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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hemophilia A	Biological: PF-05280602	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia

MedlinePlus related topics: Hemophilia

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	24
Study Start Date:	December 2011
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Biological: PF-05280602 4.5 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 2	Biological: PF-05280602 9.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 3	Biological: PF-05280602 18.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 4	Biological: PF-05280602 30.0 micrograms per kilogram of PF-05280602, IV infusion, single dose

Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439971

Contacts

Contact: Pfizer CT.gov Call Center

1-800-718-1021

Locations

United States, Connecticut
Pfizer Investigational Site	Recruiting
New Haven, Connecticut, United States, 06511
United States, Illinois
Pfizer Investigational Site	Recruiting
Chicago, Illinois, United States, 60612
United States, Kentucky
Pfizer Investigational Site	Recruiting
Louisville, Kentucky, United States, 40202
United States, Ohio
Pfizer Investigational Site	Recruiting
Cincinnati, Ohio, United States, 45229
United States, Oregon
Pfizer Investigational Site	Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Pfizer Investigational Site	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Pfizer Investigational Site	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Belgium
Pfizer Investigational Site	Recruiting
Bruxelles, Belgium, B-1070
Bulgaria
Pfizer Investigational Site	Recruiting
Sofia, Bulgaria, 1612
Hungary
Pfizer Investigational Site	Recruiting
Budapest, Hungary, 1083
Italy
Pfizer Investigational Site	Not yet recruiting
Castelfranco Veneto, Treviso, Italy, 31033
Pfizer Investigational Site	Recruiting
Milano, Italy, 20122
Pfizer Investigational Site	Recruiting
Palermo, Italy, 90127
Pfizer Investigational Site	Recruiting
Vicenza, Italy, 36100
New Zealand
Pfizer Investigational Site	Recruiting
Christchurch, South Island, New Zealand, 8140
Pfizer Investigational Site	Recruiting
Christchurch, New Zealand, 8011
United Kingdom
Pfizer Investigational Site	Recruiting
London, United Kingdom, NW3 2QG
Pfizer Investigational Site	Recruiting
Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01439971 History of Changes
Other Study ID Numbers:	B3051001
Study First Received:	August 26, 2011
Last Updated:	May 1, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Phase 1
Safety
Pharmacokinetic
Pharmacodynamic

Additional relevant MeSH terms:

Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders

Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013