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An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01486927
First received: November 19, 2011
Last updated: November 17, 2014
Last verified: November 2014

November 19, 2011
November 17, 2014
February 2012
November 2014   (final data collection date for primary outcome measure)
  • Treatment success [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Subjects will receive treatment for any bleeding episode and the investigator will rate the efficacy of the treatment based on a four point rating scale "excellent, good, moderate or poor/no response".
  • Treatment success during the peri-operative surgical sub-study [ Time Frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) ] [ Designated as safety issue: No ]
    Subjects will receive pre-treatment with rFVIII prior to major surgery. The investigator will rate the efficacy of the treatment based on a four point rating scale of "excellent, good, moderate or poor/no response".
  • Inhibitor formation to FVIII [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Number of subjects who develop inhibitors to FVIII
  • Annualized spontaneous bleeding rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The annualized bleeding rate for subjects taking the prophylaxis treatment regimen
  • Treatment success [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]
    Subjects will receive treatment for any bleeding episode and the investigator will rate the efficacy of the treatment based on a four point rating scale "excellent, good, moderate or poor/no response".
  • Treatment success during the peri-operative surgical sub-study [ Time Frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) ] [ Designated as safety issue: No ]
    Subjects will receive pre-treatment with rFVIII prior to major surgery. The investigator will rate the efficacy of the treatment based on a four point rating scale of "excellent, good, moderate or poor/no response".
  • Inhibitor formation to FVIII [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]
    Number of subjecs who develop inhibitors to FVIII
Complete list of historical versions of study NCT01486927 on ClinicalTrials.gov Archive Site
  • AUC0-t [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUC0-t of a single infusion of octocog alfa and CSL627
  • AUC0-∞ [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUC0-∞ of a single infusion of octocog alfa and CSL627
  • Percent of area extrapolated [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Percent of area extrapolated of a single infusion of octocog alfa and CSL627
  • Cmax [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Cmax of a single infusion of octocog alfa and CSL627
  • Tmax [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Tmax of a single infusion of octocog alfa and CSL627
  • Elimination constant [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Elimination constant of a single infusion of octocog alfa and CSL627
  • Half-life (t1/2) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Half-life (t1/2) of a single infusion of octocog alfa and CSL627
  • AUMC0-∞ [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    AUMC0-∞ of a single infusion of octocog alfa and CSL627
  • Mean residence time (MRT) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Mean residence time (MRT) of a single infusion of octocog alfa and CSL627
  • Clearance (Cl) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Clearance (Cl) of a single infusion of octocog alfa and CSL627
  • Volume of distribution at steady-state (Vss) [ Time Frame: Before infusion and at up to 12 time points within 5 days of infusion ] [ Designated as safety issue: No ]
    Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and CSL627
  • Proportion of bleeding episodes [ Time Frame: Assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 visit ] [ Designated as safety issue: No ]
    Proportion of bleeding episodes requiring one, 2, 3 or > 3 infusions of CSL627 to achieve hemostasis
  • Incremental recovery [ Time Frame: At 30 minutes after infusion ] [ Designated as safety issue: No ]
    Incremental recovery of a single infusion of octocog alfa and CSL627
  • Annualized bleeding rate for total bleeds, traumatic bleeds, and joint bleeds [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The annualized bleeding rate of total bleeds, traumatic bleeds and joint bleeds, for subjects taking the prophylaxis treatment regimen
  • AUC0-t [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    AUC0-t of a single infusion of octocog alpha and CSL627
  • AUC0-∞ [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    AUC0-∞ of a single infusion of octocog alpha and CSL627
  • Percent of area extrapolated [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Percent of area extrapolated of a single infusion of octocog alpha and CSL627
  • Cmax [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Cmax of a single infusion of octocog alpha and CSL627
  • Tmax [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Tmax of a single infusion of octocog alpha and CSL627
  • Elimination constant [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Elimination constant of a single infusion of octocog alpha and CSL627
  • Half-life (t1/2) [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Half-life (t1/2) of a single infusion of octocog alpha and CSL627
  • AUMC0-∞ [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    AUMC0-∞ of a single infusion of octocog alpha and CSL627
  • Mean residence time (MRT) [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Mean residence time (MRT) mean residence time (MRT) of a single infusion of octocog alpha and CSL627
  • Clearance (Cl) [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Clearance (Cl) of a single infusion of octocog alpha and CSL627
  • Volume of distribution at steady-state (Vss) [ Time Frame: 1/2, 1, 4, 8, 10, 24, 28, 48 and 72 hours ] [ Designated as safety issue: No ]
    Volume of distribution at steady-state (Vss) of a single infusion of octocog alpha and CSL627
  • Proportion of bleeding episodes [ Time Frame: Assessed at Months 1, 2, 3, 4, 5, 6, 9, and 12 visit ] [ Designated as safety issue: No ]
    Proportion of bleeding episodes requiring one, 2, 3 or > 3 infusions of CSL627 to achieve hemostasis
Not Provided
Not Provided
 
An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A
A Phase I/III Open-label, Multicenter, Crossover Safety, Efficacy and Pharmacokinetic Study of Recombinant Coagulation Factor VIII (rFVIII) Compared to Recombinant Human Antihaemophilic Factor VIII (rFVIII; INN: Octocog Alfa) in Subjects With Hemophilia A, and a Repeat PK, Safety and Efficacy Study

This is an open-label, non-randomized, efficacy, safety and PK study comparing octocog alfa and CSL627. The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK section (Part 3) including a surgical sub-study for subjects enrolled in Parts 2 and 3.

Not Provided
Interventional
Phase 2
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia A
Biological: Recombinant Factor VIII (rFVIII)
In Part 1 of the study, subjects will receive a single infusion of 50 IU/kg of octocog alfa followed by a single infusion of 50 IU/kg CSL627; each infusion will be preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects will receive infusions of CSL627 to prevent or treat bleeding episodes, at a dose and frequency determined by their study doctor (based on the subject's underlying bleeding phenotype).
Other Name: CSL627
Experimental: Recombinant Factor VIII (rFVIII)
Intervention: Biological: Recombinant Factor VIII (rFVIII)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
104
November 2014
November 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of severe hemophilia A defined as <1% FVIII:C documented in medical records.
  • Males between 18 and 65 years of age (Parts 1 and 2).
  • Males between 12 and 65 years of age (Part 3).
  • Subjects who 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
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

  • Any history of or current FVIII inhibitors
  • Any first order family history of FVIII inhibitors
  • Use of an Investigational Medicinal Product within 30 days prior to the first CSL627 administration.
  • Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of CSL627 or reference product.
  • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
  • Any known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
  • Platelet count < 100,000/µL at screening.
  • HIV positive subjects with a CD4 count < 200/mm3, in their medical history or at screening if available results are older than one year. (HIV positive subjects may participate in the study and antiviral therapy are permitted, at the discretion of the Investigator).
  • Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
  • Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values > 5 times (x) the upper limit of normal (ULN) at Screening.
  • Subjects with serum creatinine values > 2 x ULN at Screening.
  • Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to Day 1.
  • Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Day 1.
Male
12 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Canada,   Czech Republic,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Malaysia,   Netherlands,   Philippines,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   Sweden,   Ukraine,   United Kingdom
 
NCT01486927
CSL627_1001, 2011-002393-23
Not Provided
CSL Behring
CSL Behring
Not Provided
Study Director: Program Director CSL Behring
CSL Behring
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP