	Hefei	Anhui
China	Ruijin Hospital Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Second hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Chia-tai Tianqing Pharmaceutical Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.	Up to 28 days after last dose	Yes
Primary	Recovery rate = (change actual value of rFVIII activity before and after infusion )/(change expected value of rFVIII activity before and after infusion)*100%		At 15 and 60 minutes after the first infusion	No
Primary	Investigator Hemostatic Efficacy Assessment 6 Hours Post Infusion	The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions).	6 hours post infusion	No
Secondary	The proportion of subjects who achieved the expected effect after the first infusion of the rFVIII		At 15 minutes after the first infusion	No
Secondary	change actual value of rFVIII activity before and after infusion levels		At 15 and 60 minutes after the first infusion	No
Secondary	FVIII Maximum Plasma Concentration		Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration		Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose	No
Secondary	Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours		Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose	No
Secondary	Terminal Elimination Half-Life (t1/2)		Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose	No