Back to resultsChina ADVATE PTP Study
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Octocog alfa (recombinant human coagulation factor VIII)
Sponsored by
About this trial
This is an interventional prevention trial for Hemophilia A
Eligibility Criteria
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
Sites / Locations
- Peking Union Medical College Hospital
- Fujian Medical University Union Hospital
- Cangzhou Central Hospital
- Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital
- Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University
- Xiangya Hospital Central South University
- The First Affiliated Hospital of Soochow University
- The First Affiliated Hospital of College of Medicine, Zhengjiang University
- Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
- Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
- Hospital of Blood Disease, Chinese Academy of Medical Sciences
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Previously Treated Patients (PTPs)
Arm Description
PTPs will participate sequentially with: Part 1: Pharmacokinetic parameters of ADVATE measured in subset of 24 participants, consisting of: 12 adults (>12 years of age) 12 children (≤12 years of age) Part 2: On-demand treatment with ADVATE for 6 months Part 3: Prophylaxis regimen with ADVATE for 6 months
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of units per kg body weight of ADVATE required to resolve a bleeding episode (BE)
Number of infusions of ADVATE required to resolve a bleeding episode (BE)
Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor)
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
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
Adverse events according to relatedness, seriousness, and severity
Area under the plasma concentration/time curve from time 0 to infinity
Computed as AUC0-t + Ct/ λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration, and λz is the terminal rate constant
Mean Residence Time (MRT)
Computed as AUMC0-∞ / AUC0-∞ - TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration [hour]
Clearance (CL)
Computed as Dose/ AUC0-∞
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
Elimination phase half-life
Computed as: ln2/ λz. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2
Volume of distribution at steady state (Vss)
Computed as: CL * MRT
Full Information
NCT ID
NCT02170402
First Posted
June 20, 2014
Last Updated
April 29, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT02170402
Brief Title
China ADVATE PTP Study
Official Title
Study to Evaluate Efficacy and Safety of ADVATE in the Treatment of Previously Treated Patients With Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 26, 2014 (Actual)
Primary Completion Date
May 31, 2016 (Actual)
Study Completion Date
May 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess efficacy, safety and pharmacokinetics of ADVATE in the treatment and prevention of bleeding episodes (BEs)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Previously Treated Patients (PTPs)
Arm Type
Experimental
Arm Description
PTPs will participate sequentially with:
Part 1: Pharmacokinetic parameters of ADVATE measured in subset of 24 participants, consisting of:
12 adults (>12 years of age)
12 children (≤12 years of age)
Part 2: On-demand treatment with ADVATE for 6 months
Part 3: Prophylaxis regimen with ADVATE for 6 months
Intervention Type
Biological
Intervention Name(s)
Octocog alfa (recombinant human coagulation factor VIII)
Other Intervention Name(s)
ADVATE
Intervention Description
Part 1: Pharmacokinetic (PK) analysis - Subset of 24 participants
Part 2: On-demand treatment regimen
Part 3: Prophylaxis treatment regimen
Primary Outcome Measure Information:
Title
Percentage of reduction in annualized bleed rate (ABR) during prophylactic treatment compared to ABR during on demand treatment
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of units per kg body weight of ADVATE required to resolve a bleeding episode (BE)
Time Frame
12 months
Title
Number of infusions of ADVATE required to resolve a bleeding episode (BE)
Time Frame
12 months
Title
Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor)
Time Frame
12 months
Title
Annualized bleeding episode rates (ABR) according to bleed type and bleed etiology summarized by treatment regimen
Description
Bleed types and etiologies summarized by treatment regimen (prophylaxis, on-demand) including:
Joint bleeds
Non-joint bleeds
Spontaneous bleeds
Traumatic bleeds
Target joint bleeds
Time Frame
12 months
Title
Inhibitor incidence
Description
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
Time Frame
13 months
Title
Adverse events according to relatedness, seriousness, and severity
Time Frame
13 months
Title
Area under the plasma concentration/time curve from time 0 to infinity
Description
Computed as AUC0-t + Ct/ λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration, and λz is the terminal rate constant
Time Frame
Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Title
Mean Residence Time (MRT)
Description
Computed as AUMC0-∞ / AUC0-∞ - TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration [hour]
Time Frame
Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Title
Clearance (CL)
Description
Computed as Dose/ AUC0-∞
Time Frame
Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Title
Incremental Recovery (IR) at Cmax
Description
Computed as: (Cmax - Cpre-infusion)/Dose, where Cmax will be determined as the highest concentration achieved within one hour after infusion
Time Frame
Within 30 minutes prior to the start of the infusion, and within 1 hour post-infusion
Title
Elimination phase half-life
Description
Computed as: ln2/ λz. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2
Time Frame
Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Title
Volume of distribution at steady state (Vss)
Description
Computed as: CL * MRT
Time Frame
Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
10. Eligibility
Sex
Male
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Dongcheng
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Fujian Medical University Union Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Name
Cangzhou Central Hospital
City
Cangzhou
State/Province
Hebei
ZIP/Postal Code
061001
Country
China
Facility Name
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Facility Name
Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
Xiangya Hospital Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410008
Country
China
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
The First Affiliated Hospital of College of Medicine, Zhengjiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
City
Beijing
ZIP/Postal Code
100045
Country
China
Facility Name
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Hospital of Blood Disease, Chinese Academy of Medical Sciences
City
Tianjin
ZIP/Postal Code
300020
Country
China
12. IPD Sharing Statement
Learn more about this trial
China ADVATE PTP Study
We'll reach out to this number within 24 hrs