Clinical trial NCT02930317: Evaluate Efficacy and Safety of Recombinant Factor VIII （rFVIII）Treatment of Severe or Moderately Severe Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-10-12
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Recovery rate = (change actual value of rFVIII activity before and after infusion )/(change expected value of rFVIII activity before and after infusion)*100%
timeFrame: At 15 and 60 minutes after the first infusion
measure: Investigator Hemostatic Efficacy Assessment 6 Hours Post Infusion
timeFrame: 6 hours post infusion
Secondary outcomes:
measure: The proportion of subjects who achieved the expected effect after the first infusion of the rFVIII
timeFrame: At 15 minutes after the first infusion
measure: change actual value of rFVIII activity before and after infusion levels
timeFrame: At 15 and 60 minutes after the first infusion
measure: FVIII Maximum Plasma Concentration
timeFrame: Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration
timeFrame: Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose
measure: Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours
timeFrame: Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose
measure: Terminal Elimination Half-Life (t1/2)
timeFrame: Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 6, 9, 24,36,and 48 hours post-dose
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Up to 28 days after last dose
Locations:
city: Hefei
country: China
facility: Anhui provincial hospital
state: Anhui
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Second hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)
state: Tianjin
Study officials:
References: