China ADVATE PTP Study

Hemophilia A Clinical Trial

Official title:

Study to Evaluate Efficacy and Safety of ADVATE in the Treatment of Previously Treated Patients With Hemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02170402
• Other study ID #: 061301
• Status: Completed
• Phase: Phase 4
• Start date: June 26, 2014
• Est. completion date: May 31, 2016

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess efficacy, safety and pharmacokinetics of ADVATE in the treatment and prevention of bleeding episodes (BEs)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: May 31, 2016
• Est. primary completion date: May 31, 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

Main Inclusion Criteria:

• Ethnic Chinese

• is of any age

• has a documented diagnosis of severe or moderately severe hemophilia A (congenital FVIII deficiency: baseline Factor VIII (FVIII) = 2%)

• has documented and verified >50 exposure days (EDs) to FVIII (recombinant or plasma derived)

• is receiving on-demand treatment with FVIII at the time of enrolment in this study

• has negative history of inhibitor development

• is HIV negative or HIV positive with stable disease and CD4+ count = 200 cells per mm^3

• is negative for Hepatitis C virus (HCV); Or participant is HCV positive with chronic stable hepatitis as assessed by investigator

Main Exclusion Criteria:

• has prior history of hypersensitivity or anaphylaxis associated with receipt of FVIII

• is diagnosed with other bleeding disorder(s) other than hemophilia A, including but not limited to thrombocytopenia (platelet count < 100000 /mL)

• has been exposed to an investigational product (IP) within 30 days prior to the screening visit or is scheduled to participate in another clinical study involving an IP or investigational device during participation in the study

• is planned, or likely to have surgery during the study period

• has end-stage renal failure or evidence of a severe or uncontrolled systemic disease as judged by the investigator

• has active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 5 times the upper limit of normal)

• has clinical or laboratory evidence of severe liver impairment including (but not limited to) a recent & persistent international normalized ratio (INR) >1.4, and/or the presence of splenomegaly and/or significant spider angioma on physical exam, and/or a history of esophageal hemorrhage or documented esophageal varices

• is a family member of the investigator or site staff

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• Octocog alfa (recombinant human coagulation factor VIII)
Part 1: Pharmacokinetic (PK) analysis - Subset of 24 participants Part 2: On-demand treatment regimen Part 3: Prophylaxis treatment regimen

Locations

Country	Name	City	State
China	Beijing Children's Hospital Affiliated to Capital University of Medical Sciences	Beijing
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Peking Union Medical College Hospital	Dongcheng	Beijing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of College of Medicine, Zhengjiang University	Hangzhou	Zhejiang
China	Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Hospital of Blood Disease, Chinese Academy of Medical Sciences	Tianjin
China	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of reduction in annualized bleed rate (ABR) during prophylactic treatment compared to ABR during on demand treatment	Computed as: {[median ABR on-demand - median ABR prophylaxis]÷[median ABR on-demand]}*100%; The ABR, will be assumed to have a negative binomial distribution. The 2 treatment regimens (on-demand and prophylaxis) will be compared in terms of mean ABR within a generalized linear model framework (with a logarithmic link function which is the default for the negative binomial distribution), accounting for the fixed effect of study arm and the follow-up time (in years) as an offset. Ratios between treatment means (95% CI) will be estimated within this model.	12 months
Secondary	Number of units per kg body weight of ADVATE required to resolve a bleeding episode (BE)		12 months
Secondary	Number of infusions of ADVATE required to resolve a bleeding episode (BE)		12 months
Secondary	Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor)		12 months
Secondary	Annualized bleeding episode rates (ABR) according to bleed type and bleed etiology summarized by treatment regimen	Bleed types and etiologies summarized by treatment regimen (prophylaxis, on-demand) including: Joint bleeds; Non-joint bleeds; Spontaneous bleeds; Traumatic bleeds; Target joint bleeds	12 months
Secondary	Inhibitor incidence	Inhibitor incidence in: Previously treated patients (PTPs) with previous 51-150 exposure days (EDs) to Factor VIII (FVIII); PTPs with previous >150 EDs to FVIII	13 months
Secondary	Adverse events according to relatedness, seriousness, and severity		13 months
Secondary	Area under the plasma concentration/time curve from time 0 to infinity	Computed as AUC0-t + Ct/ ?z, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration, and ?z is the terminal rate constant	Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Secondary	Mean Residence Time (MRT)	Computed as AUMC0-8 / AUC0-8 - TI/2, where AUMC0-8 will be determined in a similar manner as AUC0-8 and TI represents infusion duration [hour]	Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Secondary	Clearance (CL)	Computed as Dose/ AUC0-8	Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Secondary	Incremental Recovery (IR) at Cmax	Computed as: (Cmax - Cpre-infusion)/Dose, where Cmax will be determined as the highest concentration achieved within one hour after infusion	Within 30 minutes prior to the start of the infusion, and within 1 hour post-infusion
Secondary	Elimination phase half-life	Computed as: ln2/ ?z. ?z will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2	Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Secondary	Volume of distribution at steady state (Vss)	Computed as: CL * MRT	Within 30 minutes prior to the start of the infusion through 48 hours post-infusion