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China ADVATE PTP Study

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ClinicalTrials.gov Identifier: NCT02170402
Recruitment Status : Completed
First Posted : June 23, 2014
Last Update Posted : October 23, 2017
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

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
Hemophilia A Biological: Octocog alfa (recombinant human coagulation factor VIII) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Non-Randomized
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
Study Start Date : June 2014
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016


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 Name: ADVATE




Primary Outcome Measures :
  1. Percentage of reduction in annualized bleed rate (ABR) during prophylactic treatment compared to ABR during on demand treatment [ Time Frame: 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) [ Time Frame: 12 months ]
  2. Number of infusions of ADVATE required to resolve a bleeding episode (BE) [ Time Frame: 12 months ]
  3. Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor) [ Time Frame: 12 months ]
  4. Annualized bleeding episode rates (ABR) according to bleed type and bleed etiology summarized by treatment regimen [ Time Frame: 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 [ Time Frame: 13 months ]

    Inhibitor incidence in:

    1. Previously treated patients (PTPs) with previous 51-150 exposure days (EDs) to Factor VIII (FVIII)
    2. PTPs with previous >150 EDs to FVIII

  6. Adverse events according to relatedness, seriousness, and severity [ Time Frame: 13 months ]
  7. Area under the plasma concentration/time curve from time 0 to infinity [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion ]
    Computed as: CL * MRT



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02170402


Locations
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China, Beijing
Peking Union Medical College Hospital
Dongcheng District, Beijing, China, 100730
China, Fujian
Fujian Medical University Union Hospital
Fuzhou, Fujian, China, 350001
China, Hebei
Cangzhou Central Hospital
Cangzhou, Hebei, China, 061001
China, Hubei
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital
Wuhan, Hubei, China, 430022
Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University
Wuhan, Hubei, China, 430030
China, Hunan
Xiangya Hospital Central South University
Changsha, Hunan, China, 410008
China, Jiangsu
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
China, Zhejiang
The First Affiliated Hospital of College of Medicine, Zhengjiang University
Hangzhou, Zhejiang, China, 310003
China
Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
Beijing, China, 100045
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China, 200025
Hospital of Blood Disease, Chinese Academy of Medical Sciences
Tianjin, China, 300020
Sponsors and Collaborators
Baxalta now part of Shire
Investigators
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Study Director: Leon Rozen, MD Baxter Healthcare Corporation

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Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02170402     History of Changes
Other Study ID Numbers: 061301
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: October 23, 2017
Last Verified: July 2016
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants