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China ADVATE PTP Study

Sponsor
Baxalta now part of Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT02170402
Collaborator
(none)
82
Enrollment
11
Locations
1
Arm
23.2
Actual Duration (Months)
7.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

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)

Condition or Disease Intervention/Treatment Phase
  • Biological: Octocog alfa (recombinant human coagulation factor VIII)
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
82 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Study to Evaluate Efficacy and Safety of ADVATE in the Treatment of Previously Treated Patients With Hemophilia A
Actual Study Start Date :
Jun 26, 2014
Actual Primary Completion Date :
May 31, 2016
Actual Study Completion Date :
May 31, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Previously Treated Patients (PTPs)

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

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
Other Names:
  • ADVATE

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of reduction in annualized bleed rate (ABR) during prophylactic treatment compared to ABR during on demand treatment [12 months]

      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

    1. Number of units per kg body weight of ADVATE required to resolve a bleeding episode (BE) [12 months]

    2. Number of infusions of ADVATE required to resolve a bleeding episode (BE) [12 months]

    3. Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor) [12 months]

    4. Annualized bleeding episode rates (ABR) according to bleed type and bleed etiology summarized by treatment regimen [12 months]

      Bleed types and etiologies summarized by treatment regimen (prophylaxis, on-demand) including: Joint bleeds Non-joint bleeds Spontaneous bleeds Traumatic bleeds Target joint bleeds

    5. Inhibitor incidence [13 months]

      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

    6. Adverse events according to relatedness, seriousness, and severity [13 months]

    7. Area under the plasma concentration/time curve from time 0 to infinity [Within 30 minutes prior to the start of the infusion through 48 hours post-infusion]

      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

    8. Mean Residence Time (MRT) [Within 30 minutes prior to the start of the infusion through 48 hours post-infusion]

      Computed as AUMC0-∞ / AUC0-∞ - TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration [hour]

    9. Clearance (CL) [Within 30 minutes prior to the start of the infusion through 48 hours post-infusion]

      Computed as Dose/ AUC0-∞

    10. Incremental Recovery (IR) at Cmax [Within 30 minutes prior to the start of the infusion, and within 1 hour post-infusion]

      Computed as: (Cmax - Cpre-infusion)/Dose, where Cmax will be determined as the highest concentration achieved within one hour after infusion

    11. Elimination phase half-life [Within 30 minutes prior to the start of the infusion through 48 hours post-infusion]

      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

    12. Volume of distribution at steady state (Vss) [Within 30 minutes prior to the start of the infusion through 48 hours post-infusion]

      Computed as: CL * MRT

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Peking Union Medical College Hospital Dongcheng Beijing China 100730
    2 Fujian Medical University Union Hospital Fuzhou Fujian China 350001
    3 Cangzhou Central Hospital Cangzhou Hebei China 061001
    4 Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital Wuhan Hubei China 430022
    5 Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University Wuhan Hubei China 430030
    6 Xiangya Hospital Central South University Changsha Hunan China 410008
    7 The First Affiliated Hospital of Soochow University Suzhou Jiangsu China 215006
    8 The First Affiliated Hospital of College of Medicine, Zhengjiang University Hangzhou Zhejiang China 310003
    9 Beijing Children's Hospital Affiliated to Capital University of Medical Sciences Beijing China 100045
    10 Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China 200025
    11 Hospital of Blood Disease, Chinese Academy of Medical Sciences Tianjin China 300020

    Sponsors and Collaborators

    • Baxalta now part of Shire

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Baxalta now part of Shire
    ClinicalTrials.gov Identifier:
    NCT02170402
    Other Study ID Numbers:
    • 061301
    First Posted:
    Jun 23, 2014
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 1, 2021
    Additional relevant MeSH terms:
    Hemophilia A
    Factor VIII

    Study Results

    No Results Posted as of May 3, 2021