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Study of PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Male Chinese Subjects With Hemophilia A

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ClinicalTrials.gov Identifier: NCT02461992
Recruitment Status : Completed
First Posted : June 3, 2015
Results First Posted : June 15, 2016
Last Update Posted : September 7, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE June 1, 2015
First Posted Date  ICMJE June 3, 2015
Results First Submitted Date  ICMJE May 9, 2016
Results First Posted Date  ICMJE June 15, 2016
Last Update Posted Date September 7, 2016
Study Start Date  ICMJE July 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2016)
  • Maximum Plasma FVIII Activity (Cmax) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
  • Area Under the Plasma FVIII Activity-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
  • Area Under the Plasma FVIII Activity-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
  • Clearance (CL) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Volume of Distribution at Steady-State (Vss) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state.
  • Terminal Phase Rate Constant (Kel) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile.
  • Terminal Elimination Half-Life (t1/2) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    Terminal half-life is the time measured for the plasma concentration to decrease by one half.
  • Mean Residence Time (MRT) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method.
  • Incremental Recovery (INCREC) [ Time Frame: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose ]
    Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight.
Original Primary Outcome Measures  ICMJE
 (submitted: June 1, 2015)
FVIII activity [ Time Frame: 72hr ]
To characterize single dose pharmacokinetic profile of FVIII activity after administration of Xyntha in male Chinese subjects with hemophilia A
Change History Complete list of historical versions of study NCT02461992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2015)
adverse events [ Time Frame: 72hr ]
To assess the safety and tolerability of a single dose of Xyntha in male Chinese subjects with hemophilia A
Current Other Pre-specified Outcome Measures
 (submitted: May 9, 2016)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 28 ]
    An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
  • Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [ Time Frame: Baseline up to Day 4 ]
    The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, RBC morphology, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine drug screening, FVIII inhibitor assay, FVIII activity, prothrombin time [PT], activated partial thromboplastin time [APTT], anti-human immunodeficiency virus [HIV] 1, hepatitis C virus antibody [HCVAb], HAVAb, HBsAg, HBsAb, HBcAb). Only parameters which met abnormality criteria are reported.
  • Number of Participants With Potentially Clinically Significant Vital Signs Findings [ Time Frame: Baseline up to Day 4 ]
    Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <50 beats per minute (bpm), >=30 bpm increase from baseline, or >25 bpm decrease from baseline; systolic blood pressure (SBP) <90 milliliters of mercury (mmHg), >=30 mmHg increase from baseline, or >=30 mmHg decrease from baseline; diastolic blood pressure (DBP) <50 mmHg, >=20 mmHg increase from baseline, or >=20 mmHg decrease from baseline.
  • Number of Participants With Positive FVIII Inhibitor Activity at Day 4 [ Time Frame: Day 4 ]
    As with all FVIII products, participants using Xyntha were monitored for the development of FVIII inhibitors. Values >= 0.6 Bethesda Unit (BU) per mL were considered positive results.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Male Chinese Subjects With Hemophilia A
Official Title  ICMJE An Open-label, Single Dose Pharmacokinetic Study Of Xyntha (Moroctocog Alfa (Af-cc), Recombinant Factor Viii) In Male Chinese Subjects With Hemophilia A
Brief Summary An open-label, single dose pharmacokinetic study of Xyntha (Moroctocog Alfa (AF-CC), Recombinant Factor VIII) in male Chinese subjects with hemophilia A
Detailed Description The purpose of this study is to obtain pharmacokinetic profiles of FVIII:C after Xyntha administration in Chinese patients with severe hemophilia A, which is in support of the continued registration of Xyntha in China
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Hemophilia A
Intervention  ICMJE Drug: Intravenous infusions of Xyntha
A single dose 50IU/kg dose of Xyntha administered by intravenous infusion within 10 minutes on Day 1
Study Arms  ICMJE Experimental: Intravenous infusion of Xyntha
observation arm
Intervention: Drug: Intravenous infusions of Xyntha
Publications * Liu H, Wu R, Hu P, Sun F, Xu L, Liang Y, Nepal S, Qu PR, Huard F, Korth-Bradley JM. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A. Clin Ther. 2017 Jul;39(7):1313-1319. doi: 10.1016/j.clinthera.2017.05.344. Epub 2017 Jun 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 28, 2015)
13
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2015)
12
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:

  1. Male Chinese subjects 6 years or older (weight >20 kg) with severe hemophilia A (factor VIII activity <1%) previously treated with > 150 exposure days to any FVIII-containing products.
  2. Subjects should not have received an infusion of any FVIII products for at least 3 days (at least 72 hours) before the administration of Xyntha on Day 1.
  3. Subjects must be in a non bleeding state before the administration of Xyntha on Day 1.
  4. Evidence of a personally or legally acceptable representative (legally acceptable representative is only applicable to pediatric subjects) signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

  1. Current FVIII inhibitor or history of FVIII inhibitor (defined as > upper limit of normal (ULN) of the local reporting laboratory).
  2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or clinical findings at Screening.
  3. Diagnosed with any other bleeding disorder in addition to hemophilia A.
  4. Documented Human Immunodeficiency Virus (HIV).
  5. Subjects anticipating elective surgery or other invasive procedure within 1 month following study entry.
  6. Treatment with immunomodulatory therapy within 30 days or 5 half lives whichever is longer, prior to study entry or planned use for the duration of study participation.
  7. Subjects with known hypersensitivity to the active substance or to any of the excipients of Xyntha.
  8. Subjects with a known hypersensitivity to Chinese Hamster Ovary cell (CHO cell) proteins.
  9. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary: significant hepatic or renal impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN, or total bilirubin >2 x ULN or serum creatinine >2 x ULN), prothrombin time >1.5 x ULN, platelet count <80,000 L. Subjects with Gilbert's disease may be enrolled.
  10. Unwilling or unable to follow the terms of the protocol.
  11. Any condition which may compromise the subject's ability to comply with and/or perform study related activities or that poses a clinical contraindication to study participation, in the opinion of the investigator or sponsor.
  12. A positive urine drug screen.
  13. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine, 12 ounces (360 mL) of beer, or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
  14. Treatment with an investigational drug within 30 days or 5 half lives preceding Day 1, whichever is longer.
  15. Screening supine blood pressure 140 mm Hg (systolic) or 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is 140 mm Hg (systolic) or 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.
  16. Screening supine 12 lead ECG demonstrating QTcF >450 or a QRS interval >120 msec msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject's eligibility.
  17. Blood donation (excluding plasma donations) of approximately 500 mL or more within 56 days prior to dosing.
  18. History of sensitivity to heparin or heparin induced thrombocytopenia.
  19. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
  20. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
  21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  22. Subjects with history of infection within 1 week prior to study entry.
  23. Male subjects with partners currently pregnant and male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02461992
Other Study ID Numbers  ICMJE B1831082
2015-003685-88 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2016

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