A Phase 1 Safety, Pharmacokinetics And Pharmacodynamics Study Of PF-05280602, A Recombinant Factor VIIa Variant (813d), In Adult Subjects With Hemophilia A Or B

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01439971
First received: August 26, 2011
Last updated: October 2, 2014
Last verified: October 2014

August 26, 2011
October 2, 2014
December 2011
October 2014   (final data collection date for primary outcome measure)
  • Incdence of subjects wtih treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of of subjects with treatment emergent hemophilia adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of subjects with treatment emergent serious adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- blood pressure [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's ECG [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's physical examination [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Tropin T levels [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Troponin T levels [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of an immune response [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Anti-Thrombin III [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Tissue Factor Pathway Inhibitor [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their fibrinogen [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- weight [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- temperature [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- respiration rate [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- pulse rate [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of subjects wtih treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of of subjects with treatment emergent hemophilia adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of subjects with treatment emergent serious adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Withdrawals due to treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Withdrawals due to treatment emergent hemophilia events [ Time Frame: Within 60 Day of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for hematology [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for hematology [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for chemistry [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for chemistry [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for urinalysis [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for urinalysis [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for platelet count [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for platelet count [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Anti-Thrombin III [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Tissue Factor Pathway Inhibitor [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for C-Reactive Protein [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for C-Reactive Protein [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their Anti-Thrombin III [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's vital signs- blood pressure [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's ECG [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's physical examination [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their Tropin T levels [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects who develop signs of an immune response [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their Tissue Factor Pathway Inhibitor [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their fibrinogen [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's vital signs- weight [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's vital signs- temperature [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's vital signs- respiration rate [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Clinically significant changes from baseline in patient's vital signs- pulse rate [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their platelet count [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with treatment emergent hemophilia adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with treatment emergent serious adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01439971 on ClinicalTrials.gov Archive Site
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Cmax [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, area under the curve (AUC last) [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, terminal half-life [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, recovery [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Pharmacodynamic (Hematologic) activity as measured by the Prothrombin Time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the activated partial thrombinplastin time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the thrombin antithrombin complexes [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the prothrombin fragments 1+2 [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by D-Dimers [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by thrombin generation [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, area under the curve (AUC inf) [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, mean residence time [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Vss [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, clearance [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Tmax [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Cmax [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, area under the curve (AUC) [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, half-life [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, recovery [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Pharmacodynamic (Hematologic) activity as measured by the Prothrombin Time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the activated partial thrombinplastin time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the thrombin antithrombin complexes [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the prothrombin fragments 1+2 [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by D-Dimers [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by thrombin generation [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Phase 1 Safety, Pharmacokinetics And Pharmacodynamics Study Of PF-05280602, A Recombinant Factor VIIa Variant (813d), In Adult Subjects With Hemophilia A Or B
An Ascending Single Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Pf-05280602, A Recombinant Factor Viia Variant (813d), In Adult Hemophilia A And B Subjects With Or Without Inhibitors

This study hypothesizes that the study drug, PF-05280602 (at the selected doses) will be safe to administer to subjects with severe Hemophilia A or B with or without inhibitors and will demonstrate evidence of hemostatic activity. This is supported by the preclinical findings in hemophilic animal models.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Hemophilia A
  • Biological: PF-05280602
    4.5 micrograms per kilogram of PF-05280602, IV infusion, single dose
  • Biological: PF-05280602
    9.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
  • Biological: PF-05280602
    18.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
  • Biological: PF-05280602
    30.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
  • Experimental: 1
    Intervention: Biological: PF-05280602
  • Experimental: 2
    Intervention: Biological: PF-05280602
  • Experimental: 3
    Intervention: Biological: PF-05280602
  • Experimental: 4
    Intervention: Biological: PF-05280602
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
December 2014
October 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male subjects 18 to <65 years old with severe hemophilia A or B with or without inhibitors to FVIII or FIX.
  • Subjects is willing and able to comply with the mandatory washout periods prior to screening and prior to dosing and through 48 hours post dosing. At screening this includes a washout of FIX for 96 hours and FVIII for 72 houts. At dosing this includes a washout of FIX for 96 hours and FVIII and other hemostatic agents for 72 hours through 48 hours post dosing.
  • Subjects must agree and commit to using a a highly effective method of birth control from the time of screening through four weeks after study drug administration.

Exclusion Criteria:

  • Presence of a bleeding disorder in addition to hemophilia A or B.
  • Regular, concomitant therapy with immunomodulating drugs (eg, intravenous immunoglobulin, and routine systemic corticosteroids).
  • History of coronary artery disease, thrombolic disease or diagnosis of prothrombic disorder.
Male
18 Years to 64 Years
No
Contact: Pfizer CT.gov Call Center 1-800-718-1021
United Kingdom,   Italy,   New Zealand,   United States,   Turkey,   Belgium,   South Africa,   Hungary
 
NCT01439971
B3051001, 2011-002170-23
Yes
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
October 2014

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